-
1.
The effects of Bacillus coagulans MTCC 5856 on functional gas and bloating in adults: A randomized, double-blind, placebo-controlled study.
Majeed, M, Nagabhushanam, K, Paulose, S, Arumugam, S, Mundkur, L
Medicine. 2023;102(9):e33109
-
-
-
Free full text
-
Plain language summary
The reasons for bloating and feelings of stomach discomfort are not fully understood and it is thought that they may be caused by several factors. Amongst these is the possibility that small intestinal bacterial overgrowth (SIBO) and gut microbiota alterations play a role in the development of bloating. Many therapies exist for the symptomatic relief of bloating, however probiotics may be effective for the relief of bloating due to the role of gut microbiota in its development. This randomised control trial of 66 individuals with abdominal bloating, discomfort, and gas aimed to determine the effectiveness of a gut bacteria strain known as Bacillus coagulans MTCC 5856 on feelings of gas and bloating. The results showed that supplementation with B. coagulans MTCC 5856 for 4 weeks relieved feelings of bloating, burping, and gas. It was concluded that B. coagulans MTCC 5856 supplementation was effective at relieving gas and bloating and may be a safe approach for individuals who experience these symptoms. This study could be used by healthcare professionals to recommend B. coagulans MTCC 5856 as a safe and effective therapy for individuals who suffer from gastrointestinal problems such as gas, bloating and stomach discomfort.
Abstract
BACKGROUND Gut microbiome dysbiosis is a major cause of abdominal gas, bloating, and distension. Bacillus coagulans MTCC 5856 (LactoSpore) is a spore-forming, thermostable, lactic acid-producing probiotic that has numerous health benefits. We evaluated the effect of Lacto Spore on improving the clinical symptoms of functional gas and bloating in healthy adults. METHODS Multicenter, randomized, double-blind, placebo-controlled study at hospitals in southern India. Seventy adults with functional gas and bloating with a gastrointestinal symptom rating scale (GSRS) indigestion score ≥ 5 were randomized to receive B coagulans MTCC 5856 (2 billion spores/day, N = 35) or placebo (N = 35) for 4 weeks. Changes in the GSRS-Indigestion subscale score for gas and bloating and global evaluation of patient's scores from screening to the final visit were the primary outcomes. The secondary outcomes were Bristol stool analysis, brain fog questionnaire, changes in other GSRS subscales, and safety. RESULTS Two participants from each group withdrew from the study and 66 participants (n = 33 in each group) completed the study. The GSRS indigestion scores changed significantly (P < .001) in the probiotic group (8.91-3.06; P < .001) compared to the placebo (9.42-8.43; P = .11). The median global evaluation of patient's scores was significantly better (P < .001) in the probiotic group (3.0-9.0) than in the placebo group (3.0-4.0) at the end of the study. The cumulative GSRS score, excluding the indigestion subscale, decreased from 27.82 to 4.42% (P < .001) in the probiotic group and 29.12 to 19.33% (P < .001) in the placebo group. The Bristol stool type improved to normal in both the groups. No adverse events or significant changes were observed in clinical parameters throughout the trial period. CONCLUSIONS Bacillus coagulans MTCC 5856 may be a potential supplement to reduce gastrointestinal symptoms in adults with abdominal gas and distension.
-
2.
The Effect of Probiotic Supplements on Metabolic Parameters of People with Type 2 Diabetes in Greece-A Randomized, Double-Blind, Placebo-Controlled Study.
Zikou, E, Dovrolis, N, Dimosthenopoulos, C, Gazouli, M, Makrilakis, K
Nutrients. 2023;15(21)
-
-
-
Free full text
Plain language summary
Type 2 diabetes is a multifaceted disease caused by both genetic and environmental factors such as excessive energy intake and lack of exercise. The gut microbiome has been shown to contribute to many different diseases including diabetes through its effects on the immune system, appetite, and fat storage. Probiotics are living organisms that have health benefits to humans and they have been studied for their effects on individuals with type 2 diabetes. However, the studies that have been performed have shown inconsistent results due to poorly designed trials. This randomised control trial aimed to determine the effects of a probiotic supplement containing Lactobacillus, Bifidobacterium, and Saccharomyces species on measures of blood sugar control over a period of 6 months. The results showed that compared to controls, there were significant reductions in measures of blood sugar and total cholesterol. Interestingly the probiotics did not change the diversity of the subjects gut microbiome but did alter their function noting changes in enzymes and metabolites involved in diabetes. It was concluded that over a 6-month period, the supplementation of probiotics containing Lactobacillus, Bifidobacterium, and Saccharomyces was of benefit to blood sugar balance and cholesterol levels. This study could be used by healthcare professionals to recommend a specific probiotic to individuals with type 2 diabetes.
Abstract
The role of probiotic supplementation in type 2 diabetes (T2D) treatment is controversial. The present study aimed to assess the effects of a multi-strain probiotic supplement (LactoLevureR (containing Lactobacillus acidophilus, Lactobacillus plantarum, Bifidobacterium lactis, and Saccharomyces boulardii)) over 6 months, primarily on glycemic control as well as on lipid levels and alterations in the gut microbiome, among individuals with T2D residing in Greece. A total of 91 adults with T2D (mean age [±SD] 65.12 ± 10.92 years, 62.6% males) were randomized to receive the probiotic supplement or a matching placebo capsule, once daily, for 6 months. Blood chemistries and anthropometric parameters were conducted every 3 months, and stool samples were collected at baseline and at 6 months. Significant reductions in HbA1c, fasting blood glucose, and total cholesterol were observed in participants treated with the probiotic supplement (n = 46) compared to the controls (n = 45), even after adjustment for a greater decrease in adiposity (waist circumference). Although there were no statistically significant differences in the diversity of the gut microbiome (α and β diversity), the administration of probiotics did influence several genera, metabolites, and key enzymes associated with diabetes. Overall, the administration of the multi-strain probiotic LactoLevureR over a 6-month period in individuals with T2D was well-tolerated and had a positive impact on metabolic parameters, alongside improvements in indices of adiposity.
-
3.
Effect of synbiotic supplementation on immune parameters and gut microbiota in healthy adults: a double-blind randomized controlled trial.
Li, X, Hu, S, Yin, J, Peng, X, King, L, Li, L, Xu, Z, Zhou, L, Peng, Z, Ze, X, et al
Gut microbes. 2023;15(2):2247025
-
-
-
Free full text
-
Plain language summary
The gut microbiota is involved in regulating immunity and synbiotics, that is combinations of pro- and prebiotics, may therefore modulate immunity via the gut microbiota. The aim of this randomised, double-blind, placebo-controlled trial was to evaluate the immune-modulatory effects of a synbiotic supplement (containing Bifidobacterium lactis HN019, Lactobacillus rhamnosus HN001 and fructo-oligosaccharide) in healthy adults. Outcome measures included C-reactive protein (CRP, an inflammatory marker), various pro- and anti-inflammatory cytokines, stool and salivary secretory IgA (sIgA), leukocytes, microbial stool analysis and occurrence, duration, and severity of upper respiratory tract infections (URTI). Compared to the control group, a significant reduction in the inflammatory markers CRP and interferon-gamma and an increase in the anti-inflammatory interleukin-10 and stool sIgA were observed in the supplementation group. There were no differences in types of leukocytes or URTIs between groups. Significant favourable changes in microbiome analysis were observed in the supplemented group which correlated with the observed improvements in inflammatory markers. These changes were dependent on the baseline composition of the microbiome. No adverse events were reported. The authors conclude that the data show that synbiotics are of benefit to healthy adults and support the concept of personalised supplementation.
Abstract
Synbiotics are increasingly used by the general population to boost immunity. However, there is limited evidence concerning the immunomodulatory effects of synbiotics in healthy individuals. Therefore, we conducted a double-blind, randomized, placebo-controlled study in 106 healthy adults. Participants were randomly assigned to receive either synbiotics (containing Bifidobacterium lactis HN019 1.5 × 108 CFU/d, Lactobacillus rhamnosus HN001 7.5 × 107 CFU/d, and fructooligosaccharide 500 mg/d) or placebo for 8 weeks. Immune parameters and gut microbiota composition were measured at baseline, mid, and end of the study. Compared to the placebo group, participants receiving synbiotic supplementation exhibited greater reductions in plasma C-reactive protein (P = 0.088) and interferon-gamma (P = 0.008), along with larger increases in plasma interleukin (IL)-10 (P = 0.008) and stool secretory IgA (sIgA) (P = 0.014). Additionally, synbiotic supplementation led to an enrichment of beneficial bacteria (Clostridium_sensu_stricto_1, Lactobacillus, Bifidobacterium, and Collinsella) and several functional pathways related to amino acids and short-chain fatty acids biosynthesis, whereas reduced potential pro-inflammatory Parabacteroides compared to baseline. Importantly, alternations in anti-inflammatory markers (IL-10 and sIgA) were significantly correlated with microbial variations triggered by synbiotic supplementation. Stratification of participants into two enterotypes based on pre-treatment Prevotella-to-Bacteroides (P/B) ratio revealed a more favorable effect of synbiotic supplements in individuals with a higher P/B ratio. In conclusion, this study suggested the beneficial effects of synbiotic supplementation on immune parameters, which were correlated with synbiotics-induced microbial changes and modified by microbial enterotypes. These findings provided direct evidence supporting the personalized supplementation of synbiotics for immunomodulation.
-
4.
Alterations of gut microbiota are associated with blood pressure: a cross-sectional clinical trial in Northwestern China.
Lv, J, Wang, J, Yu, Y, Zhao, M, Yang, W, Liu, J, Zhao, Y, Yang, Y, Wang, G, Guo, L, et al
Journal of translational medicine. 2023;21(1):429
-
-
-
Free full text
Plain language summary
Hypertension (HTN) is a complex and modifiable risk factor for cardiovascular diseases (CVDs) and stroke, while a diverse range of endogenous and environmental factors contribute to both HTN onset and progression. The adult gut microbiota (GM) consists of trillions of microorganisms and maintains the gut immunity and whole-body homeostasis. The aim of this study was to investigate the GM characteristics in HTN subjects in Northwestern China, and evaluate the associations of GM with blood pressure levels based on sex differences. This study was a cross-sectional study. Participants were randomly selected for the HTN and control groups. A total of 36 HTN subjects (24 females and 12 males) and 18 controls (9 females and 9 males) were randomly selected for metagenomic analysis. Results showed a positive association between GM characteristics and alterations and HTN in both females and males. Thus, GM dysbiosis underlies HTN pathogenesis. Authors conclude that further studies are needed to elucidate the underlying mechanisms and potential therapeutic interventions targeting GM for HTN prevention and management
Abstract
BACKGROUND The human gut microbiota (GM) is involved in the pathogenesis of hypertension (HTN), and could be affected by various factors, including sex and geography. However, available data directly linking GM to HTN based on sex differences are limited. METHODS This study investigated the GM characteristics in HTN subjects in Northwestern China, and evaluate the associations of GM with blood pressure levels based on sex differences. A total of 87 HTN subjects and 45 controls were recruited with demographic and clinical characteristics documented. Fecal samples were collected for 16S rRNA gene sequencing and metagenomic sequencing. RESULTS GM diversity was observed higher in females compared to males, and principal coordinate analysis showed an obvious segregation of females and males. Four predominant phyla of fecal GM included Firmicutes, Bacteroidetes, Actinobacteria and Proteobacteria. LEfSe analysis indicated that phylum unidentified_Bacteria was enriched in HTN females, while Leuconostocaceae, Weissella and Weissella_cibaria were enriched in control females (P < 0.05). Functionally, ROC analysis revealed that Cellular Processes (0.796, 95% CI 0.620 ~ 0.916), Human Diseases (0.773, 95% CI 0.595 ~ 0.900), Signal transduction (0.806, 95% CI 0.631 ~ 0.922) and Two-component system (0.806, 95% CI 0.631 ~ 0.922) could differentiate HTN females as effective functional classifiers, which were also positively correlated with systolic blood pressure levels. CONCLUSIONS This work provides evidence of fecal GM characteristics in HTN females and males in a northwestern Chinese population, further supporting the notion that GM dysbiosis may participate in the pathogenesis of HTN, and the role of sex differences should be considered. Trial registration Chinese Clinical Trial Registry, ChiCTR1800019191. Registered 30 October 2018 - Retrospectively registered, http://www.chictr.org.cn/ .
-
5.
Defecation status, intestinal microbiota, and habitual diet are associated with the fecal bile acid composition: a cross-sectional study in community-dwelling young participants.
Saito, Y, Sagae, T
European journal of nutrition. 2023;62(5):2015-2026
-
-
-
Free full text
-
Plain language summary
Primary bile acids (priBAs) are synthesised from cholesterol in the human liver, conjugated with either taurine or glycine [amino acids], and secreted into the intestinal tract, where they dissolve dietary lipids. Diet is a modifiable factor that can influence defecation status, BAs, and intestinal microbiota. The aim of this study was to identify associations among defecation status, intestinal microbiota, and diet by examining faecal BA composition in community-dwelling young participants. This study was a cross-sectional study which enrolled 70 students. Results showed that 20.9% of the participants had high faecal BA levels with predominantly priBAs. This cluster was associated with an increased relative abundance of Clostridium subcluster XIVa [bacteria], increased frequency of normal faeces, and decreased relative abundance of Bacteroides and Clostridium cluster IV [bacteria]. Conversely, high levels of cytotoxic [toxic to cells] secondary BA (secBA) were associated with low normal defecation frequency, low insoluble fibre intake, and high animal fat intake. Authors concluded that among community-dwelling young adults, secBA production is affected by both dietary and lifestyle related factors. Thus, their findings may inform novel strategies for preventing colorectal cancer and cholelithiasis.
Abstract
PURPOSE Bile acid (BA) metabolism by intestinal bacteria is associated with the risk of gastrointestinal diseases; additionally, its control has become a modern strategy for treating metabolic diseases. This cross-sectional study investigated the influence of defecation status, intestinal microbiota, and habitual diet on fecal BA composition in 67 community-dwelling young participants. METHODS Feces were collected for intestinal microbiota and BA analyses; data about defecation status and dietary habits were collected using the Bristol stool form scales and a brief-type self-administered diet history questionnaire, respectively. The participants were categorized into four clusters based on their fecal BA composition, according to cluster analysis, and tertiles based on deoxycholic acid (DCA) and lithocholic acid (LCA) levels. RESULTS The high primary BA (priBA) cluster with high fecal cholic acid (CA) and chenodeoxycholic acid (CDCA) levels had the highest frequency of normal feces, whereas the second BA (secBA) cluster with high levels of fecal DCA and LCA had the lowest. Alternately, the high-priBA cluster had a distinct intestinal microbiota, with higher Clostridium subcluster XIVa and lower Clostridium cluster IV and Bacteroides. The low-secBA cluster with low fecal DCA and LCA levels had the lowest animal fat intake. Nevertheless, the insoluble fiber intake of the high-priBA cluster was significantly higher than that of the high-secBA cluster. CONCLUSION High fecal CA and CDCA levels were associated with distinct intestinal microbiota. Conversely, high levels of cytotoxic DCA and LCA were associated with increased animal fat intake and decreased frequency of normal feces and insoluble fiber intake. CLINICAL TRIAL REGISTRY University Hospital Medical Information Network (UMIN) Center system (UMIN000045639); date of registration: 15/11/2019.
-
6.
Clinical Trial: Probiotics in Metformin Intolerant Patients with Type 2 Diabetes (ProGasMet).
Nabrdalik, K, Drożdż, K, Kwiendacz, H, Skonieczna-Żydecka, K, Łoniewski, I, Kaczmarczyk, M, Wijata, AM, Nalepa, J, Holleman, F, Nieuwdorp, M, et al
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2023;168:115650
-
-
-
Free full text
Plain language summary
Metformin has been the number one drug of choice for the management of type 2 diabetes, however there is a proportion of individuals who suffer from stomach issues and discontinue therapy. This may be due to the possibility that metformin impacts gut microbiota composition. This randomised control trial of 82 individuals with metformin intolerance aimed to determine the effect of a multi-strain probiotic in conjunction with metformin administration. The results showed that whilst on probiotics, there was a significant improvement in symptoms, with reduced incidence and severity of nausea, reduced frequency and severity of stomach pain and bloating and self-assessed improvement of tolerability of metformin. Nausea was also decreased, but only when the probiotic was allowed time to act. It was concluded that probiotic supplementation improves gastrointestinal side effects associated with metformin intolerance. This study could be used by healthcare professionals to understand that individuals who are on metformin may experience gastrointestinal side effects, which may be relieved with a multi-strain probiotic.
Abstract
BACKGROUND For decades, metformin has been the drug of first choice in the management of type 2 diabetes. However, approximately 2-13% of patients do not tolerate metformin due to gastrointestinal (GI) side effects. Since metformin influences the gut microbiota, we hypothesized that a multi-strain probiotics supplementation would mitigate the gastrointestinal symptoms associated with metformin usage. METHODS AND ANALYSIS This randomized, double-blind, placebo-controlled, single-center, cross-over trial (ProGasMet study) assessed the efficacy of a multi-strain probiotic in 37 patients with metformin intolerance. Patients were randomly allocated (1:1) to receive probiotic (PRO-PLA) or placebo (PLA-PRO) at baseline and, after 12 weeks (period 1), they crossed-over to the other treatment arm (period 2). The primary outcome was the reduction of GI adverse events of metformin. RESULTS 37 out of 82 eligible patients were enrolled in the final analysis of whom 35 completed the 32 weeks study period and 2 patients resigned at visit 5. Regardless of the treatment arm allocation, while on probiotic supplementation, there was a significant reduction of incidence (for the probiotic period in PRO-PLA/PLA-PRO: P = 0.017/P = 0.054), quantity and severity of nausea (P = 0.016/P = 0.024), frequency (P = 0.009/P = 0.015) and severity (P = 0.019/P = 0.005) of abdominal bloating/pain as well as significant improvement in self-assessed tolerability of metformin (P < 0.01/P = 0.005). Moreover, there was significant reduction of incidence of diarrhea while on probiotic supplementation in PRO-PLA treatment arm (P = 0.036). CONCLUSION A multi-strain probiotic diminishes the incidence of gastrointestinal adverse effects in patients with type 2 diabetes and metformin intolerance.
-
7.
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
-
-
-
-
Free full text
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:
-
X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
-
B: Systematic reviews including RCTs of limited number
-
C: Non-randomized trials, observational studies, narrative reviews
-
D: Case-reports, evidence-based clinical findings
-
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.
-
8.
Lactulose regulates gut microbiota dysbiosis and promotes short-chain fatty acids production in acute pancreatitis patients with intestinal dysfunction.
Wang, J, Jiang, M, Hu, Y, Lei, Y, Zhu, Y, Xiong, H, He, C
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2023;163:114769
-
-
-
Free full text
Plain language summary
Acute pancreatitis (AP) is commonly associated with gastrointestinal (GI) dysfunction in the early phase which in turn increases the risk of infectious complications and as such poorer prognosis. Lactulose is a prebiotic that can modulate the gut microbiota and intestinal metabolites. The aim of this open-label, randomised controlled study, involving 83 patients with moderate-severe AP and associated GI dysfunction, was to evaluate the efficacy of lactulose on intestinal function, infectious complications and prognosis compared to rhubarb, which has shown benefits for the aforementioned outcomes of AP. GI function improved significantly within 7 days in both groups, with no difference between groups. Whilst one marker (D-lac) of intestinal permeability was improved in both groups after 7 days, another marker (DAO) showed no improvement in either group. There was no significant difference between groups in this respect. There was no difference in clinical outcomes between groups, but certain inflammatory markers (TNF-a, IL-6) declined more in the lactulose than in the rhubarb group. More beneficial changes in the microbiota and its metabolites were seen in the lactulose, compared to the rhubarb group. The authors concluded that lactulose is a potent alternative to rhubarb for patients with AP and associated GI dysfunction.
Abstract
BACKGROUND Intestinal dysfunction is one of the common complications in the early stage of acute pancreatitis (AP), which often associates with bad outcome. Lactulose, as a prebiotic, has been widely used to improve gut health, yet its effect on AP is unclear. METHODS This was a prospective, randomized trial of moderate severe AP patients complicated with intestinal dysfunction. A total of 73 participants were randomly assigned to receive either lactulose or Chinese herb rhubarb for 1 week. The primary efficacy endpoint was the recovery of intestinal function. The serum levels of inflammatory cytokines and gut barrier indexes were examined. The fecal samples from patients before and after treatment were collected. 16 S rRNA gene sequencing analysis was performed to explore the composition of gut microbiota and the amount of short-chain fatty acids (SCFAs) were detected by gas chromatography-mass spectrometry (GC-MS). RESULTS The intestinal dysfunction was prominently improved after 7 days of treatment with either lactulose or rhubarb. The serum levels of cytokines and gut permeability index were decreased after treatment, with stronger down-regulated degree in lactulose group than rhubarb. The potential beneficial genus Bifidobacterium was enriched in lactulose group, while pathogenic bacteria including Escherichia-Shigella and Neisseria were abundant in rhubarb group. Of note, the level of SCFAs was remarkably increased after treatment, with higher amount in lactulose group than rhubarb group. CONCLUSIONS Lactulose could not only restore intestinal function but also regulate gut microbiota and promote the production of SCFAs.
-
9.
Safety and Tolerability of SER-109 as an Investigational Microbiome Therapeutic in Adults With Recurrent Clostridioides difficile Infection: A Phase 3, Open-Label, Single-Arm Trial.
Sims, MD, Khanna, S, Feuerstadt, P, Louie, TJ, Kelly, CR, Huang, ES, Hohmann, EL, Wang, EEL, Oneto, C, Cohen, SH, et al
JAMA network open. 2023;6(2):e2255758
-
-
-
Free full text
-
Plain language summary
Clostridioides difficile infection (CDI) is most commonly caused by treatment with broad-spectrum antibiotics. Antibiotic treatment of CDI is generally successful but recurrences of CDI occur in 15-25% of patients after the first episode, and up to 40% of patients with a previous recurrence. This is thought to be due to persistent microbiome disruption, including a depletion of Firmicutes bacteria. The aim of this single-arm, open-label trial was to evaluate the safety and effectiveness of an investigational, microbiome therapeutic composed of purified Firmicutes spores (SER-109) to prevent CDI recurrences. 263 patients were enrolled in the study and received SER-109 on 3 consecutive days, started within 4 days of completion of antibiotic treatment for CDI recurrence. Follow-up was 24 weeks. Most patients were aged 65 years or older and had a high prevalence of comorbidities. There were no reports of serious adverse events which were considered related to SER-109. By week 24, 36 patients (13.7%) had experienced a CDI recurrence. This was independent of demographics, type of antibiotic treatment and number of prior recurrences. The authors concluded that the data suggest a role of SER-109 in the management of recurrent CDI.
Abstract
IMPORTANCE A safe and effective treatment for recurrent Clostridioides difficile infection (CDI) is urgently needed. Antibiotics kill toxin-producing bacteria but do not repair the disrupted microbiome, which promotes spore germination and infection recurrence. OBJECTIVES To evaluate the safety and rate of CDI recurrence after administration of investigational microbiome therapeutic SER-109 through 24 weeks. DESIGN, SETTING, AND PARTICIPANTS This phase 3, single-arm, open-label trial (ECOSPOR IV) was conducted at 72 US and Canadian outpatient sites from October 2017 to April 2022. Adults aged 18 years or older with recurrent CDI were enrolled in 2 cohorts: (1) rollover patients from the ECOSPOR III trial who had CDI recurrence diagnosed by toxin enzyme immunoassay (EIA) and (2) patients with at least 1 CDI recurrence (diagnosed by polymerase chain reaction [PCR] or toxin EIA), inclusive of their acute infection at study entry. INTERVENTIONS SER-109 given orally as 4 capsules daily for 3 days following symptom resolution after antibiotic treatment for CDI. MAIN OUTCOMES AND MEASURES The main outcomes were safety, measured as the rate of treatment-emergent adverse events (TEAEs) in all patients receiving any amount of SER-109, and cumulative rates of recurrent CDI (toxin-positive diarrhea requiring treatment) through week 24 in the intent-to-treat population. RESULTS Of 351 patients screened, 263 were enrolled (180 [68.4%] female; mean [SD] age, 64.0 [15.7] years); 29 were in cohort 1 and 234 in cohort 2. Seventy-seven patients (29.3%) were enrolled with their first CDI recurrence. Overall, 141 patients (53.6%) had TEAEs, which were mostly mild to moderate and gastrointestinal. There were 8 deaths (3.0%) and 33 patients (12.5%) with serious TEAEs; none were considered treatment related by the investigators. Overall, 23 patients (8.7%; 95% CI, 5.6%-12.8%) had recurrent CDI at week 8 (4 of 29 [13.8%; 95% CI, 3.9%-31.7%] in cohort 1 and 19 of 234 [8.1%; 95% CI, 5.0%-12.4%] in cohort 2), and recurrent CDI rates remained low through 24 weeks (36 patients [13.7%; 95% CI, 9.8%-18.4%]). At week 8, recurrent CDI rates in patients with a first recurrence were similarly low (5 of 77 [6.5%; 95% CI, 2.1%-14.5%]) as in patients with 2 or more recurrences (18 of 186 [9.7%; 95% CI, 5.8%-14.9%]). Analyses by select baseline characteristics showed consistently low recurrent CDI rates in patients younger than 65 years vs 65 years or older (5 of 126 [4.0%; 95% CI, 1.3%-9.0%] vs 18 of 137 [13.1%; 95% CI, 8.0%-20.0%]) and patients enrolled based on positive PCR results (3 of 69 [4.3%; 95% CI, 0.9%-12.2%]) vs those with positive toxin EIA results (20 of 192 [10.4%; 95% CI, 6.5%-15.6%]). CONCLUSIONS AND RELEVANCE In this trial, oral SER-109 was well tolerated in a patient population with recurrent CDI and prevalent comorbidities. The rate of recurrent CDI was low regardless of the number of prior recurrences, demographics, or diagnostic approach, supporting the beneficial impact of SER-109 for patients with CDI. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT03183141.
-
10.
Gut microbiota modulate distal symmetric polyneuropathy in patients with diabetes.
Yang, J, Yang, X, Wu, G, Huang, F, Shi, X, Wei, W, Zhang, Y, Zhang, H, Cheng, L, Yu, L, et al
Cell metabolism. 2023;35(9):1548-1562.e7
-
-
-
Free full text
Plain language summary
Distal symmetric polyneuropathy (DSPN) is the most common complication associated with diabetes, which can lead to pain, numbness, and weakness or tingling in the limbs or parts of the body. There are no cures for DSPN only drugs to manage symptoms, highlighting a need for further research. Recently it has been shown that the gut microbiota of individuals with DSPN differs to that of healthy individuals, but it is unclear as to the significance of this. This randomised control trial aimed to determine the effect of transplanting faecal microbiota from healthy individuals into those with DSPN. The results showed that DSPN was associated with a decreased abundance of beneficial gut bacteria and an increased abundance of pathogenic bacteria. Furthermore, compared to placebo, DSPN was alleviated in all 22 patients who received a faecal microbiota transplant from healthy subjects. There was an increase in gut microbiota associated with the production of beneficial short chain fatty acids and a decrease in toxin production. It was concluded that dysbiosis in the gut microbiota contributes to DSPN, which can be alleviated by faecal microbial transplant from healthy individuals. This study could be used by healthcare professionals to understand that the gut microbiota has an important role in DSPN. Further larger studies would be warranted before recommending faecal microbial transplant to individuals with this disorder.
Abstract
The pathogenic mechanisms underlying distal symmetric polyneuropathy (DSPN), a common neuropathy in patients with diabetes mellitus (DM), are not fully understood. Here, we discover that the gut microbiota from patients with DSPN can induce a phenotype exhibiting more severe peripheral neuropathy in db/db mice. In a randomized, double-blind, and placebo-controlled trial (ChiCTR1800017257), compared to 10 patients who received placebo, DSPN was significantly alleviated in the 22 patients who received fecal microbiota transplants from healthy donors, independent of glycemic control. The gut bacterial genomes that correlated with the Toronto Clinical Scoring System (TCSS) score were organized in two competing guilds. Increased guild 1, which had higher capacity in butyrate production, and decreased guild 2, which harbored more genes in synthetic pathway of endotoxin, were associated with improved gut barrier integrity and decreased proinflammatory cytokine levels. Moreover, matched enterotype between transplants and recipients showed better therapeutic efficacy with more enriched guild 1 and suppressed guild 2. Thus, changes in these two competing guilds may play a causative role in DSPN and have the potential for therapeutic targeting.