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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.
Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study.
Kang, DW, Adams, JB, Gregory, AC, Borody, T, Chittick, L, Fasano, A, Khoruts, A, Geis, E, Maldonado, J, McDonough-Means, S, et al
Microbiome. 2017;5(1):10
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Plain language summary
Children with autism spectrum disorders (ASD) often suffer gastrointestinal problems, such as constipation or diarrhea, the severity of which often correlate with ASD severity. This open-label clinical trial evaluated the impact of Microbiota Transfer Therapy (MTT) on GI and ASD symptoms of 18 ASD-diagnosed children. Treatment involved 2 weeks of antibiotic treatment and a bowel cleanse, followed by extended fecal microbiota transplant using a high initial dose and lower maintenance doses for 7-8 weeks. Results showed significant improvements in GI symptoms, which persisted 8 weeks after treatment ended. Bacterial diversity also increased. Behavioural ASD symptoms also improved significantly and lasted 8 weeks after treatment finished. This exploratory study suggests a promising approach to alter the gut microbiome in ASD subjects, improving GI and behavioural symptoms of ASD. Further clinical research is required.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Fecal Microbiota Transfer Therapy demonstrates an effective clinical intervention in pediatric patients suffering with autistic spectrum disorder and associated gastrointestinal symptoms.
- Benefits of the therapy in this trail persisted even 2 months after treatment cessation.
- Future research on autistic spectrum disorder should address microbiota-gut-brain axis.
Evidence Category:
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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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X
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:
The article describes an original clinical protocol in which microbiota transfer was used to ameliorate gastrointestinal (GI) and autism symptoms in pediatric patients. Common occurrence of GI pathology in patients affected by autistic spectrum disorder (ASD), poses a clinical challenge, since there is no standardised specific therapy. In light of recent insights on the importance of microbiota-gut-brain axis in health and disease, microbiota emerges as a salient treatment target in the aforementioned population.
Clinical practice applications:
Fecal microbiota transfer therapy (MTT) applied by the protocol described in the article demonstrates a longer-term effective clinical intervention in pediatric patients suffering from ASD and concomitant GI symptoms. Benefits of the therapy persisted even two months after actual treatment cessation, a highly important feature considering ASD.
Considerations for future research:
This modality could complement current treatments used for ASD-related symptomatology, but requires further validation through additional clinical experiments. The procedure also supports the efforts to focus more research on the role of microbiota in ASD pathophysiology. Further basic and clinical investigations on ASD should include addressing microbiota-gut-brain axis whenever possible, if not always.
Abstract
BACKGROUND Autism spectrum disorders (ASD) are complex neurobiological disorders that impair social interactions and communication and lead to restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. The causes of these disorders remain poorly understood, but gut microbiota, the 1013 bacteria in the human intestines, have been implicated because children with ASD often suffer gastrointestinal (GI) problems that correlate with ASD severity. Several previous studies have reported abnormal gut bacteria in children with ASD. The gut microbiome-ASD connection has been tested in a mouse model of ASD, where the microbiome was mechanistically linked to abnormal metabolites and behavior. Similarly, a study of children with ASD found that oral non-absorbable antibiotic treatment improved GI and ASD symptoms, albeit temporarily. Here, a small open-label clinical trial evaluated the impact of Microbiota Transfer Therapy (MTT) on gut microbiota composition and GI and ASD symptoms of 18 ASD-diagnosed children. RESULTS MTT involved a 2-week antibiotic treatment, a bowel cleanse, and then an extended fecal microbiota transplant (FMT) using a high initial dose followed by daily and lower maintenance doses for 7-8 weeks. The Gastrointestinal Symptom Rating Scale revealed an approximately 80% reduction of GI symptoms at the end of treatment, including significant improvements in symptoms of constipation, diarrhea, indigestion, and abdominal pain. Improvements persisted 8 weeks after treatment. Similarly, clinical assessments showed that behavioral ASD symptoms improved significantly and remained improved 8 weeks after treatment ended. Bacterial and phagedeep sequencing analyses revealed successful partial engraftment of donor microbiota and beneficial changes in the gut environment. Specifically, overall bacterial diversity and the abundance of Bifidobacterium, Prevotella, and Desulfovibrio among other taxa increased following MTT, and these changes persisted after treatment stopped (followed for 8 weeks). CONCLUSIONS This exploratory, extended-duration treatment protocol thus appears to be a promising approach to alter the gut microbiome and virome and improve GI and behavioral symptoms of ASD. Improvements in GI symptoms, ASD symptoms, and the microbiome all persisted for at least 8 weeks after treatment ended, suggesting a long-term impact. TRIAL REGISTRATION This trial was registered on the ClinicalTrials.gov, with the registration number NCT02504554.