1.
Efficacy and dose response of Lactiplantibacillus plantarum in diarrhea-predominant irritable bowel syndrome.
Martoni, CJ, Srivastava, S, Damholt, A, Leyer, GJ
World journal of gastroenterology. 2023;29(28):4451-4465
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Plain language summary
Probiotics are microorganisms that have been shown in previous research to improve symptoms of diarrhoea-predominant irritable bowel syndrome (IBS-D). This randomised control trial of 307 individuals with IBS-D aimed to determine the tolerability and efficacy of varying doses of the microbiota Lactiplantibacillus plantarum. The results showed that the severity of symptoms improved with L. plantarum regardless of whether individuals were given a high or low dose. Improvements were seen as soon as 28 days following supplementation. Abdominal pain severity, duration, bloating, bowel movements, and quality of life were all improved. Individuals in the study largely tolerated the supplement, with only a few occurrences of nausea and vomiting. It was concluded that L. plantarum is effective and safe for improving symptoms associated with IBS-D. This study could be used by healthcare professionals to recommend L. plantarum supplementation to individuals with hard to treat or persistent IBS-D.
Expert Review
Conflicts of interest:
None
Take Home Message:
- This randomised, double-blind, placebo controlled, multi-centre, parallel-arm and dose-ranging study showed that L. plantarum may be a strong candidate for the management of IBS-D symptoms and associated mental health effects.
- L. plantarum may be of particular benefit to individuals who are suffering from stress because of IBS-D.
- L. plantarum is well tolerated and may be of benefit to individuals who have ceased pharmaceutical treatments as a result of side-effects.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
This study aimed to determine the tolerability and efficacy of varying supplemental doses of Lactiplantibacillus plantarum (Lpla33) in adults with irritable bowel syndrome of the diarrhoea predominant subtype (IBS-D).
Methods
This randomised, double blind, placebo-controlled trial recruited 307 females and males aged 18-70 years with IBS-D based upon the Rome IV diagnostic criteria with Bristol Stool Scale stools of type 6 or 7.
Individuals were randomised to receive an eight-week intervention in one of three study groups: Group 1B: Lpla33 at 1 × 109 vs group 10B: 1x1010 colony forming units (CFU) per day vs placebo.
Results
- Improvement was seen in the primary outcome of IBS-D symptom severity (IBS-SSS) with both Lpla33 doses compared to placebo at the end of the trial (P=<0.001).
- Improvements with both doses compared to placebo were seen as quickly as 28 days (P=<0.01).
- At the end of the study the higher dose Lpla33 was more effective at improving IBS-SSS compared to the lower dose (P=<0.05).
- Improvements to IBS remission or mild IBS were seen in 48.1% in group 1B, 72.6% in group 10B and only 11.1% of placebo (P=<0.001).
- Specific improvements were seen in 10B group compared to placebo in abdominal pain severity and duration, abdominal distension, bowel habits, and quality of life (QoL) (P=<0.001).
- Post-hoc analysis showed that supplementation prevented symptom development compared to placebo with 2.9% of group 1B, 2.1% of group 10B and 18.2% of placebo individuals reporting increased symptom severity (P=<0.001).
- QoL and perceived stress were improved with supplementation compared to placebo (P=<0.001 for both), with the higher dose being more beneficial than the lower dose in QoL (P=<0.001).
- Compliance to Lpla33 was comparable to placebo (P=>0.05), with adverse events related to the supplement including nausea and vomiting.
Conclusion
- L. plantarum at doses of 1 × 109 and 1 × 1010 CFU/day is a well-tolerated and efficacious therapy for the improvement of symptoms related to IBS-D, with benefits seen as quickly as 28 days after commencing supplementation.
- Symptoms such as abdominal pain severity and duration, QoL and perceived stress may all be improved.
- Stool normalisation may be seen in certain individuals.
Clinical practice applications:
- L. plantarum supplementation may be of benefit to the management and improvement of symptoms in individuals with IBS-D.
- Improvements may be seen physically and in mental health parameters.
- Metronidazole (400mg/day) was given as a rescue medication for individuals with severe pain and frequent loose stools and should be considered when interpreting results.
Considerations for future research:
- The authors concluded that future research should focus on understanding the mechanisms of action that may be involved.
- Studying the role of diet on the microbial community and metabolite profiles in IBS-D may be of interest.
Abstract
BACKGROUND Probiotics have shown promise in alleviating symptoms of diarrhea-predominant irritable bowel syndrome (IBS-D); however, the certainty of evidence is low. Well-powered randomized controlled dose-ranging trials are warranted on promising single-strain candidates. AIM: To investigate the clinical efficacy of Lactiplantibacillus plantarum (L. plantarum) Lpla33 (DSM34428) in adults with IBS-D. METHODS This is a randomized, double-blind, placebo-controlled, multi-center, and dose-ranging study. Three hundred and seven adults, 18-70 years of age, with IBS-D, according to Rome IV criteria, were allocated (1:1:1) to receive placebo or L. plantarum Lpla33 at 1 × 109 (1B) or 1 × 1010 (10B) colony-forming units/d over an 8-wk intervention period. The primary outcome was the change in IBS severity scoring system (IBS-SSS) total score after 8 wk, while secondary and exploratory outcomes included abdominal pain severity, IBS related quality of life, stool and microbial profile, and perceived stress. RESULTS IBS-SSS was significantly reduced, after 8 wk, in participants receiving L. plantarum 1B (-128.45 ± 83.30; P < 0.001) and L. plantarum 10B (-156.77 ± 99.06; P < 0.001), compared to placebo (-58.82 ± 74.75). Further, a dose-ranging effect was observed, with a greater absolute reduction in the L. plantarum 10B group (P < 0.05). A reduction in sub-scores related to abdominal pain, abdominal distension, bowel habits, and quality of life was observed in both L. plantarum groups compared to placebo (P < 0.001). Further, 62.5% and 88.4% of participants administered L. plantarum 1B and 10B, respectively, were classified as stool consistency responders based on a reduction in diarrheal stool form, as compared to 26.3% in the placebo group (P < 0.001). In contrast, no significant shifts were observed in microbial diversity. CONCLUSION L. plantarum Lpla33 (DSM34428) is well tolerated and improves IBS symptom severity with a dose-ranging effect and a corresponding normalization of bowel habits in adults with IBS-D.
2.
Effects of Lactococcus lactis subsp. cremoris YRC3780 daily intake on the HPA axis response to acute psychological stress in healthy Japanese men.
Matsuura, N, Motoshima, H, Uchida, K, Yamanaka, Y
European journal of clinical nutrition. 2022;76(4):574-580
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Plain language summary
The hypothalamic-pituitary-adrenal (HPA) axis is involved in the stress response and is linked to the microbiome through a number of possible mechanisms, including immune-related ones. Lactococcus lactis subsp. cremoris YRC3780 (YRC3780), a probiotic isolated from kefir, has been shown to have beneficial immune-modulatory properties. The aim of this double-blind, placebo-controlled trial, which included 27 healthy young men, was to assess sleep quality, mental health, HPA axis activity (salivary cortisol) and response to an acute stress test during/after 8 weeks of supplementation with YRC3780. At 8 weeks, salivary morning cortisol levels were significantly reduced in the probiotic compared to the placebo group. The effect on the stress test depended on whether or not participants were considered “cortisol-responders” or not. Improvements in sleep quality were seen at 6 weeks (but not at any other time points) in 1 out of 2 sleep questionnaires in the YRC3780 group, whilst no significant differences were observed in actigraphy-measured sleep efficiency. There were no differences in mood between groups, but significant improvements in general health in the probiotic group. Interestingly, no changes in the microbiome of the probiotic group were seen, suggesting that the observed effects may be mediated via the immune system.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Research indicates a bidirectional interaction between the gut microbiome and the central nervous system, affecting the functions of the brain and spinal cord.
- This clinical trial suggests that daily intake of Lactococcus lactis subsp. cremoris (YRC3780) may enhance the HPA axis response to acute psychological stress, potentially linked to a reduction in morning cortisol levels.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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X
B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
A randomized, placebo-controlled, double-blind clinical trial was conducted to investigate the influence of Lactococcus lactis subsp. cremoris (YRC3780), isolated from kefir, on stress response, sleep quality, and mental health.
Method
Twenty-seven healthy young men, with an average age of 23.5 years, and mean body mass index of 21.5 kg/m2 , were randomly assigned to either the YRC3780 group or the placebo group. Participants were administered YRC3780 or a placebo daily for 8 weeks.
Throughout the study, participants completed assessments, including the Athens Insomnia Scale (AIS), the Pittsburgh Sleep Quality Index (PSQI), the General Health Questionnaire (GHQ-28), and the Profile of Mood States 2nd Edition-Adult Short, Total Mood Disturbance subscale (POMS 2 TMD), every 2 weeks. Additionally, diurnal rhythms of HPA axis activity were assessed every 2 weeks through saliva samples collected at 2-hour intervals during the day. At the end of the 8-week supplementation period, participants underwent the Trier Social Stress Test (TSST) to evaluate the effects of daily YRC3780 intake on the HPA axis stress response. In addition, three fecal samples were collected to analyse the gut microbiome (on the last day of baseline, and at 4 and 8 weeks).
A total of 27 out of 33 subjects (81%) completed the study, with six participants withdrawing without providing explanations.
Results
The primary findings of this study were as follows:
- At week 6 of YRC3780 supplementation, salivary cortisol levels at 2 hours and 6 hours after waking were significantly lower in the YRC3780 group compared to the placebo group (p=0.05).
- Salivary cortisol concentrations at 40 minutes after the TSST were significantly lower in the YRC3780 group (4.2 ± 4.4 nmol/L, mean ± SD) than in the placebo group (7.6 ± 4.7 nmol/L) (p=0.043).
- AIS scores at 6 weeks and GHQ-28 scores at 8 weeks were significantly lower in the YRC3780 group compared to the placebo group (AIS, p=0.031; GHQ-28, p=0.038) indicating better sleep quality and a better mental state.
Conclusion:
Oral supplementation with YRC3780 may have beneficial effects on the HPA axis response to acute psychological stress, potentially associated with a decrease in morning cortisol levels. Additionally, the study suggests that the lower basal activity and stress reactivity of the HPA axis may lead to improvements in subjective sleep quality and mental health.
Clinical practice applications:
- The precise mechanisms underlying the correlation between the gut microbiota and the gut-brain axis remain incompletely understood, emphasising the need for further research.
- This clinical trial demonstrated that daily intake of YRC3780 decreased morning salivary cortisol levels at 6 and 8 weeks and reduced the salivary cortisol response to acute psychological stress.
Considerations for future research:
- Larger, adequately powered clinical trials are required to provide deeper insights into the mechanisms responsible for the stress-reducing and sleep-improving effects of Lactococcus lactis subsp. cremoris.
- Furthermore, investigations into optimal dosage and duration of probiotic supplementation are warranted for a more comprehensive understanding, particularly in diverse demographic groups.
- Comparative research is needed to explore the effects of various probiotic strains on objective stress responses.
Abstract
BACKGROUND Lactococcus lactis subsp. cremoris (YRC3780), which is isolated from kefir, has been associated with anti-allergic effects in humans. However, it remains unknown whether daily intake of YRC3780 attenuates the response to psychological stress in humans in parallel with changes to the gut microbiome. We examined the fundamental role of YRC3780 in the gut microbiome, stress response, sleep, and mental health in humans. METHODS Effects of daily intake of YRC3780 on the hypothalamic-pituitary-adrenal (HPA) axis response to acute psychological stress were investigated in a double-blind, placebo-controlled clinical trial involving 27 healthy young men (mean age and body mass index: 23.5 years and 21.5 kg/m2) who were randomly assigned to placebo (n = 13) or YRC3780 (n = 14) groups. The HPA axis response to acute psychological stress, the diurnal rhythm of HPA axis activity, and gut microbiome were assessed and compared between the two groups. RESULTS The results showed that daily intake of YRC3780 significantly lowered morning salivary cortisol levels compared with placebo. In addition, salivary cortisol levels following a social stress test significantly decreased +40 min after beginning the TSST in the YRC3780-treated group compared to placebo. There were no significant differences between the two groups in terms of actigraphy-based sleep quality, but the subjective sleep quality and mental health were significantly improved in the YRC3780-treated group compared to placebo. CONCLUSIONS Our study suggests that daily intake of YRC3780 improves the HPA axis response to acute psychological stress, which might be associated with a decrease in morning cortisol levels.