Background: Reports of probiotic consumption on athletes’ performance are debatable due to their equivocal results. There is a need for more evidence on the effects of probiotic intake on psychological state and fitness level. Thus, this study determined the effects of daily probiotic consumption on competitive anxiety, perceived stress and mood among university badminton players, besides their fitness like aerobic capacity, strength, speed, leg power and agility.
Methods: Thirty university badminton players aged from 19 to 22 years old were randomly divided equally into two groups, where the probiotic group (PG; n = 15) received a drink that contained L. casei Shirota (SHIROTA strain) (3 x 1010 CFU) and placebo group (CG; n = 15) a placebo drink for six weeks. Anxiety, stress and mood levels were determined using the CSAI-2R, PSS and BRUMS questionnaires, respectively. Fitness levels were measured by subjecting the players to 20-m shuttle runs (aerobic capacity), handgrips (muscular strength), vertical jumps (leg power), 40-m dash (speed) and T-test (agility). The Student’s t-test (p < 0.05) was used to determine the differences between PG and CG players.
Results: After six weeks, the anxiety and stress levels of PG players significantly decreased by 16% (p < 0.001) and 20% (p < 0.001), respectively, but there were no significant changes detected in CG players. Supplementation of probiotics also improved aerobic capacity in PG players by 5.9% (p < 0.001) but did not influence the speed, strength, leg power and agility.
Conclusions: Probiotics supplementation showed improved aerobic capacity and relieve anxiety and stress. However, further studies need to be carried out to determine the mechanisms through which probiotic intake produces these effects.
The study conducted in Vietnam investigated the effects of the probiotic L. casei Shirota (SHIROTA strain) L. casei Shirota (SHIROTA strain) on immune profiles and intestinal microbial translocation among children infected with human immunodeficiency virus (HIV). This prospective study included 60 HIV-infected children-including 31 HIV positive children without antiretroviral therapy and 29 HIV positive children who received antiretroviral therapy for a period of 3.5 years and 20 children without HIV infection . All children were given fermented milk containing L. casei Shirota (SHIROTA strain) (6.5 × 10⁸ cfu) daily for 8 weeks. Before and after L. casei Shirota (SHIROTA strain) ingestion, blood samples were collected for virological, immunological, and bacteriological analyses.
After L. casei Shirota (SHIROTA strain) ingestion, peripheral CD4⁺ T-cell and specific Th2 counts significantly increased in both HIV-infected groups; Th17 counts increased in all three groups; regulatory T-cell counts decreased in the ART(+) and HIV(-) groups; activated CD8⁺ cells decreased from 27.5% to 13.2% (p < 0.001) in HIV positive children; and plasma HIV load decreased slightly but significantly among HIV(+) children. No serious adverse events occurred. These findings suggest that short-term L. casei Shirota (SHIROTA strain) ingestion is a safe supportive approach with immunological and virological benefits in HIV-infected children.
Aim: To determine the immune response of healthy adults to the ingested Probiotic.
Methods: Daily ingestion of a probiotic drink containing L. casei Shirota (SHIROTA strain) (1.3 x 1010 live cells) by healthy adults for (i) 4-weeks LcS, (ii) 6-weeks discontinuation of LcS, and (iii) final 4-weeks of LcS, was investigated.
Results: There was a significant increase in expression of the T-cell activation marker CD3+ CD69+ in ex vivo unstimulated blood cells at weeks 10 and 14 and a significant increase in the Natural Killer (NK) cell marker CD3+ CD16/56+ in ex vivo unstimulated blood cells at weeks 4, 10 and 14. Expression of the NK cell activation marker CD16/56+ CD69+ in ex vivo unstimulated blood cells was 62% higher at week 10 and 74% higher at week 14. Intracellular staining of IL-4 in ex vivo unstimulated and PMA/ionomycin-stimulated CD3+ β7+ integrin blood cells was significantly lower at week 10 and 14. Intracellular staining of IL-12 in ex vivo unstimulated and LPS-stimulated CD14+ blood cells was significantly lower at weeks 4, 10 and 14. Intracellular staining of TNF-α in LPS-stimulated CD14+ blood cells was significantly lower at weeks 4, 10 and 14. Mucosal salivary IFN-γ, IgA1 and IgA2 concentrations were significantly higher at week 14 but L. casei Shirota (SHIROTA strain) did not affect systemic circulating influenza A-specific IgA or IgG and tetanus specific IgG antibody levels.
Conclusions: In addition to the decrease in CD3+ β7+ integrin cell IL-4 and a CD14+ cell anti-inflammatory cytokine profile, at week 14 increased expression of activation markers on circulating T cells and NK cells and higher mucosal salivary IgA1 and IgA2 concentration indicated a secondary boosting effect of LcS.
Aim: To evaluate the effect of Lactobacillus casei strain Shirota-fermented milk (LcS-FM) on the incidence of Upper Respiratory Tract Infections (URTI) in healthy idle aged office workers.
Methods: Study was conducted in 96 healthy middle-aged office workers in the age group of 30 – 49 years. The office workers consumed LcS-Fermented Milk containing 1.0 × 1011 L. casei Shirota (SHIROTA strain) bacteria or control milk (CM) once daily for 12 weeks during the winter season. URTI episodes were evaluated by a physician via a questionnaire of URTI symptoms.
Results: The results of the study showed that the incidence of URTI’s during the intervention period were significantly lower in the LcS-FM group as compared to the CM group (22.4 vs. 53.2 %, P = 0.002). The time to-event analysis showed that the LcS-FM group had a significantly higher URTI-free rate than the CM group over the test period (log-rank test: χ2 11.25, P = 0.0008). The cumulative number of URTI episodes and cumulative days with URTI symptoms per person was lower in the LcS-FM group, and the duration per episode was also shorter. There was no reduction in NK cell activity in peripheral blood mononuclear cells and no increase in salivary cortisol levels in the LcS-FM group.
Conclusions: The conclusion of the study suggests that the daily intake of fermented milk with LcS may reduce the risk of URTI’s in healthy middle-aged office workers, probably through modulation of the immune system.
Aim: The efficacy of probiotic L. casei Shirota (SHIROTA strain) in reducing incidence of ventilator-associated pneumonia (VAP) in medical patients who received mechanical ventilation at Siriraj Hospital was evaluated.
Method: A prospective, randomized, open-label controlled trial was conducted on 150 adult hospitalized patients in medical wards who were on mechanical ventilation for 72 hours or longer: The patients were randomized to the probiotic group or the control group. The patients in the probiotic group received 80 ml of a probiotic fermented milk drink containing 8 billion L. casei Shirota (SHIROTA strain) for oral care after having standard oral care once daily and additional 80 ml of the aforementioned fermented dairy product was given via enteral feeding once daily. The primary outcomes were incidence of VAP and incidence rate of VAP episodes per 1,000 ventilator-days. The secondary outcomes were length of hospital stay, mortality at day 28 and 90, incidence of diarrhea, and presence of resistant bacteria in oropharyngeal and rectal swab samples taken from the patients at baseline, day 7 and day 28 after enrollment.
Results: The baseline characteristics of the patients in the probiotic group (75) and the control group (75) were not significantly different. The patients in the probiotic group were less likely to develop VAP compared with the control group (24% vs. 29.3%, p = 0.46). The incidence rates of VAP in the probiotic and control groups were 22.64 and 30.22 episodes per 1,000 ventilator-days, respectively (p = 0.37). A trend of lower prevalence of resistant bacteria cultured from oropharyngeal swabs in the probiotic group than that in the control group was observed. Overall 28 and 90-day mortality and length of hospital stay of the patients in both groups was not significantly different.
Conclusions: Administration of probiotic containing L. casei Shirota (SHIROTA strain) resulted in a tendency to reduce the incidence of VAP and colonization with resistant bacteria in oropharyngeal cavity without significant effects on mortality and length of hospital stay.
PURPOSE:There is growing evidence that probiotics
confer health benefits to the host by modulating immune function,
especially in older people, where immunosenescence is a feature even of
healthy ageing. The aim of this study was to investigate the effect of a
probiotic drink containing L. casei Shirota (SHIROTA strain)
on immune function in a healthy non-immunocompromised older
METHODS: Thirty healthy old volunteers were recruited into a randomized placebo-controlled, single-blind crossover study. The volunteers were supplemented with the probiotic drink containing 1.3 × 1010 CFU L. casei Shirota (SHIROTA strain) or skimmed milk per day for 4 weeks, followed by 4 weeks of washout and were crossed over to the other treatment. Peripheral blood and saliva samples were collected at baseline and end of each treatment.
RESULTS: Probiotic consumption was associated with a significant increase in natural killer (NK) cell activity relative to baseline and a significant decrease in the mean fluorescence intensity of CD25 expression in the resting T cells compared with placebo. Additionally, there was a trend towards an increased ratio of IL-10 to IL-12 relative to baseline after L. casei Shirota (SHIROTA strain) intake.
CONCLUSIONS: Consumption of a probiotic drink containing L. casei Shirota (SHIROTA strain) improved NK cell activity and tended to produce a more anti-inflammatory cytokine profile in an older population.
Probiotics have already proven beneficial effects in the treatment of several intestinal infections, but the underlying mechanisms how the probiotics can affect responses of porcine IPEC-J2 enterocytes to oxidative stress remained to be elucidated. The immunomodulatory effect of five bacterial strains (Lactobacillus plantarum 2142, L. casei Shirota (SHIROTA strain) ,Bifidobacterium animalis subsp. lactis BB-12, Bacillus amyloliquefaciens CECT 5940 and Enterococcus faecium CECT 4515) on 1 mM peroxide-triggered upregulation of interleukin (IL)-8 and tumor necrosis factor alpha (TNF-α) level was screened by q RT-PCR. Our data revealed that spent culture supernatant (SCS) of L. plantarum 2142 had significant lowering effect on IL-8 and TNF-α level with concomitant promoting activity on protective Hsp70 gene expression. According to our results, lactic acid (racemic, D: - and L: -lactic acid) and acetic acid produced by lactobacilli had no protective effect in quenching upregulation of proinflammatory cytokines. Furthermore, L. plantarum 2142-specific supernatant peptides were detected by gel electrophoresis and capillary zone electrophoresis.
CONTEXT:It is of great importance to evaluate the
safety of probiotics in dysregulated immune conditions, as probiotics
can possibly modulate immune functions in the host.
OBJECTIVE:We tried to confirm the safety of using L. casei Shirota (SHIROTA strain) to help prevent autoimmunity in the central nervous system.
METHODS: We used two chronic experimental autoimmune encephalomyelitis (EAE) models, a relapse and remission type EAE model in SJL/J mice and a durable type model in C57BL/6 mice. L. casei Shirota (SHIROTA strain) was administered from 1 week before antigen sensitization until the end of the experiments, and neurological symptoms and histopathological changes of the spinal cord were observed. Immunological parameters were also examined in the SJL/J mouse model.
RESULTS:L. casei Shirota (SHIROTA strain) administration did not exacerbate neurological symptoms or histopathological changes of the spinal cord in either model but instead tended to improve neurological symptoms in the SJL/J mouse EAE model. L. casei Shirota (SHIROTA strain) administration transiently upregulated IL-17 production by antigen-stimulated lymphocytes of draining lymph nodes 7 days after sensitization. Enhanced production of IL-10 and an increase in the percentage of CD4(+)CD25(+) T regulatory cells were also observed at the same sites. Strong expression of IL-17 mRNA was detected in the spinal cord of mice that displayed severe neurological symptoms on day 12, but this expression was not enhanced by L. casei Shirota (SHIROTA strain) administration.
CONCLUSION:These results demonstrate that L. casei Shirota (SHIROTA strain) does not exacerbate, but instead may improve EAE depending on the immunization conditions, and that IL-17 responses at peripheral sites may not always result in a worsening of autoimmune diseases.
There is considerable interest in the strain specificity of immune modulation by probiotics. The present study compared the immunomodulatory properties of six probiotic strains of different species and two genera in a human peripheral blood mononuclear cell (PBMC) model in vitro. Live cells of lactobacilli ( Lactobacillus casei Shirota, L. rhamnosus GG, L. plantarum NCIMB 8826 and L. reuteri NCIMB 11951) and bifidobacteria ( Bifidobacterium longum SP 07/3 and B. bifidum MF 20/5) were individually incubated with PBMC from seven healthy subjects for 24 h. Probiotic strains increased the proportion of CD69+ on lymphocytes, T cells, T cell subsets and natural killer (NK) cells, and increased the proportion of CD25+, mainly on lymphocytes and NK cells. The effects on activation marker expression did not appear to be strain specific. NK cell activity was significantly increased by all six strains, without any significant difference between strains. Probiotic strains increased production of IL-1β, IL-6, IL-10, TNF-α, granulocyte-macrophage colony-stimulating factor and macrophage inflammatory protein 1α to different extents, but had no effect on the production of IL-2, IL-4, IL-5 or TNF-β. The cytokines that showed strain-specific modulation included IL-10, interferon-γ, TNF-α, IL-12p70, IL-6 and monocyte chemotactic protein-1. The Lactobacillus strains tended to promote T helper 1 cytokines, whereas bifidobacterial strains tended to produce a more anti-inflammatory profile. The results suggest that there was limited evidence of strain-specific effects of probiotics with respect to T cell and NK cell activation or NK cell activity, whereas production of some cytokines was differentially influenced by probiotic strains.
Dietary probiotics supplementation exerts beneficial health effects. Since cigarette smoking reduces natural killer (NK) activity, we evaluated the effect of L. casei Shirota (SHIROTA strain) L. casei Shirota (SHIROTA strain) intake on NK cytotoxic activity in male smokers. The double-blind, placebo-controlled, randomised study was conducted on seventy-two healthy Italian blue-collar male smokers randomly divided for daily intake of L. casei Shirota (SHIROTA strain) powder or placebo. Before and after 3 weeks of intake, peripheral blood mononuclear cells were isolated and NK activity and CD16 cells' number were assessed. Daily L. casei Shirota (SHIROTA strain) intake for 3 weeks significantly increased NK activity (P < 0.001). The increase in NK activity was paralleled by an increase in CD16 cells (P < 0.001). Before intake, NK cytotoxic activity inversely correlated with the number of cigarettes smoked (R - 0.064). L. casei Shirota (SHIROTA strain) intake prevented the smoke-dependent expected NK activity reduction. The analysis of the distribution of changes in smoke-adjusted NK activity demonstrated that the positive variations were significantly associated with L. casei Shirota (SHIROTA strain) intake, while the negative variations were associated with placebo intake (median value of distributions of differences, 20.98 lytic unit (LU)/10 cells for L. casei Shirota (SHIROTA strain) v. - 4.38 LU/10 cells for placebo, P = 0.039). In conclusion, 3 weeks of daily L. casei Shirota (SHIROTA strain) intake in Italian male smokers was associated with a higher increase in cytotoxic activity and CD16 cells' number in comparison to the placebo intake group.
Probiotics have been reported to be efficacious against cancers, infections, allergies, inflammatory bowel diseases and autoimmune diseases, and it is important to explain how such multifunctional activities are realized. L. casei Shirota (SHIROTA strain) (L. casei Shirota (SHIROTA strain) ) is one of these multifunctional probiotics, and its ability to augment the host immune system has been extensively examined. We have shown that the cell wall structure of this probiotic strain is responsible for potently inducing IL-12 production. In addition, we have recently found that L. casei Shirota (SHIROTA strain) differentially controls the inflammatory cytokine responses of macrophages and T cells in either Peyer's patches or the spleen. Other studies revealed that L. casei Shirota (SHIROTA strain) -induced IL-12 production by macrophages is modified when other bacteria or their cell components are simultaneously present. These findings can provide a theoretical basis for understanding the multifunctional activities of specific probiotics.
Modulation of host immunity is an important potential mechanism by which probiotics confer health benefits. This study was designed to investigate the effects of a probiotic strain, Lactobacillus casei Shirota L. casei Shirota (SHIROTA strain) , on immune function using human peripheral blood mononuclear cells (PBMC) in vitro. In addition, the role of monocytes in L. casei Shirota (SHIROTA strain) -induced immunity was also explored. L. casei Shirota (SHIROTA strain) promoted natural killer (NK) cell activity and preferentially induced expression of CD69 and CD25 on CD8(+) and CD56(+) subsets in the absence of any other stimulus. L. casei Shirota (SHIROTA strain) also induced production of interleukin (IL)-1beta, IL-6, tumour necrosis factor (TNF)-alpha, IL-12 and IL-10 in the absence of lipopolysaccharide (LPS). In the presence of LPS, L. casei Shirota (SHIROTA strain) enhanced IL-1beta production but inhibited LPS-induced IL-10 and IL-6 production, and had no further effect on TNF-alpha and IL-12 production. Monocyte depletion reduced significantly the impact of L. casei Shirota (SHIROTA strain) on lymphocyte activation, cytokine production and natural killer (NK) cell activity. In conclusion, L. casei Shirota (SHIROTA strain) activated cytotoxic lymphocytes preferentially in both the innate and specific immune systems, which suggests that L. casei Shirota (SHIROTA strain) could potentiate the destruction of infected cells in the body. L. casei Shirota (SHIROTA strain) also induced both proinflammatory and anti-inflammatory cytokine production in the absence of LPS, but in some cases inhibited LPS-induced cytokine production. Monocytes play an important role in L. casei Shirota (SHIROTA strain) -induced immunological responses.
The purpose of this study was to examine the effects of a probiotic supplement during 4 mo of winter training in men and women engaged in endurance-based physical activities on incidence of upper respiratory-tract infections (URTIs) and immune markers. Eighty-four highly active individuals were randomized to probiotic (n = 42) or placebo (n = 42) groups and, under double-blind procedures, received probiotic (PRO: L. casei Shirota (SHIROTA strain) [L. casei Shirota (SHIROTA strain) ]) or placebo (PLA) daily for 16 wk. Resting blood and saliva samples were collected at baseline and after 8 and 16 wk. Weekly training and illness logs were kept. Fifty-eight subjects completed the study (n = 32 PRO, n = 26 PLA). The proportion of subjects on PLA who experienced 1 or more weeks with URTI symptoms was 36% higher than those on PRO (PLA 0.90, PRO 0.66; p = .021). The number of URTI episodes was significantly higher (p < .01) in the PLA group (2.1 ± 1.2) than in the PRO group (1.2 ± 1.0). Severity and duration of symptoms were not significantly different between treatments. Saliva IgA concentration was higher on PRO than PLA, significant treatment effect F(1, 54) = 5.1, p = .03; this difference was not evident at baseline but was significant after 8 and 16 wk of supplementation. Regular ingestion of L. casei Shirota (SHIROTA strain) appears to be beneficial in reducing the frequency of URTI in an athletic cohort, which may be related to better maintenance of saliva IgA levels during a winter period of training and competition.
BACKGROUND: Changes in the composition of the gut
microbiota have been implicated in the pathogenesis of allergic
disorders, suggesting beneficial interactions between the intestinal
immune system and specific bacterial strains. Lactobacilli are naturally
present within the complex gastrointestinal microbiota of humans and
they are currently present in many probiotic supplements.
OBJECTIVE: We sought to investigate the role that Lactobacillus casei Shirota L. casei Shirota (SHIROTA strain) may play in modulating seasonal allergic rhinitis (SAR).
METHODS:The study format was double-blinded, placebo-controlled with 10 SAR sufferers in each group. We have documented and compared changes in immune status arising through the daily ingestion of a milk drink with or without live L. casei Shirota (SHIROTA strain) , over a period of 5 months. Pre-, peak- and post-grass pollen season blood samples were collected for determination of plasma total IgE and grass pollen-specific IgG and IgE levels by an enzyme immunoassay. At the same time, cytokine levels were determined by flow cytometric bead array technology following culture of peripheral blood mononuclear cells for 6 days in the presence or absence of specific grass pollen antigens.
RESULTS:Volunteers treated with L. casei Shirota (SHIROTA strain) showed a significant reduction in levels of antigen-induced IL-5, IL-6 and IFN-gamma production compared with volunteers supplemented with placebo. Meanwhile, levels of specific IgG increased and IgE decreased in the probiotic group.
CONCLUSION: Changes in antigen-induced production of cytokines were observed in patients treated with probiotics. These data show that probiotic supplementation modulates immune responses in allergic rhinitis and may have the potential to alleviate the severity of symptoms.
Nine healthy middle-aged and 10 elderly volunteers drank fermented milk containing 4 x 1010 live cells of Lactobacillus casei strain Shirota daily for 3 wk, and their natural killer (NK) activity and other immunological functions were examined. In the experiments with middle-aged volunteers, NK activity significantly increased (P < 0.01) 3 wk after the start of intake, elevated NK cell activity remained for the next 3 wk, and this effect was particularly prominent in the low-NK-activity individuals. In the experiments with elderly volunteers, NK activity significantly decreased (P < 0.01) in the control group 3 wk after the start of intake; however, the intake of Lactobacillus casei strain Shirota maintained the NK activity. These results suggest that daily intake of Lactobacillus casei strain Shirota provides a positive effect on NK-cell activity.
BACKGROUND: Lactobacillus casei strain
Shirota L. casei Shirota (SHIROTA strain)
has been found to exert antiallergic effects in animal experiments, but
there is little information about its clinical effects in human patients
METHODS:We performed a randomized double-blind, placebo-controlled study to investigate the effects of L. casei Shirota (SHIROTA strain) in patients with allergic rhinitis triggered by Japanese cedar pollen (JCP). Participants were asked to drink fermented milk containing L. casei Shirota (SHIROTA strain) group or placebo (control group) for 8 weeks. Clinical symptoms and immunological parameters were compared between the two groups.
RESULTS:Symptom-medication scores (SMS) worsened in accordance with the increase in the amount of scattered JCP. In terms of the nasal and ocular SMS, there was no significant difference between the L. casei Shirota (SHIROTA strain) group and the placebo group during the ingestion period. In the subgroup of patients with moderate-to-severe nasal symptom scores before starting the ingestion of test samples, supplementation with L. casei Shirota (SHIROTA strain) tended to reduce nasal SMS.
CONCLUSION:These results indicate that fermented milk containing L. casei Shirota (SHIROTA strain) does not prevent allergic symptoms in patients sensitive to JCP, but may delay the occurrence of allergic symptoms in patients with moderate-to-severe nasal symptom scores.
We conducted a placebo-controlled, cross-over trial to examine the effect of L. casei Shirota (SHIROTA strain) L. casei Shirota (SHIROTA strain) on natural killer (NK) cell activity in humans. NK cell activity exhibited a declining trend during the period of placebo ingestion, but NK cell activity increased after intake for 3 weeks of fermented milk containing 4 x 1010live L. casei Shirota (SHIROTA strain) . When human peripheral blood mononuclear cells were cultured in the presence of heat-killed L. casei Shirota (SHIROTA strain) , NK cell activity was enhanced. The ability of L. casei Shirota (SHIROTA strain) to enhance NK cell activity and induce interleukin (IL)-12 production was correlated, and the addition of anti-IL-12 monoclonal antibody reduced the enhancement of NK cell activity triggered by L. casei Shirota (SHIROTA strain) . In addition, separation of NK cells from L. casei Shirota (SHIROTA strain) -stimulated monocytes with membrane filter reduced NK cell activity to the intermediate level and almost deprived monocytes of the ability to produce IL-12. These results demonstrate that L. casei Shirota (SHIROTA strain) can enhance NK cell activity in vivo and in vitro in humans, and IL-12 may be responsible for enhancement of NK cell activity triggered by L. casei Shirota (SHIROTA strain) .
BACKGROUND:Habitual smoking significantly reduces
natural killer (NK) cell activity. To clarify whether the intake of
fermented milk containing lactic acid bacteria restores NK cell activity
in habitual smokers, we conducted a placebo-controlled double-blind
RESULTS: NK cell activity in individuals was inversely correlated to numbers of cigarettes smoked. Averaged NK cell activity adjusted by the numbers of cigarettes was significantly higher in individuals drinking fermented milk containing L. casei than those drinking a placebo. However, the proportion of NK cells was not different between individuals drinking either fermented milk containing L. casei or the placebo.
CONCLUSIONS:Intake of fermented milk containing lactic acid bacteria was considered effective for restoring the NK cell activity of habitual smokers.
Nine healthy volunteers drank fermented milk containing 4 x 1010 live cells of Lactobacillus casei strain Shirota daily for 3 weeks, and their NK activity and other immunological functions were measured. NK activity significantly increased (p < 0.01) 3 weeks after the start of intake and remained elevated for the next 3 weeks. The effect was particularly prominent in low-NK-individuals.
Intestinal microbiota profiles of healthy pre-school and school-age children and effects of probiotic supplementation.Wang C et al 2015, Ann Nutr Metab 67:257-266.
1. Probiotic L. casei Shirota (SHIROTA strain) improves kidney function, inflammation and bowel movements in hospitalized patients with acute gastroenteritis – A prospective study.Akoglu B et al 2015, J Functional Foods 17:305-313.
Aim: The study was conducted in Germany to evaluate the role of the probiotic Lactobacillus casei Shirota (L. casei Shirota (SHIROTA strain) ) in improving kidney function, inflammation and bowel movement.
Method: 142 hospitalized patients with symptoms of acute gastroenteritis received 65 ml L. casei Shirota (SHIROTA strain) fermented milk twice daily.
Results: Intervention with L. casei Shirota (SHIROTA strain) resulted in a significant decrease in daily average (-5.42 vs. -4.40) and cumulative rate of bowel movements (-32.49 vs. -26.43) and improvement of the glomerular filtration rate (after 24 hours: 41.9 ± 2.8 vs. 25.9 ± 4.2 ml/min, p < 0.01). Furthermore, treatment with L. casei Shirota (SHIROTA strain) resulted in a significant decrease of CRP on days five, six and seven. Leukocyte counts decreased in all groups, however on day three the effect was significantly higher in the L. casei Shirota (SHIROTA strain) group receiving antibiotics. The administration of L. casei Shirota twice a day had positive effects on the reduction of bowel movements, improvement of kidney function and inflammation compared to the control group.
Conclusions: The study suggests that L. casei Shirota (SHIROTA strain) administration might be considered in those patients with acute gastroenteritis who present with high inflammation markers and / or acute impaired kidney function.
2. A L. casei Shirota (SHIROTA strain) probiotic drink reduces antibiotic-associated diarrhoea in patients with spinal cord injuries: a randomised controlled trial.Wong S et al (2013) British Journal of Nutrition 18:1-7.
Certain probiotics may prevent the development of antibiotic-associated diarrhoea (AAD) and Clostridium difficile-associated diarrhoea (CDAD), but their effectiveness depends on both strain and dose. There are few data on nutritional interventions to control AAD/CDAD in the spinal cord injury (SCI) population. The present study aimed to assess (1) the efficacy of consuming a commercially produced probiotic containing at least 6•5 billion live L. casei Shirota (SHIROTA strain) (L. casei Shirota (SHIROTA strain) ) in reducing the incidence of AAD/CDAD, and (2) whether undernutrition and proton pump inhibitors (PPI) are risk factors for AAD/CDAD. A total of 164 SCI patients (50•1 (SD 17•8) years) with a requirement for antibiotics (median 21 d, range 5–366) were randomly allocated to receive L. casei Shirota (SHIROTA strain) (n 76) or no probiotic (n 82). L. casei Shirota (SHIROTA strain) was given once daily for the duration of the antibiotic course and continued for 7 days thereafter. Nutritional risk was assessed by the Spinal Nutrition Screening Tool. The L. casei Shirota (SHIROTA strain) group had a significantly lower incidence of AAD (17•1 v. 54•9%, P 0•001). At baseline, 65% of patients were at undernutrition risk. Undernutrition (64•1 v. 33•3%, P0•01) and the use of PPI (38•4 v. 12•1%, P¼0•022) were found to be associated with AAD. However, no significant difference was observed in nutrient intake between the groups. The multivariate logistic regression analysis identified poor appetite (1/2 meals eaten) (OR 5•04, 95% CI 1•28, 19•84) and no probiotic (OR 8•46, 95% CI 3•22, 22•20) as the independent risk factors for AAD. The present study indicated that L. casei Shirota (SHIROTA strain) could reduce the incidence of AAD in hospitalized SCI patients. A randomised, placebo-controlled study is needed to confirm this apparent therapeutic success in order to translate into improved clinical outcomes.
1. Differential Effects of Lactobacillus casei Strain Shirota on Patients with Constipation Regarding Stool Consistency in China.Chen S et al. 2019. J Neurogastroenterol Motil. .25(1):148-158
This study conducted in China investigated the effect of Lactobacillus casei strain Shirota (L. casei Shirota (SHIROTA strain) ) on constipation-related symptoms, especially stool consistency, of constipated patients who met the Rome III criteria. They were divided into 3 groups according to the Bristol Stool Form Scale – hard, normal and soft stools. Subjects in each group consumed a probiotic beverage containing 10¹⁰ CFU of L. casei Shirota (SHIROTA strain) daily for 28 days. L. casei Shirota (SHIROTA strain) intervention significantly alleviated constipation-related symptoms and increased defecation frequency in all subjects. Four weeks of L. casei Shirota (SHIROTA strain) supplementation softened the hard stools, hardened the soft stools, and did not alter the ideal stool consistency in the normal stools. The short-chain fatty acid (SCFA) concentrations were highest in Soft stool , followed by normal stool and hard stool. L. casei Shirota (SHIROTA strain) intervention increased the stool SCFA levels in hard stool but reduced or did not alter the levels in normal and soft stools. LcS intervention increased the Pseudobutyrivibrio and Roseburia abundance in hard stool and decreased the Pseudobutyrivibrio abundance in soft stool. The study concluded that L. casei Shirota (SHIROTA strain) supplementation improved the constipation-related symptoms in constipated subjects and balanced the stool consistency-softened the hard stools and hardened the Soft stools.
2. Use of probiotics for the treatment of constipation in Parkinson's disease patients.Cassani E et al (2011) Minerva Gastroenterol Dietol.;57(2):117-21.
AIM: To assess the effects of milk fermented with the probiotic strain L. casei Shirota (SHIROTA strain) on constipation in Parkinson's disease (PD) patients. The effects of the administration of L. casei Shirota (SHIROTA strain) on gastrointestinal symptoms have been assessed in two randomized controlled trials on patients suffering from chronic constipation.
METHODS: 40 Parkinson’s disease (PD) patients suffering from constipation according (Rome III) criteria were recruited. We compared the characteristic of intestinal function during two periods with different treatments: in the first week, the patients treated constipation only with dietetic therapy; in the following 5 weeks, the patients treated constipation not only with dietetic therapy, but also taking a 65mL fermented milk drink containing 6.5×109 CFU of L. casei Shirota (SHIROTA strain) daily. They completed a daily diary for 6 weeks, recording details related to their intestinal function.
RESULTS: After probiotic intake, observed a statistically significant increase in the number of days per week in which stools were of normal consistency (P<0.01) and significant reductions in the number of days per week in which patients felt bloated (P<0.01), experienced abdominal pain (P<0.01) and sensation of incomplete emptying (P<0.01).
CONCLUSIONS: This pilot study showed that a regular intake of probiotics can significantly improve stool consistency and bowel habits in Parkinson's disease patients
3. Effects of a probiotic fermented milk on functional constipation: a randomized, double-blind, placebo-controlled study.Mazlyn MM, Nagarajah LH, Fatimah A, Norimah AK, Goh KL (2013) J Gastroenterol Hepatol 28(7):1141-7.
BACKGROUND AND AIM: Evidence suggests that probiotics reduce certain constipation-related symptoms. Lactobacillus casei strain Shirota has never been tested as treatment for functional constipation in otherwise-healthy subjects. To evaluate the efficacy of this probiotic among adults with functional constipation was aimed.
METHODS: Subjects with functional constipation (Rome II-defined) were randomized to intake L. casei strain Shirota fermented milk or placebo once daily for 4 weeks under double-blind condition. Primary outcomes were constipation severity and stool frequency; secondary outcomes were stool consistency and quantity.
RESULTS: In intent-to-treat population, compared with baseline, constipation severity and stool frequency improved in both probiotic (n=47) and control groups (n=43), but improvements were comparable in both groups at week 4 (a=5% level). In probiotic group, stool consistency and quantity at week 4 improved significantly versus baseline but not versus control. Considering that the study agent is non-pharmaceutical and the purpose of supplementation is for long-term effect, re-evaluation at a=10% was conducted, which showed significant improvement in constipation severity at week 4 (P=0.058). Magnitude of the probiotic effect on stool consistency was small but grew over time, d=0.19, 95% confidence interval 0.00-0.35 (Week 4), d=0.29, 95% confidence interval 0.11-0.52 (post intervention). Post-hoc exploratory analysis suggests incomplete evacuation may decrease with probiotic intake.
CONCLUSIONS: Four-week administration of L. casei strain Shirota did not alleviate constipation severity or stool frequency, consistency, and quantity when compared with control. With re-evaluation at a=10% level, improvement in constipation severity was significant at week 4. To obtain conclusive results, further studies with longer intervention are warranted.
4. Effect of L. casei Shirota (SHIROTA strain) on colonic transit time in patients with chronic constipation.Krammer HJ et al (2011) Coloproctology 33: 109-113.
Background Slow-transit constipation (STC) is caused by a motility disorder of the colon which leads to delayed transit (>72 h). The probiotic strain Lactobacillus casei Shirota L. casei Shirota (SHIROTA strain) has been shown to improve constipation-related symptoms, such as stool frequency and consistency. A randomized double-blind placebo-controlled trial was performed to determine the effect of (L. casei Shirota (SHIROTA strain) ) on the colonic transit time in patients with STC.
Patients and methods Colonic transit time of all consecutive outpatients with chronic constipation was determined by the Hinton test using radiopaque markers. Patients with a transit time longer than 72 h were included in the study. A total of 24 patients received either a dairy drink containing 6.5×109 colony forming units (cfu) of (L. casei Shirota (SHIROTA strain) ) or a placebo daily for 4 weeks. General gastrointestinal symptoms were evaluated weekly by a questionnaire and the measurement of colonic transit time was repeated after the intervention.
Results The intake of (L. casei Shirota (SHIROTA strain) ) resulted in a significant acceleration of the total colonic transit time from 95.6 h to 76.5 h (p=0.05). This effect was most pronounced in the sigmoid and rectum transit time (p< 0.007). In the placebo group no statistically significant change in the total colonic transit time was observed (before: 95.8 h, after: 87.1 h, p=0.282)
Conclusion The daily intake of a probiotic drink containing (L. casei Shirota (SHIROTA strain) ) significantly reduced the colonic transit time in patients with STC.
5. A Probiotic Fermented Milk Drink containing Lactobacillus casei stain Shirota improves stool consistency of subjects with hard stools.Tilley L, Keppens K, Kushiro A, Takada T, Sakai T, Vaneechoutte M and Degeest B (2014). International Journal of Probiotics and Prebiotics. 9 (1/2) 23-30.
The aim of this study was to investigate the effect of a fermented milk drink containing Lactobacillus casei strain Shirota L. casei Shirota (SHIROTA strain) on the bowel habit of subjects suffering from hard stools. It was also trsted whether the probiotic strain was able to survive through the gastrointestinal tract. A double blind placebo controlled randomized study was carried out over an eight week period in subjects with symptoms of constipation (n=120). All subjects received 65 ml / day of probiotic fermented milk drink containing L. casei Shirota (SHIROTA strain) or placebo. Patients completed a questionnaire to assess the consistency of their stools. The survival of the probiotic strain L. casei Shirota (SHIROTA strain) was tested using culture and an L. casei Shirota (SHIROTA strain) specific monoclonal antibody for identification of the colonies as L. casei Shirota (SHIROTA strain) (ELISA). There was a significant decrease in stool hardening when the fermented milk drink was consumed. The observed clinical effect was underpinned by the microbiological effect as the number of viable L. casei Shirota (SHIROTA strain) bacteria in the faeces increased when consuming the fermented milk drink and decreased during the wash out.
6. Fermented milk containing Lactobacillus casei strain Shirota reduces incidence of hard or lumpy stools in healthy population.Sakai T et al (2011) International Journal of Food Sciences and Nutrition 62(4): 423-430.
The objective of the present study was to investigate the efficacy of fermented milk containing Lactobacillus casei strain Shirota L. casei Shirota (SHIROTA strain) in a healthy population. Healthy subjects with Bristol Stool Form Scale (BS) score < 3.0 were randomized to fermented milk treatment for 3 weeks or non-intervention control. The primary endpoint was the proportion of subjects that produced hard or lumpy stools (HLS) = 25% of bowel movements (H-HLS). Secondary endpoints included changes in BS score, constipation-related symptom scores and stool parameters. Efficacy was analyzed in 39 subjects. After 3 weeks of treatment the proportion of H-HLS subjects had significantly decreased from 73.7% to 36.8%, whereas in the control group the proportion had increased from 75.0% to 85.0% during the same period (P = 0.002). The BS score was significantly improved after the treatment compared with the control (P < 0.001). In conclusion, daily consumption of fermented milk containing L. casei Shirota (SHIROTA strain) reduced the incidence of HLS.
7. Effects of a probiotic fermented milk beverage containing Lactobacillus casei strain Shirotaon defecation frequency, intestinal microbiota and the intestinal environment of healthy individuals with soft stools.Matsumoto K, Takada T, Shimizu K, Moriyama K, Kawakami K, Hirano K, Kajimoto O, Nomoto K (2010) Journal of Bioscience & Bioengineering doi: 10.1016/j.jbiosc.2010.05.016.
The effects of drinking a fermented milk beverage that contains Lactobacillus casei strain Shirota L. casei Shirota (SHIROTA strain) at 40 billion bacterial cells/bottle for 4 weeks (probiotics, 1 bottle/day) on defecation frequency, intestinal microbiota and the intestinal environment of healthy individuals with soft stools were evaluated. Thirty-four healthy adults who had soft stools were randomised into 2 groups, and the effects of a regular 4-week intake of probiotics were evaluated by a placebo-controlled, double-blind, parallel-group comparative design. Defecation frequency significantly decreased after the 4-week intake period compared with before the probiotic treatment. The stool quality significantly improved (hardened) compared to the placebo. Also, the water content of the stools was lower in the probiotic group than in the placebo group. Live L. casei Shirota (SHIROTA strain) was recovered at 6.9 ± 1.3 and 7.2 ± 0.8 log (10) CFU per 1g of stool after 2 and 4 weeks, respectively, of probiotic treatment. The number of bifidobacteria in the stools also increased significantly compared with the level before starting the probiotics. The organic acid levels (total, acetic acid, propionic acid, and butyric acid) significantly increased compared with the level before intake in both the probiotic and placebo groups, but they returned to the original levels after the end of the intake period. These results suggest that probiotic fermented milk beverage has an intestine-conditioning effect by improving the frequency of defecation and stool quality and increasing the intrinsic bifidobacteria in healthy individuals with soft stool.
8. The effect of a probiotic milk product containing Lactobacillus casei strain Shirota on the defecation frequency and the intestinal microflora of sub-optimal health state volunteers: a randomized placebo-controlled cross-over study.Matsumoto K, Takada T, Shimizu K, Kado Y, Kawakami K et al (2006) Bioscience and Microflora 25(2): 39-48.
Objective To assess the effect of a probiotic on
bowel habit, intestinal microflora and other parameters of
intestinal health in healthy subjects with low defecation
Methods In a double-blind, placebo-controlled, randomized crossover trial, one bottle a day of probiotic (minimum 4 x 1010 cfu L. casei Shirota) or placebo was given to 40 healthy people selected on the basis of low defecation frequency (3-5 times/week). Subjects were randomly allocated to different intervention sequences, with each intervention lasting two weeks and separated by a three-week washout period. They kept a daily record of their defecation frequency and stool appearance. Microbiological and biochemical analysis of the faeces were conducted at six different time points.
Results The main changes observed for the measured endpoints included an increase in defecation frequency for the probiotic intervention period (P < 0.05). This was most noticeable in those who had initially had the lowest defecation frequency (= 4.0 per week; n=21). Significant improvement in the stool smell and the feeling of completeness in emptying the bowels was also reported during the probiotic consumption (both P < 0.05). In addition, stool consistency changed to become softer for subjects with a stronger tendency to constipation (P < 0.05).
An increase of Bifidobacteria numbers and their percentage of total number of faecal bacteria was observed associated with probiotic intervention compared to before probiotic intake and also compared to placebo intake at week two (both P < 0.05)
Selective culture methods demonstrated counts of = Log10 7.3 /per g of faeces for the probiotic strain (L. casei Shirota) during both weeks of probiotic intervention.
No differences in other parameters of faecal analysis were found (i.e. other bacterial groups, organic acids, putrefactive metabolites, pH and water content).
Table 1. Changes in bowel movements (frequency per week) for constipated subjects " ">
Week 1 of intake
Week 2 of intake
All subjects (n=40)
4.0 ± 1.3
4.7 ± 1.5 *
4.8 ± 1.5*
4.2 ± 1.5
4.4 ± 1.7
4.3 ± 1.5
Those with more severe constipation (n=21)
3.2 ± 1.0
4.2 ± 1.5 *
4.7 ± 1.7**
3.3 ± 1.3
3.8 ± 1.4
3.7 ± 1.3
Comparison with values before intake: * P < 0.05; ** P < 0.01 (Wilcoxon signed-rank test); Comparison between probiotic and placebo: ¶ P < 0.05 (Wilcoxon signed-rank test)
Conclusions The authors concluded that the results indicated that the probiotic positively influenced the gut by improving bowel habit and stool quality, and increasing levels of bifidobacteria.
9. The effects of a synbiotic fermented milk beverage containing Lactobacillus casei strain Shirota and transgalactosylated oligosaccharides on defecation frequency, intestinal microflora, organic acid concentrations, and putrefactive metabolites of sub-optimal health state volunteers: a randomized placebo-controlled cross-over study.Shioiri T, Yahagi K, Nakayama, S, Asahara T, Yuki N, Kawakami K, Yamaoka Y, Sakai Y, Nomoto K, Totani M (2006) Bioscience and Microflora 25(4):137-146.
Methods :Subjects were selected for the study on the basis of a prior screen, which identified female students who were constipated and elderly people with apparently abnormal gut microflora and levels of putrefactive intestinal metabolites. In a double-blind, placebo-controlled, crossover trial, 35 female university students and 20 healthy elderly people were given one bottle (80 ml) a day of the synbiotic or a placebo. The subjects were allocated randomly to a treatment sequence (synbiotic-placebo or placebo-synbiotic), with each intervention period lasting two weeks and separated by a washout period of three weeks. Evaluation of benefit was by measurement of defecation frequency, number of days with bowel movements, stool quantity, and assessment of changes in the intestinal milieu by microbiological and biochemical analysis of faeces.
Results :For the constipated students, after one week of synbiotic intervention, their defecation frequency increased significantly compared to the baseline frequency (P < 0.01), and also in comparison to the placebo intervention (P < 0.05)
Faecal analysis of the elderly subjects showed an increase in Bifidobacteria and Lactobacilli associated with the synbiotic intervention (P < 0.05 and P < 0.01 respectively). This was significantly higher than baseline levels, as well as in comparison to the placebo intervention. Compared to the placebo intervention, there was also a significant decrease of lecithinase-positive clostridia counts after one week of synbiotic intervention (P < 0.05), as well as a significant decrease of Enterobacteriaceae after 1 and 2 weeks synbiotic intervention (P < 0.01). The probiotic strain L. casei Shirota was recovered during the intervention period at 107 CFU per gram of faeces.
Compared to the placebo intervention, faecal levels of acetic acid were significantly higher in the synbiotic group (P < 0.01). After one and two weeks of synbiotic intervention, there was a significant decrease in faecal pH, as well as levels of ammonia and phenol (P < 0.05 respectively).
Table. Changes in bowel movements (frequency per week) with synbiotic (constipated students)
Week 1 of intake
Week 2 of intake
All subjects (n=40)
4.0 ± 1.3
4.7 ± 1.5 *
4.8 ± 1.5*
4.2 ± 1.5
4.4 ± 1.7
4.3 ± 1.5
Those with more severe constipation (n=21)
3.2 ± 1.0
4.2 ± 1.5 *
4.7 ± 1.7**
3.3 ± 1.3
3.8 ± 1.4
3.7 ± 1.3
Conclusions The authors concluded that the results indicated that the probiotic positively influenced the gut by improving bowel habit and stool quality, and increasing levels of bifidobacteria.
1. Probiotic effects on intestinal fermentation patterns in patients with irritable bowel syndrome.Barrett JS, Canale KEK, Gearry RB, Irving PM, Gibson PR (2008) World Journal of Gastroenterology 14(32): 5020-5024.
METHODS: 18 patients with IBS (Rome II criteria), who showed an early rise in breath hydrogen with lactulose (ERBHAL), consumed 65 mL of Yakult daily for 6 wk. Lactulose breath test was repeated at the end of the treatment period. Symptoms were recorded daily using a 10 cm visual analogue scale.
RESULTS:14 patients completed the study, 9 (64%) had reversal of ERBHAL, with the median time of first rise in breath hydrogen increasing from 45 to 75 min (P = 0.03). There was no significant improvement in the symptom score with probiotic therapy, except for wind (P = 0.04). Patients commencing with at least moderate symptoms and who no longer had ERBHAL at the end of treatment, showed improvement in the overall symptoms scores [median final score 5.3 (IQR 3.9-5.9), 55% reduction; n = 6] to a greater extent than those who had had persisting ERBHAL [final score 6.9 (5.0-7.0), 12% reduction; n = 5; P = 0.18].
CONCLUSION: Yakult is effective in altering fermentation patterns in the small bowel, consistent with reducing SIBO. The loss of ERBHAL was associated with reduced symptoms. The true interpretation of these findings awaits a randomised, controlled trial.
1. Dysregulated Circulating Dendritic Cell Function in Ulcerative Colitis Is Partially Restored by Probiotic Strain Lactobacillus casei Shirota.Mann ER, You J, Horneffer-van der Sluis V, Bernardo D et al (2013) Mediators Inflamm 573576. doi: 10.1155/2013/573576.
Methods : Human blood DC from healthy controls (control-DC) and UC patients (UC-DC) were conditioned with heat-killed L. casei Shirota (SHIROTA strain) and used to stimulate allogeneic T cells in a 5-day mixed leucocyte reaction.
Results : UC-DC displayed a reduced stimulatory capacity for T cells (P < 0.05) and enhanced expression of skin-homing markers CLA and CCR4 on stimulated T cells (P < 0.05) that were negative for gut-homing marker ß7. L. casei Shirota (SHIROTA strain) treatment restored the stimulatory capacity of UC-DC, reflecting that of control-DC. L. casei Shirota (SHIROTA strain) treatment conditioned control-DC to induce CLA on T cells in conjunction with ß7, generating a multihoming profile, but had no effects on UC-DC. Finally, L. casei Shirota (SHIROTA strain) treatment enhanced DC ability to induce TGFß production by T cells in controls but not UC patients.
Conclusions : We demonstrate a systemic, dysregulated DC function in UC that may account for the propensity of UC patients to develop cutaneous manifestations. L. casei Shirota (SHIROTA strain) has multifunctional immunoregulatory activities depending on the inflammatory state; therapeutic effects reported in UC may be due to promotion of homeostasis
2. Beneficial effects of Lactobacillus casei in ulcerative colitis: a pilot study.Mitsuyama K, Matsumoto S, Yamasaki H, Masuda J, Kuwaki K et al (2008) Journal of Clinical Biochemistry & Nutrition 43 (Suppl 1): 78-81 (2008).
The control group consisted of nine previously treated patients with active UC whose baseline characteristics were similar to the study group and had previously received conventional therapy but not a probiotic.
In addition, the effect of heat-treated L. casei Shirota (SHIROTA strain) on IL-6 production was assessed in vitro in samples of lipopolysaccharide stimulated peripheral blood mononuclear cells (PBMC) from patients with active UC.
Results :Compared to the control group, probiotic consumption was associated with significantly improved clinical activity index scores after four weeks (P = 0.033), six weeks (P = 0.026) and eight weeks (P = 0.012). When compared to pre-treatment clinical activity index scores, a trend for improved clinical status was observed in the probiotic group but not in the control group at six weeks (P = 0.010) and eight weeks (P = 0.035). The probiotic was well tolerated and no adverse effects were reported.
In vitro tests showed that L. casei Shirota (SHIROTA strain) inhibited IL-6 production in PBMC of UC patients.
Conclusions :The data indicate that supplementing conventional UC therapy with L. casei Shirota (SHIROTA strain) is safe and more effective in achieving clinical improvement of active UC compared to conventional treatment alone.
The probiotic mechanism of activity may involve inhibition of IL-6 signalling since this cytokine is thought to promote intestinal inflammation.
These findings need to be confirmed in a larger, randomised controlled trial.
3. Anti-inflammatory effects of probiotic Lactobacillus casei strain Shirota in chronic intestinal inflammatory disorders.Matsumoto S (2008) International Journal of Probiotics and Prebiotics 3(3): 149-152.
4. High dose probiotic and prebiotic co-therapy for remission induction of active Crohn's disease.Fujimori S, Tatsuguchi A, Gudis K, Kishida T, Mitsui K et al (2007) Journal of Gastroenterology & Hepatology22: 1199-204.
METHOD: Ten active CD outpatients without history of operation for CD were enrolled. Their mean (+/-SD) age was 27 +/- 7 years and the main symptoms presented were diarrhea and abdominal pain. Patients' initial therapeutic regimen of aminosalicylates and prednisolone failed to achieve remission. Patients were thus initiated on a synbiotic therapy, consisting of both probiotics (75 billion colony forming units [CFU] daily) and prebiotics (psyllium 9.9 g daily). Probiotics mainly comprised Bifidobacterium and Lactobacillus. Patients were free to adjust their intake of probiotics or prebiotics throughout the trial. Crohn's disease activity index (CDAI), International Organization for the Study of Inflammatory Bowel Disease (IOIBD) score and blood sample variables were evaluated and compared before and after the trial.
RESULTS:The duration of the trial was 13.0 +/- 4.5 months. By the end of therapy, each patient had taken a 45 +/- 24 billion CFU daily probiotic dose, with six patients taking an additional 7.9 +/- 3.6 g daily psyllium dose. Seven patients had improved clinical symptoms following combined probiotic and prebiotic therapy. Both CDAI and IOIBD scores were significantly reduced after therapy (255-136, P = 0.009; 3.5-2.1, P = 0.03, respectively). Six patients had a complete response, one had a partial response, and three were non-responders. Two patients were able to discontinue their prednisolone therapy, while four patients decreased their intake. There were no adverse events.
CONCLUSION: High-dose probiotic and prebiotic cotherapy can be safely and effectively used for the treatment of active CD.
5. Probiotic effects of Lactobacillus casei on DSS-induced ulcerative colitis in mice.Herias MV, Koninkx JFJG, Vos JG, HuisIn't Veld JHJ, van Dijk JE (2005) International Journal of Food Microbiology 2: 143-155 .
6. A component of polysaccharide peptidoglycan complex on Lactobacillus induced an improvement of murine model of inflammatory bowel disease and colitis-associated cancer.Matsumoto S, Hara T, Nagaoka M, Mike A, Mitsuyama K, Sako T et al (2008) Immunology 128: e170-e180.
1. Effect of administration of Lactobacillus casei strain Shirota on sodium balance in an infant with short bowel syndrome.Candy, DCA et al (2001) Journal of Pediatric Gastroenterology and Nutrition 32(4), 506 -508 .
2. Combination therapy with Bifidobacteriumbreve, Lactobacillus casei strain Shirota and galactooligosaccharides dramatically improve the intestinal function in a girl with short bowel syndrome : a novel synbiotic therapy for intestinal failure.Kanamori Y etal (2001) Digestive diseases and Science 46 (9), 2010 - 2016.
3. Experience of long term symbiotic therapy in seven short bowel patients with refractory enterocolitis.Kanamori Y et al (2004) Journal of Pediatric surgery 39 (11), 1686 -1692.
4. Immunonutritional effects during symbiotic therapy in pediatric patients with short bowel syndrome.Uchida K et al (2007) Pediatric Surgery International 23, 243 - 248.
1. In vitro and in vivo inhibition of Helicobacter pylori by Lactobacillus casei strain Shirota.Sgouras D, Maragkoudakis P, Petraki K, Martinez-Gonzalez B, Eriotou E, Michopoulos S, Kalantzopoulos G, Tsakalidou E, Mentis A (2004) Applied and Environmental Microbiology 70(1): 518-26 .
2. Effect of frequent consumption of a Lactobacillus casei -containing milk drink in Helicobacter pylori- colonized subjects.Cats A, Kuipers EJ, Bosscharts MAR, Pot RGJ, Vandenbroucke-Grauls CMJE, Kusters JG (2003) Alimentary Pharmacology and Therapeutics 17(3): 429-435.
AIM:To test whether a drink containing Lactobacillus casei strain Shirota inhibits Helicobacter pylori growth.
METHODS:The in vitro growth inhibition of H. pylori was studied when L. casei was added to plates previously inoculated with H. pylori reference strain NCTC 11637. In an intervention study, 14 H. pylori-positive subjects were given Yakult drink (10(8) colony-forming units/mL L. casei) thrice daily during meals for 3 weeks. Six untreated H. pylori-positive subjects served as controls. H. pylori bacterial loads were determined using the 13C-urea breath test, which was performed before and 3 weeks after the start of L. casei supplementation.
RESULTS: In vitro, L. casei inhibits H. pylori growth. This effect was stronger with L. casei grown in milk solution than in DeMan-Rogosa-Sharpe medium. No growth inhibition was shown with medium inoculated with lactic acid, Escherichia coli strain DH5alpha or uninoculated medium. Filtration of L. casei culture before incubation with H. pylori completely abolished the inhibitory effect. Urease activity decreased in nine of the 14 (64%) subjects with L. casei supplementation and in two of the six (33%) controls (P = 0.22).
CONCLUSIONS:Viable L. casei are required for H. pylori growth inhibition. This does not result from changes in lactic acid concentration. In addition, a slight, but non-significant, trend towards a suppressive effect of L. casei on H. pylori in vivo may exist.
1. L. casei Shirota (SHIROTA strain) protects from fructose-induced liver steatosis: a mouse model.CWagnerberger S, Spruss A, Kanuri G, Stahl C et al (2013) J Nutr Biochem 24(3):531-8.
2. Anticarcinogenic effect of probiotic fermented milk and chlorophyllin on aflatoxin-B1-induced liver carcinogenesis in rats.Kumar M et al (2012) British Journal of Nutrition 107(7):1006-16.
3. Perioperative synbiotic treatment to prevent infectious complications in patients after elective living donor liver transplantation. A prospective randomized study.Eguchi S, Tatatsuki M, Hidaka M, Soyama A, Ichikawa T, Kanematsu T (2010) The American Journal of Surgery doi: 10.1016/j.amjsurg.2010.02.013.
METHODS:Fifty adult patients undergoing LDLT between September 2005 and June 2009 were randomized into a group receiving 2 days of preoperative and 2 weeks of postoperative synbiotic therapy (Bifidobacterium breve, Lactobacillus casei , and galactooligosaccharides [the BLO group]) and a group without synbiotic therapy (the control group). Postoperative infectious complications were recorded as well as fecal microflora before and after LDLT in each group.
RESULTS:Only 1 systemic infection occurred in the BLO group (4%), whereas the control group showed 6 infectious complications (24%), with 3 cases of sepsis and 3 urinary tract infections with Enterococcus spp (P = .033 vs BLO group). No other type of complication showed any difference between the groups.
CONCLUSIONS:Infectious complications after elective LDLT significantly decreased with the perioperative administration of synbiotic therapy.
4. Effect of probiotic treatment on deranged neutrophil function and cytokine responses in patients with compensated alcoholic cirrhosis.Stadlbauer, V, Mookerjee, RP, Hodges, SJ, Wright, G, Davies, NA, Jalan, R (2008) Journal of Hepatology 48(6): 945-951.
METHODS:In an open-label study, patients with alcoholic cirrhosis (n=12) received L. casei Shirota (SHIROTA strain) (6.5 x 10(9)) 3 times daily for 4 weeks. Data were compared to healthy controls (n=13) and cirrhotic patients (n=8) who did not receive probiotics. Neutrophil oxidative burst, phagocytosis, toll-like-receptor (TLR) expression, plasma cytokines and ex vivo endotoxin-stimulated cytokine production were measured.
5. Anticarcinogenic effect of probiotic fermented milk and chlorophyllin on aflatoxin-B1-induced liver carcinogenesis in rats.Kumar M et al (2012) British Journal of Nutrition 107(7):1006-16.
6. Lactobaccilus casei Shirota protects from fructose-induced liver steatosis: A mouse model..Wagnerberger S et al (2012) J Nutr Biochem Jun 27.
1. Probiotic Beverage with Soy Isoflavone Consumption for Breast Cancer Prevention: A Case-control Study.Toi M, Hirota S, Tomotaki A, Sato N, Hozumi Y, Anan K, Nagashima T et al (2013) Curr Nutr Food Sci 9(3):194-200.
1. Probiotics enhance the clearance of human papillomavirus-related cervical lesions: a prospective controlled pilot study.Verhoeven V, Renard N, Makar A, Royen PV, Bogers JP, Lardon F et al (2012) Eur J Cancer Prev 22(1):46-51.
1. Randomized trial of dietary fiber and Lactobacillus casei administration for prevention of colorectal tumours.Ishikawa H, Akedo I, Otani T, Suzuki T, Nakamura T et al (2005) International Journal of Cancer 116: 762-767.
2. The enhancing effect of oral Lactobacillus casei on the immunologic activity of colon cancer patients.Sawamura A, Yamaguchi Y, Toge T, Nagata N, Ikeda H et al (1994) Biotherapy 8(12): 1567-1572.
The above findings show that oral BLP has an activating effect on host-mediated immunity in patients at early stages of colon cancer.
3. The effect of an oral administration of Lactobacillus casei strain Shirota on azoxymethane-induced colonic aberrant crypt foci and colon cancer in the rat.Yamazaki K, Tsunoda A, Shibusawa M, Tsunoda Y, Kusano M et al (2000) Oncology Report 7(5): 977-982.
1. Lactobacillus casei strain Shirota and prevention of recurrence of bladder cancer.Naito S (2008) International Journal of Probiotics and Prebiotics 3(3): 163-164.
2. Prevention of recurrence with Epirubicin and Lactobacillus casei after transurethral resection of bladder cancer.Naito S, Koga H, Yamaguchi A, Fujimoto N, Hasui Y et al (2008) Journal of Urology 179: 485-490.
Materials and Methods: Between August 1999 and December 2002, 207 patients clinically diagnosed with superficial bladder cancer were included as study candidates and underwent transurethral resection, followed by intravesical instillation of 30 mg epirubicin/30 ml saline twice during 1 week. After histological confirmation of superficial bladder cancer they were again included as study participants with 102 randomized to receive treatment with 6 additional intravesical instillations of epirubicin during the 3-month period after transurethral resection (epirubicin group) and 100 randomized to intravesical chemotherapy on the same schedule as the epirubicin group plus oral administration of 3 gm Lactobacillus casei preparation per day for 1 year (epirubicin plus Lactobacillus casei group). Patients were evaluated for intravesical recurrence, disease progression, prognosis and adverse drug reactions.
Results: The 3-year recurrence-free survival rate was significantly higher in the epirubicin plus Lactobacillus casei group than in the epirubicin group (74.6% vs 59.9%, p _ 0.0234), although neither progression-free nor overall survival differed between the groups. The incidence of adverse drug reactions did not significantly differ between the groups and there were no serious adverse drug reactions.
Conclusions: Intravesical instillation of epirubicin plus oral administration of Lactobacillus casei preparation is a novel, promising treatment for preventing recurrence after transurethral resection for superficial bladder cancer.
3. Habitual intake of lactic acid bacteria and risk reduction of bladder cancer.Ohashi Y, Nakai S, Tsukamoto T, Masumori N, Akaza H et al (2002) Urologia Internationalis 68: 273-280
Methods: A total of 180 cases (mean age: 67 years, SD 10) were selected from 7 hospitals, and 445 population-based controls matched by gender and age were also selected. Interviewers asked them 81 items. The conditional logistic regression was used to estimate adjusted odds ratios (OR).
Results: The OR of smoking was 1.61 (95% confidence interval: 1.10-2.36). Those of previous (10-15 years ago) intake of fermented milk products were 0.46 (0.27-0.79) for 1-2 times/week and 0.61 (0.38-0.99) for 3-4 or more times/week, respectively.
Conclusion: It was strongly suggested that the habitual intake of lactic acid bacteria reduces the risk of bladder cancer.
4. Antitumor effects of the intravesical instillation of heat killed cells of the Lactobacillus casei strain Shirota on the murine orthotopic bladder tumor MBT-2.Takahashi T, Kushiro A, Nomoto K, Uchida K, Morotomi M et al (2001) Journal of Urology 166: 2506-2511
5. Preventive effect of a Lactobacillus casei preparation on the recurrence of superficial bladder cancer in a double blind trial.Aso Y, Akaza H, Kotake T, Tsukamoto T, Imai K et al (1995) European Urology 27: 104-109.
6. Prophylactic effect of a Lactobacillus casei preparation on the recurrence of superficial bladder cancer.Aso Y, Akaza H (1992) Urology International 40: 125-129
1. Synbiotics reduce postoperative infectious complications: a randomized controlled trial in biliary cancer patients undergoing hepatectomy.Kanazawa H, Nagino M, Kamiya S, Komatsu S, Mayumi T et al (2005) Langenbeck's archives of surgery 390(2): 104-113.
Methods: Fifty-four patients with biliary cancer were randomly allocated to two groups before hepatectomy. One group received postoperative enteral feeding that included synbiotics; the other received enteral feeding only. Lactulose/mannitol (L/M) ratio, serum diamine oxidase (DAO) activity, and fecal microflora and organic acid concentrations were determined. Postoperative infectious complications were recorded.
Results: Of the 54 patients, 44 completed the trial (21 receiving synbiotics and 23 others as controls). Postoperative changes in L/M ratios and serum DAO activities were identical between the two groups. Numbers of beneficial bacteria increased in the synbiotics group after surgery but decreased in controls. Numbers of harmful microorganisms decreased in the synbiotics group but increased in controls. Total organic acid concentrations increased in the synbiotics group but decreased in controls. Incidence of infectious complications was 19% (4/21) in the synbiotics group and 52% (12/23) in controls (P < 0 .05 ). All study patients tolerated surgery (mortality 0%).
Conclusions: Synbiotics, combined with early enteral nutrition, can reduce postoperative infections. This beneficial effect presumably involves correction of an intestinal microbial imbalance induced by surgical stress.
1. Control of the carcinomatous pleural effusion with LC9018 and quality of life in lung cancer patients.Masuno T, Kishimoto S, Ogura T, Honma T, Niitani H et al (1994) Biotherapy 8(6): 847-856.
2. A comparative trial of LC9018 plus doxoburubicin and doxorubicin alone for the treatment of malignant pleural effusion secondary to lung cancer.Masuno T, Kishimoto S, Ogura T, Honma T, Niitani H et al (1991) Cancer 68(7): 1495-1500.
2. A comparative trial of LC9018 plus doxoburubicin and doxorubicin alone for the treatment of malignant pleural effusion secondary to lung cancer.Shida K and Nomoto K (2013) Indian J Med Res 138:808-814.
Aim: To demonstrate the gastrointestinal survival of Lactobacillus casei strain Shirota (LcS) in healthy Vietnamese adults.
Methods: Twenty-six healthy Vietnamese adults took part in the study. Each participant consumed 65 mL of a fermented milk drink containing LcS daily for 14 days. The drink contained a dose of 10 8 CFU/mL LcS . Fecal samples were collected before, during and after consuming the fermented milk drink.
Results: LcS was confirmed by culture and ELISA. After 7 and 14 days of ingesting fermented milk drink, LcS was recovered from fecal samples at average of 5.0×10 7 CFU/g feces (n=26) and 5.4×10 7 CFU/g feces (n=26), respectively. LcS persisted in 8 volunteers until day 42 (after 14 days stopping fermented milk drink) at 0.0033×10 7 CFU/g feces (n=8).
Conclusions: Confirmed the survival of LcS after passage through the gastrointestinal tract of Vietnamese adults.
Material and Method: First fecal samples were collected from 20 healthy adults at 10 days after they abstained from all lactobacillus containing milk products. Second specimens taken after the subjects ingested L. casei Shirota (SHIROTA strain) containing milk product for 7 days and third specimens at 7 days after they stopped taking L. casei Shirota (SHIROTA strain) containing milk product. All the fecal specimens were culture for L. casei Shirota (SHIROTA strain) using LLV-FOS culture medium and enumeration of L. casei Shirota (SHIROTA strain) was calculated. All stool samples were also tested for the presence of L. casei Shirota (SHIROTA strain) by using nested PCR to confirm the presence of L. casei Shirota (SHIROTA strain) obtained from culture method.
Results: Both culture and nested PCR method showed that all the stools samples obtained from subjects prior to the administration of L. casei Shirota (SHIROTA strain) containing milk product were devoid of L. casei Shirota (SHIROTA strain) , except for 3 specimens which showed weakly positive test for PCR. At 7 days after ingesting L. casei Shirota (SHIROTA strain) containing milk product, all stool specimens were positive for L. casei Shirota (SHIROTA strain) on both culture and PCR method. At 7 days after stopped taking L. casei Shirota (SHIROTA strain) containing milk product, 1/19 specimens were positive from culture and 6/ 19 specimens were positive for PCR method.
Conclusion: L. casei Shirota (SHIROTA strain) could survive in the gastrointestinal tract of Thai subjects and could be recovered from the feces after ingestion.
Methods and Results: Twenty healthy volunteers took part in a double-blind placebo-controlled probiotic feeding study (10 fed probiotic, 10 fed placebo). The probiotic was delivered in two 65 ml aliquots of fermented milk drink (FMD) daily for 21 days at a dose of 8.6 +/- 0.1 Log(10) Lact. casei CFU ml(-1) FMD. Faecal samples were collected before, during and after FMD or placebo consumption, and important groups of faecal bacteria enumerated by fluorescent in situ hybridization (FISH) using oligonucleotide probes targeting the 16S rRNA. The fed Lact. casei was enumerated using selective nutrient agar and colony identity confirmed by pulsed field gel electrophoresis. Seven days after ingestion of FMD, the Lact. casei was recovered from faecal samples taken from the active treatment group at 7.1 +/- 0.4 Log(10) CFU g(-1) faeces (mean +/- SD, n = 9) and numbers were maintained at this level until day 21. Lact. casei persisted in six volunteers until day 28 at 5.0 +/- 0.9 Log(10) CFU g(-1) faeces (mean +/- SD, n = 6). Numbers of faecal lactobacilli increased significantly upon FMD ingestion. In addition, the numbers of bifidobacteria were higher on days 7 and 21 than on days 0 and 28 in both FMD fed and placebo fed groups. Consumption of Lact. casei had little discernible effect on other bacterial groups enumerated.
Conclusions: Daily consumption of FMD enabled a probiotic Lact. casei strain to be maintained in the gastrointestinal tract of volunteers at a stable relatively high population level during the probiotic feeding period.
Significance and Impact of the Study: The study has confirmed that this probiotic version of Lact. casei survives well within the human gastrointestinal tract.
Methods: A total of seventeen healthy subjects were randomised to either a probiotic (n=8) or a control (n=9) group. The probiotic group consumed a LcS -fermented milk drink twice daily for 4 weeks whereas the control group received no supplementation. Subjects maintained their normal diet for the first 3 weeks of the study, after which they consumed a high-fat (65% of energy), high-energy (50% increase in energy intake) diet for 7 days. Whole-body insulin sensitivity was assessed by an oral glucose tolerance test conducted before and after overfeeding.
Results: Body mass was increased by 0·6 (SE 0·2) kg in the control group (P<0·05) and by 0·3 (SE 0·2) kg in the probiotic group (P>0·05). Fasting plasma glucose concentrations increased following 7 days of overeating (control group: 5·3 (SE 0·1) v. 5·6 (SE 0·2) mmol/l before and after overfeeding, respectively, P<0·05), whereas fasting serum insulin concentrations maintained in both groups. Glucose AUC values increased by 10% (from 817 (SE 45) to 899 (SE 39) mmol/l per 120 min, P<0·05) and whole-body insulin sensitivity decreased by 27% (from 5·3 (SE 1·4) to 3·9 (SE 0·9), P<0·05) in the control group. Normal insulin sensitivity was maintained in the probiotic group (4·4 (SE 0·8) and 4·5 (SE 0·9) before and after overeating respectively (P>0·05). Conclusions: These results suggest that probiotic supplementation may be useful in the prevention of diet-induced metabolic diseases such as type 2 diabetes.
Methods and Results: DIO mice were fed a high-fat diet without or with 0•05% L. casei Shirota (SHIROTA strain) for 4 weeks and then subjected to an insulin tolerance test (ITT) or oral glucose tolerance test (OGTT). Oral administration of L. casei Shirota (SHIROTA strain) not only accelerated the reduction in plasma glucose levels during the ITT, but also reduced the elevation of plasma glucose levels during the OGTT. In addition, plasma levels of lipopolysaccharide-binding protein (LBP), which is a marker of endotoxaemia, were augmented in the murine models of obese DIO, ob/ob, db/db and KK-A(y) and compared to those of lean mice. L. casei Shirota (SHIROTA strain) treatment suppressed the elevation of plasma LBP levels in DIO mice, but did not affect intra-abdominal fat weight.
Conclusions: L. casei Shirota (SHIROTA strain) improves insulin resistance and glucose intolerance in DIO mice. The reduction in endotoxaemia, but not intra-abdominal fat, may contribute to the beneficial effects of L. casei Shirota (SHIROTA strain) .
Significance and Impact of the Study: This study suggests that L. casei Shirota (SHIROTA strain) has the potential to prevent obesity-associated metabolic abnormalities by improving insulin resistance.
Aim: Although several studies have demonstrated the efficacy of probiotics for preventing upper respiratory tract infections (URTIs) in at-risk populations, including children and the elderly. Few studies have investigated the efficacy of probiotics in healthy adults living normal, everyday lives. Thus, this study evaluated the effect of Lactobacillus casei strain Shirota-fermented milk (L. casei Shirota (SHIROTA strain) -FM) on the incidence of URTIs in healthy middle-aged office workers.
Method: In a randomized controlled trial, 96 male workers aged 30–49 years consumed LcS -FM containing 1.0 × 1011 L. casei Shirota (SHIROTA strain) bacteria or control milk (CM) once daily for 12 weeks during the winter season. URTI episodes were evaluated by a physician via a questionnaire of URTI symptoms.
Results: The incidence of URTIs during the intervention period was significantly lower in the L. casei Shirota (SHIROTA strain) -FM group as compared to the CM group (22.4 vs. 53.2 %, P = 0.002). The time to-event analysis showed that the L. casei Shirota (SHIROTA strain) -FM group had a significantly higher URTI-free rate than the CM group over the test period (log-rank test: χ2 11.25, P = 0.0008). The cumulative number of URTI episodes and cumulative days with URTI symptoms per person was lower in the L. casei Shirota (SHIROTA strain) -FM group, and the duration per episode was shorter. Inhibition of both reductions in NK cell activity in peripheral blood mononuclear cells and increase in salivary cortisol levels was observed in the L. casei Shirota (SHIROTA strain) -FM group.
Conclusions: The results suggest that the daily intake of fermented milk with L. casei Shirota (SHIROTA strain) may reduce the risk of URTIs in healthy middle-aged office workers, probably through modulation of the immune system.
Aim: There is insufficient evidence of preventive effect of probiotics on upper respiratory tract infections (URTIs) in an elderly population.
Method: A multicenter, double-blinded, randomized, placebo-controlled parallel group study was conducted. Elderly persons had participated who used day care at 4 facilities in Tokyo. We used fermented milks containing Lactobacillus casei strain Shirota (L. casei Shirota (SHIROTA strain) ) and placebo drinks as test drinks.
Results: A total of 154 subjects was analyzed. The number of persons diagnosed with an acute URTIs was almost identical in both groups (L. casei Shirota (SHIROTA strain) : 31, placebo: 32), whereas the number of acute URTIs events (L. casei Shirota (SHIROTA strain) : 68, placebo: 51) and the symptom score (L. casei Shirota (SHIROTA strain) : 425, placebo: 396) were both higher in the L. casei Shirota (SHIROTA strain) group. Permutation tests performed using the total number of acute URTIs infection events/total days of observation and the total symptom score/total days of observation found no statistically significant difference respectively (P values of .89 and .64, respectively). Comparing the mean duration of infection per infection event found a shorter mean duration in the L. casei Shirota (SHIROTA strain) group (L. casei Shirota (SHIROTA strain) : 3.71 days, placebo: 5.40 days), and the difference was statistically significant.
Conclusions: The results suggest that fermented milk containing L. casei Shirota (SHIROTA strain) probably reduces the duration of acute URTIs.
The use of probiotics as dietary approach to prevent exposure to food contaminant, aflatoxin B1 (AFB1) has greatly increased. Several studies found that AFB1 binding to the bacterial cell wall is strain-specific. Moreover, the interaction between AFB1 and bacterial cell wall is not well-understood, thus warrants further investigation. This research was conducted to assess the ability of Lactobacillus casei Shirota L. casei Shirota (SHIROTA strain) to bind AFB1 at different concentrations and to determine AFB1 binding efficiency of different L. casei Shirota (SHIROTA strain) cell components including live cell, heat-treated, and cell wall. In addition, the interaction between AFB1 and L. casei Shirota (SHIROTA strain) was also evaluated via scanning electron microscopy (SEM) and through an animal study. The binding of AFB1 by all L. casei Shirota (SHIROTA strain) cell components depends on the concentration of available AFB1. Among all L. casei Shirota (SHIROTA strain) cell components, the live L. casei Shirota (SHIROTA strain) cells exhibited the highest binding efficiency (98%) toward AFB1. Besides, the SEM micrographs showed that AFB1 induced structural changes on the bacterial cell surface and morphology including rough and irregular surface along with a curve rod-shaped. In vivo experiment revealed that L. casei Shirota (SHIROTA strain) is capable of neutralizing the toxicity of AFB1 on body weight and intestine through the binding process. The animal's growth was stunted due to AFB1 exposure, however, such effect was significantly (p < 0.05) alleviated by LcS. This phenomenon can be explained by a significant (p < 0.05) decreased level of blood serum AFB1 by L. casei Shirota (SHIROTA strain) (49.6 ± 8.05 ng/mL) compared to AFB1-exposed rats without treatment (88.12 ± 10.65 ng/mL). Taken together, this study highlights the potential use of L. casei Shirota (SHIROTA strain) as a preventive agent against aflatoxicosis via its strong binding capability.
Considerate proportion of elderly patients with a rib fracture are susceptible to pulmonary complications, especially pneumonia. This study aimed to assess the effect of oral administration of the probioticLactobacillus casei ShirotaL. casei Shirota (SHIROTA strain) on pneumonia and pulmonary functions among elderly patients with single rib fracture. The current study included 204 eligible elderly patients with a single rib fracture. Patients were randomly assigned to receive oral administration of skimmed milk containing either a commercial probiotic L. casei Shirota (SHIROTA strain) or placebo daily for 1 month after the fracture. This was followed by pneumonia assessments, pulmonary function testing including forced expiratory volume (FEV), negative inspiratory pressure (NIP), and forced vital capacity (FVC), as well as evaluation of potential adverse effects including myocardial infarction, acute kidney injury, nonunion of fractured bone, or stroke. After 1-month consumption, patients in the L. casei Shirota (SHIROTA strain) group exhibited decreased pneumonia and increased recovery of pulmonary functions, in terms of FEV, FVC, and NIP, compared to the placebo group. No difference was observed in incidence of adverse events between the 2 groups. In patients with a single rib fracture, oral administration of the probiotic L. casei Shirota (SHIROTA strain) was associated with a lower incidence of pneumonia and increased pulmonary functions without causing severe adverse effects.
Suppression of immune function during long spaceflights is an issue that needs to be overcome. The probiotic Lactobacillus casei strain Shirota (LcS) could be a promising countermeasure, and a project was launched to investigate the efficacy of its use on the International Space Station (ISS). As a first step, a special probiotic product for space experiments, containing freeze-dried L. casei Shirota (SHIROTA strain) in capsule form (probiotics package) was developed. This was for tested its stability through 1 month of storage on the ISS. The temperature inside the ISS ranged from 20.0 to 24.5 °C. The absorbed dose rate of the flight sample was 0.26 mGy/day and the dose equivalent rate was 0.52 mSv/day. The number of live L. casei Shirota (SHIROTA strain) was 1.05 × 1011 colony-forming units/g powder (49.5% of the initial value) 6 months after the start of the study; this value was comparable to those in the two ground controls. Profiles of randomly amplified polymorphic DNA, sequence variant frequency, carbohydrate fermentation, reactivity to LcS-specific antibody, and the cytokine-inducing ability of L. casei Shirota (SHIROTA strain) in the flight sample did not differ from those of the ground controls.
Evidence suggests that the gut microbiota might play an important role in fibromyalgia syndrome (FMS) and chronic fatigue syndrome (CFS). The goal of the study was to systematically review the reported effect of probiotic treatments in patients diagnosed with FMS or CFS. A systematic review was carried out using 14 databases (PubMed, Cochrane Library, Scopus, PsycINFO, and others) in February 2016 to search for randomised controlled trials (RCTs) and pilot studies of CFS or FMS patient, published in the last ten years (from 2006 to 2016). The Jadad scale was used to asseverate the quality of the clinical trials considered. Two studies (n=83) met the inclusion criteria, which were performed in CFS patients and both studies were considered as a 'High range of quality score'. The administration of Lactobacillus casei strain Shirota in CFS patients, over the course of 8 weeks, reduced anxiety scores. Likewise, this probiotic changed the faecal composition following 8 weeks of treatment. Additionally, the treatment with Bifidobacterium infantis 35624 in CFS patients, during the same period, reduced inflammatory biomarkers. The evidence about the usefulness of probiotics in CFS and FMS patients remains limited. The studied strains of probiotics have demonstrated a significant effect on modulating the anxiety and inflammatory processes in CFS patients. However, more experimental research, focusing mainly on the symptoms of the pathologies studied, is needed.
The study aimed to examine whether Lactobacillus casei strain Shirota L. casei Shirota (SHIROTA strain) improves sleep quality under psychological stress. A double-blind, placebo-controlled trial was conducted in healthy fourth year medical students exposed to academic examination stress. The trial was repeated over two consecutive years in different groups of students, and the data were pooled. For 8 weeks prior to and 3 weeks after a National Standardized Examination, a total of 48 and 46 subjects received a daily dose of 100 ml of LcS-fermented milk or non-fermented placebo milk, respectively. The study measured subjective anxiety, overnight single-channel electroencephalography (EEG) recordings, and the Oguri-Shirakawa-Azumi (OSA) sleep inventory scores of subjective sleeps quality. Total OSA scores were significantly lower than baseline on the day before the exam and recovered after the exam, indicating a stress-induced decline in sleep quality. There was a significant positive effect of LcS treatment on OSA factors for sleepiness on rising and sleep length. Sleep latency measured by EEG lengthened as the exam approached in the placebo group but was significantly suppressed in the LcS group. The percentage of stage 3 non-REM (N3) sleep decreased in the placebo group as the exam approached, whereas it was maintained in the LcS group throughout the trial. Delta power during the first sleep cycle, measured as an index of sleep intensity, increased as the exam approached in the LcS group and was significantly higher than in the placebo group. The study suggests that daily consumption of LcS may help to maintain sleep quality during a period of increasing stress. The observed retention of N3 sleep and increased delta power in the LcS group may have contributed to higher perceived sleep satisfaction.
The study was conducted to investigate the effects of the probiotic Lactobacillus casei strain Shirota L. casei Shirota (SHIROTA strain) on abdominal dysfunction, a double-blind, placebo-controlled trial with healthy medical students undertaking an authorized Nationwide examination for academic advancement. 23 and 24 subjects consumed an L. casei strain Shirota-fermented milk and a placebo milk daily, respectively for 8 weeks, until the day before the examination. In addition to assessments of abdominal symptoms, psychophysical state, and salivary stress markers, gene expression changes in peripheral blood leukocytes and composition of the gut microbiota were analyzed using DNA microarray analysis and 16S rRNA gene amplicon sequence analysis, respectively, before and after the intervention. Stress-induced increases in a visual analog scale measuring feeling of stress, the total score of abdominal dysfunction, and the number of genes with changes in expression of more than 2-fold in leukocytes were significantly suppressed in the L. casei strain Shirota group compared with those in the placebo group. A significant increase in salivary cortisol levels before the examination was observed only in the placebo group. The administration of L. casei strain Shirota, but not placebo, significantly reduced gastrointestinal symptoms. Moreover, 16S rRNA gene amplicon sequencing demonstrated that the L. casei strain Shirota group had significantly higher numbers of species, a marker of the alpha-diversity index, in their gut microbiota and a significantly lower percentage of Bacteroidaceae than the placebo group.The study demonstrated that the daily consumption of the probiotic strain L. casei strain Shirota, preserves the diversity of the gut microbiota and may relieve stress-associated responses of abdominal dysfunction in healthy subjects exposed to stressful situations.
Aim: This study investigated relationships between the frequent intake of fermented milk products containing Lactobacillus casei strain Shirota L. casei Shirota (SHIROTA strain) and the onset of hypertension (resting systemic pressure ≥140 mmHg [systolic]/≥90 mmHg [diastolic].
Method: A 5-year period of study was conducted in 352 Japanese who were in the age group of 65 to 93 years, (125 men and 227 women). The subjects were divided into two groups (n=254 and n=98) on the basis of their intake of fermented milk products (less than 3 times a week or more than 3 times a week).
Results: The incidence of hypertension over the 5-year interval was significantly lower in those who took fermented milk products more than 3 times rather than less than 3 times/week (6.1 vs 14.2%, P=0.037). A multivariate-adjusted proportional hazards model predicted that blood pressures were significantly more likely to remain normal over 5 years in subjects who took more than 3 times fermented milk products rather than less than 3 times/ week (relative risk 0.398 [95% confidence interval 0.167-0.948], P=0.037).
Conclusions: These results suggest that after adjustment for potential confounders, the risk of developing hypertension is substantially lower in elderly people who take fermented milk products containing LcS at least 3 times a week.
Aim: To clarify the usefulness of Lactobacillus casei strain Shirota (LcS) - fermented milk in the normalization of bowel movements and improvement of infection control for the elderly residents and staff of facilities for the elderly.
Method: The study was performed on elderly residents (average age, 85) and staff members (average age, 37) of facilities for the elderly. Participants were divided into two groups based on their intake of Lactobacillus casei strain Shirota (LcS) fermented milk or a placebo once daily for 6 months.
Results: A significantly lower incidence of fever and improved bowel movement was seen in the LcS - fermented milk group (n=36) in comparison to the placebo group (n=36). The numbers of Bifidobacterium and Lactobacillus were higher (p < 0.01) whereas pathogenic organisms such as Clostridium difficile were significantly lower (p < 0.05), fecal acetic acid concentration and total acidity was higher in the LcS group. A significant difference in the intestinal microbiota, fecal acetic acid, and pH was also observed between the LcS and placebo groups among the staff members.
Aim: To determine whether a fermented milk drink containing probiotics could improve the bowel habits of frail elderly individuals living in a nursing home.
Method: The bowel habit (stool quality and bowel movements) of 135 participants was recorded by nursing staff during a baseline period of 3 weeks. After this period participants received daily a fermented milk drink containing minimally 6.5×109 colony forming units of Lactobacillus casei Shirota (LcS) for 6 weeks. During this period, bowel habits was recorded and compared to baseline period. 44 participants (74-99 years old) was compliant and used for analysis.
Results: Consumption of fermented milk containing LcS significantly increased the percentage of ideal stool types per week (P<0.01), lowered the percentage of constipation stool types per week (P<0.01) and significantly lowered the percentage of diarrhoea stool types per week (P=0.016) as compared to the baseline period.
Conclusions: The results suggest that a fermented milk containing LcS significantly improves the bowel habits of frail elderly residents in a nursing home. The results of this study need further substantiation.
Conclusions: The study concludes that long-term consumption of LcS -fermented milk may be useful in decreasing the daily risk of infection and improving the quality of life among the residents and staff in facilities for the elderly.
Aim: This pilot study investigated the effects of the probiotic Lactobacillus casei strain Shirota (L. casei Shirota (SHIROTA strain) ) on psychological and physical stress responses in medical students undertaking an authorized Nationwide examination for promotion.
Method: In a double-blind, placebo-controlled trial, 24 and 23 healthy medical students consumed a fermented milk containing LcS and a placebo milk, respectively, once a day for 8 weeks until the day before the examination. Psychological state, salivary cortisol, faecal serotonin and plasma L-tryptophan were analysed on 5 different sampling days (8 weeks before examination, 2 weeks before examination, 1 day before examination, immediately after examination and 2 weeks after the examination). Physical symptoms were also recorded in a dairy by subjects during the intervention period for 8 weeks.
Results: In association with a significant elevation of anxiety at 1 day before the examination, salivary cortisol and plasma L-tryptophan levels were significantly increased in only the placebo group (P < 0.05). Two weeks after the examination, the L. casei Shirota (SHIROTA strain) group had significantly higher faecal serotonin levels (P < 0.05) than the placebo group. Moreover, the rate of subjects experiencing common abdominal and cold symptoms and total number of days experiencing these physical symptoms per subject were significantly lower in the L. casei Shirota (SHIROTA strain) group than in the placebo group during the pre-examination period at 5-6 weeks (each P < 0.05) and 7-8 weeks (each P < 0.01) during the intervention period.
Conclusions: The results suggest that daily consumption of fermented milk containing L. casei Shirota (SHIROTA strain) may exert beneficial effect by preventing the onset of physical symptoms in healthy subjects exposed to stressful situations.
METHODS AND RESULTS:Sprague Dawley rats were divided into three groups of untreated control, the group induced with AFB1 only, and the group given probiotic in addition to AFB1 . In the group induced with AFB1 only, food intake and body weight were reduced significantly. The liver and kidney enzymes were significantly enhanced in both groups induced with AFB1, but they were lower in the group given L. casei Shirota (SHIROTA strain) . AFB1 was detected from all serum samples except for untreated control group's samples. Blood serum level of AFB1 in the group induced with AFB1 only was significantly higher than the group which received probiotic as a treatment (P < 0•05), and there was no significant difference between the control group and the group treated with probiotic.
CONCLUSIONS:L. casei Shirota (SHIROTA strain) supplementation could improve the adverse effect of AFB1 induction on rats' body weight, plasma biochemical parameters and also could reduce the level of AFB1 in blood serum.
SIGNIFICANCE AND IMPACT OF THE STUDY:This study's outcomes contribute to better understanding of the potential of probiotic to reduce the bioavailability of AFB1. Moreover, it can open an opportunity for future investigations to study the efficacy of oral supplementation of probiotic L. casei Shirota (SHIROTA strain) in reducing aflatoxin level in human.
METHODS:We conducted a multicenter, double-blinded, randomized, placebo-controlled parallel group study. Elderly persons had participated who used day care at 4 facilities in Tokyo. We used fermented milks containing Lactobacillus casei strain Shirota (L. casei Shirota (SHIROTA strain) ) and placebo drinks as test drinks.
RESULTS:A total of 154 subjects was analyzed. The number of persons diagnosed with an acute URTIs was almost identical in both groups (L. casei Shirota (SHIROTA strain) : 31, placebo: 32), whereas the number of acute URTIs events (L. casei Shirota (SHIROTA strain) : 68, placebo: 51) and the symptom score (L. casei Shirota (SHIROTA strain) : 425, placebo: 396) were both higher in the L. casei Shirota (SHIROTA strain) group. Permutation tests performed using the total number of acute URTIs infection events/total days of observation and the total symptom score/total days of observation found no statistically significant difference respectively (P values of .89 and .64, respectively). Comparing the mean duration of infection per infection event found a shorter mean duration in the L. casei Shirota (SHIROTA strain) group (L. casei Shirota (SHIROTA strain) : 3.71 days, placebo: 5.40 days), and the difference was statistically significant.
CONCLUSION:The results suggest that fermented milk containing L. casei Shirota (SHIROTA strain) probably reduces the duration of acute URTIs.
RATIONALE: As lactobacilli can metabolise phenylalanine into phenylacetate, the study was based on the hypothesis that supplementation with L. casei Shirota could help to regulate ammonia metabolism in healthy people undertaking strenuous exercise via the natural generation of phenylacetate by the probiotic. This would enable ammonia, trapped as glutamine, to be excreted as phenylacetylglutamine via the kidneys.
METHOD: An open-label, pilot, proof of principle study was conducted in 20 male football players assigned to consume either probiotic (L. casei Shirota; minimum 6.5x109 twice per day) or no supplementation. The players undertook an exhaustive routine designed to exercise all the major muscle blocks (two cycles of a 9-station static exercise program with a one minute rest between the two cycles; water supplied ad libertum). The players provided a four hour timed urine sample after the exercise program. Both the exercise program and urine sampling were repeated after one month. Urine samples were measured for phenyacetylglutamine and ammonia and corrected by creatinine levels.
RESULTS: The results (expressed as the difference in urinary levels for each volunteer between the two sampling points) showed that phenylacetylglutamine significantly increased in the probiotic group (2.98 ±1.04 vs -0.911 ±0.477; P less than 0.01) and, while not reaching statistical significance, their ammonia levels were also lower compared to the control group (0.953 ± 0.868 vs 1.486 ± 0.865; P=0.064).
CONCLUSIONS: The researchers concluded that probiotic supplementation with a probiotic Lactobacillus strain appeared to help regulate exercise-generated ammonia in young health sportsmen.
There was no exclusion of any particular antibiotic. Antibiotics taken included penicillins, cephalosporins, quinolones, clindamycin, vancomycin, and were multiple as well as single antibiotic regimes.
During probiotic intake, all patients on the ward were offered probiotic, as well as the staff. During periods on the wards of no probiotic intake, neither staff nor patients took probiotic.
AAD:* 17/340 (5%) in L. casei Shirota (SHIROTA strain) group vs 63/338 (18.6%) control group (P less than 0.001)
CDI*: 1/340 (0.3%) in L. casei Shirota (SHIROTA strain) group vs 21/338 (6.2%) control group (P less than 0.001)
Faecal analysis showed that antibiotic therapy decreased abundance of total bacteria, Bifidobacterium spp, Clostridium clusters IV and XI whereas Enterobacteriaceae increased. L. casei Shirota (SHIROTA strain) intervention reduced the observed antibiotic-induced decrease in abundance of total bacteria and Bifidobacterium. L. casei Shirota (SHIROTA strain) intervention also increased Lactobacillus abundance.
*Antibiotic-associated diarrhoea = AAD; C. difficile infection = CDI
Methods: Nine HD patients received SYN ( Lactobacillus casei strain Shirota and Bifidobacterium breve strain Yakult as probiotics and galacto-oligosaccharides as prebiotics) three times a day for 2 weeks. The duration of the study was 4 weeks (2 weeks of pretreatment observation and 2 weeks of treatment). The subjects were asked to complete a questionnaire about their bowel habits (defecation frequency, stool quantity, stool form and ease of defecation) during the study period. Serum p-cresol levels before and after SYN treatment were determined.
Results: According to the questionnaire conducted during the pretreatment observation period, HD patients with a high serum p-cresol level tended to have hard stools with difficulty in defecation. With SYN treatment, stool quantity increased significantly and hard, muddy or soft stools tended to be replaced by normal ones. The serum p-cresol level also decreased significantly.
Conclusions: It was found that uraemic toxin, p-cresol, was associated with constipation and that SYN treatment resulted in normalization of bowel habits and a decrease of serum p-cresol levels in HD patients. Therefore, SYN treatment may be anticipated to reduce the toxic effect of p-cresol in HD patients.
Aim: To evaluate the effects of a 4-week consumption of a probiotic product containing Lactobacillus casei Shirota and Bifidobacterium breve Yakult (10(7)-10(9) CFU of each strain) on symptoms and breath hydrogen exhalation after a lactose load in lactose-intolerant patients and whether the beneficial results persisted after probiotic discontinuation.
Methods: Twenty-seven patients with lactose maldigestion and intolerance participated in this study, which comprised 4 hydrogen breath tests: baseline condition (20 g lactose), after lactase ingestion (9000 FCC units), at the end of 4-week probiotic supplementation, and a follow-up test performed 3 months after probiotic discontinuation. For each test, the area under the breath hydrogen concentration vs time curve (AUC (180 min)) was calculated, and symptom scores were recorded.
Results: The probiotic combination significantly reduced symptom scores (P < .01) and breath hydrogen AUC (P=.04) compared with the baseline condition. The comparison with the lactase test showed that symptom scores were similar (P> .05), despite the significantly higher (P = .01) AUC values after probiotic use. In the follow-up test, symptom scores and breath hydrogen AUC values remained similar to those found at the end of probiotic intervention.
Conclusion: Four-week consumption of a probiotic combination of L casei Shirota and B breve Yakult seems to improve symptoms and decrease hydrogen production intake in lactose-intolerant patients. These effects may persist for at least 3 months after suspension of probiotic consumption
Subjects / Methods: Patients with MetS were randomized to receive 3 × 6.5 × 10 CFU L. casei Shirota (probiotic group) or not for 3 months. Gut permeability was assessed by a differential sugar absorption method and by determination of diaminooxidase serum levels, endotoxin by an adapted limulus amoebocyte lysate assay, neutrophil function and toll-like receptor (TLR) expression by flow cytometry and ELISA was used to detect lipopolysaccharide-binding protein (LBP) and soluble CD14 (sCD14) levels.
Results: Twenty-eight patients and 10 healthy controls were included. Gut permeability was significantly increased in MetS compared with controls but did not differ between patient groups. None of the patients were positive for endotoxin. LBP and sCD14 levels were not significantly different from healthy controls. High-sensitive C-reactive protein and LBP levels slightly but significantly increased after 3 months within the probiotics group. Neutrophil function and TLR expression did not differ from healthy controls or within the patient groups.
Conclusions: Gut permeability of MetS patients was increased significantly compared with healthy controls. L. casei Shirota administration in the MetS patients did not have any influence on any parameter tested possibly due to too-short study duration or underdosing of L. casei Shirota.
Material and Method: Time-kill methods of FMLC and cell-free filtered fluid of FMLC (CF-FMLC) against Acinetobacter baumannii, Pseudomonas aeruginosa, ESBL-producing Escherichia coli & Klebsiella pneumoniae and methicillin-resistant Staphylococcus aureus were conducted. The control solutions were Mueller Hinton broth (MHB) and distilled water. The mixtures of FMLC, CF-FMLC, MHB and DW with 10(5) to 10(6) CFU/ml of each bacterium were prepared and incubated at 35 degrees C. Each mixture was quantified for viable bacteria at 0, 1, 3, 6 and 24 hr after incubation onto brain heart infusion agar plates. The inoculated agar plates were incubated at 35 degrees C for 24-48 hr. Bacterial colonies on agar plates were counted and compared among the mixtures.
Results: Log CFUs of each organism in MHB and distilled water after incubation were increased from 5.1-6.3 at 0 h to 6.4- > 11 at 24 hr. Log CFUs of each organism in FMLC and CF-FMLC after incubation with study bacteria for 0, 1, 3, 6 and 24 hr were decreased to undetectable amounts at 24 hr.
Conclusion: FMLC and CF-FMLC exerted slow inhibitory activity against MDR bacteria resulting in eradication of all study bacteria at 24 hr. Such inhibitory effects were probably due to the products of the milk fermented by Lactobacillus casei strain Shirota. Clinical study is needed to determine if consumption of FMLC can prevent and treat colonization and infection with MDR bacteria in hospitalized patients.