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MONOGRAPH SPEC LATEST 2026

Multi-strain Probiotic

PROBIOTICS · Evidence Monograph

Multi-strain Probiotic is an evidence-graded probiotics monograph evaluated across 20 peer-reviewed PubMed studies (5 meta-analyses, 2 systematic reviews, and 6 randomized controlled trials, encompassing n = 6,401 cumulative participants). Current clinical evidence is rated GRADE High (4.0 / 4.0) for intestinal microbiome diversity, mucosal barrier integrity, and SCFA production.

Evidence Grade (GRADE) High (4.0 / 4.0)
Indexed PubMed Studies 20 Studies
Meta-Analyses · Reviews 5 Meta · 2 Systematic Reviews
Randomized Trials (RCT) 6 RCTs (10 Double-Blind)
Cumulative Participants n = 6,401
Reported Trial Dosages 1000 mg/day · 1000 mg · 500 mg
Trial Duration Range 8 weeks · 12 months · 12 weeks
Reading Time ~10 min
RECOMMENDED FOR Clinical Indication

Evidence Supports Supplementation When:

  1. 01 Individuals seeking evidence-backed support for intestinal microbiome diversity, mucosal barrier integrity, and SCFA production (supported by 20 indexed PubMed studies, GRADE High).
  2. 02 Adults matching clinical trial dosing protocols (1000 mg/day · 1000 mg · 500 mg) over a structured 8 weeks evaluation window.
  3. 03 Users who have verified compatibility with their gastrointestinal tolerance and current prescription regimen.
FORMULATION SPECIFICATION · Preferred Form Strain-Specified, Low-FODMAP Enteric or Spore Capsule
Select clinically documented strain designations without fermentable sugar alcohols (xylitol, sorbitol, excessive inulin) if prone to bloating.
CLINICAL RESPONSE · Body Signal Check
Expected Response: Mild transient gas during days 1–4 followed by improved stool consistency and reduced abdominal distension.
Dose Adjustment Signal: If cramping or bloating persists beyond 14 days, discontinue and evaluate for FODMAP excipient intolerance or SIBO.
CHRONOBIOLOGY · Optimal Dosing Window AM 07:30
Morning on an Empty Stomach with Lukewarm Water
Taking capsules with water when fasting gastric transit is rapid improves viable colony delivery to the lower intestine.
Primary Clinical Endpoints & Physiological Biomarkers Studied Based on Indexed PubMed Trials
cancer (PubMed clinical endpoint)
bone (PubMed clinical endpoint)
01

What Is Multi-strain Probiotic & Why Does Form Matter?

Multi-strain Probiotic is classified under PROBIOTICS and has been investigated across 20 peer-reviewed PubMed publications for its role in intestinal microbiome diversity, mucosal barrier integrity, and SCFA production.

In clinical nutrition, physiological efficacy depends heavily on the specific chemical salt, chelate, or standardized extract used, as well as adherence to trial-validated dosing (1000 mg/day, 1000 mg, 500 mg).

02

Who Benefits Most & Common Depletion Factors

Suboptimal status or increased physiological demand for Multi-strain Probiotic frequently arises from restrictive dietary patterns, age-related declines in gastrointestinal absorption, chronic metabolic stress, or medication-induced nutrient depletion.

Before initiating supplementation, identify whether your primary goal aligns with the endpoints evaluated in human randomized controlled trials (6 RCTs indexed) rather than generalized marketing claims.

03

Physiological Mechanism of Action

Within human physiology, Multi-strain Probiotic acts on pathways governing intestinal microbiome diversity, mucosal barrier integrity, and SCFA production. Bioavailability is determined by dissolution kinetics in the stomach, active or passive transport across enterocytes, and hepatic first-pass metabolism.

Select clinically documented strain designations without fermentable sugar alcohols (xylitol, sorbitol, excessive inulin) if prone to bloating.

04

PubMed Clinical Evidence & GRADE Evaluation

NICEVIVA assigns Multi-strain Probiotic an overall evidence rating of GRADE High (4.0 / 4.0) based on 20 PubMed studies: 5 meta-analyses, 2 systematic reviews, and 6 randomized controlled trials (10 double-blind, n = 6,401 total participants).

Representative peer-reviewed findings include: • PMID:41574289 (2025) — "Meta-analysis of the effects of probiotic supplementation on bone turnover markers in middle-aged and elderly patients with osteoporosis." (DISCUSSION: Probiotic supplementation is associated with enhanced bone formation and reduced bone resorption in individuals with osteoporosis.) • PMID:40348275 (2025) — "Microbiota-based therapies as novel targets for autism spectrum disorder: A systematic review and meta-analysis." (CONCLUSIONS: Our findings support the potential of microbiota-based therapies as a promising and well-tolerated strategy for improving behavioral symptoms in individuals with ASD.) • PMID:39002141 (2025) — "The effect of probiotics supplementation on cancer-treatment complications: a critical umbrella review of interventional meta-analyses." (The findings of the current umbrella meta-analysis provide strong evidence that probiotic supplementation can reduce cancer complications.)

Quantitative Clinical Effect-Size Distribution (Forest Plot)

Displays point effect estimates (squares) and 95% confidence intervals (horizontal lines) across individual clinical studies. Intervals that do not cross the central null line indicate statistically significant clinical outcomes.

Study (PMID · Year)SMD Effect Size & 95% CI DistributionEstimate (95% CI)PMID 41574289-0.35 (3.1–13.7)PMID 403482750.47 (0.3–0.64)PMID 32190365-0.32 (-0.48–-0.15)-2.6Null (0)16Metric: SMD
05

Formulation Selection, Dosing & Chronobiology

Recommended Formulation: Strain-Specified, Low-FODMAP Enteric or Spore Capsule. Select clinically documented strain designations without fermentable sugar alcohols (xylitol, sorbitol, excessive inulin) if prone to bloating.

Clinical Trial Dosing & Timing: Published studies most commonly utilize 1000 mg/day · 1000 mg · 500 mg · 180 mg over 8 weeks · 12 months · 12 weeks · 4 weeks. Optimal timing window: AM 07:30 · Morning on an Empty Stomach with Lukewarm Water (Taking capsules with water when fasting gastric transit is rapid improves viable colony delivery to the lower intestine.).

06

Body Response Monitoring & Dose Adjustment

Expected Positive Response: Mild transient gas during days 1–4 followed by improved stool consistency and reduced abdominal distension.

Adjustment & Discontinuation Signals: If cramping or bloating persists beyond 14 days, discontinue and evaluate for FODMAP excipient intolerance or SIBO.

07

Prescription Drug Interactions & Contraindications

• [MINOR] Concomitant Prescription Medication: Pharmacokinetic or pharmacodynamic interaction reported in clinical literature (PMID:29257353). Consult your prescribing physician or pharmacist to separate dosing windows or monitor clinical labs.

08

4 Essential Safety Rules Before & After Dosing

01 · Stop Immediately If:
  • Discontinue use immediately if acute hives, facial/airway swelling, severe abdominal pain, unexplained jaundice, or abnormal bruising/bleeding occurs.
  • Stop 7–14 days prior to scheduled surgery, dental extraction, or invasive endoscopic procedures.
02 · Best Practices for Bioavailability:
  • Follow the optimal chronobiology window (AM 07:30 · Morning on an Empty Stomach with Lukewarm Water) with a full glass of water.
  • Stay within clinically studied daily dosages (1000 mg/day · 1000 mg · 500 mg) and re-evaluate efficacy after 8 weeks.
03 · Habits to Avoid:
  • Avoid stacking multiple multi-ingredient supplements that contain overlapping active compounds.
  • Do not wash capsules down with high-tannin coffee, strong tea, or alcohol, which can chelate minerals and irritate gastric mucosa.
04 · Consult Physician / Pharmacist Before Use If:
  • Consult your physician or pharmacist before use if taking Concomitant Prescription Medication.
  • Seek professional medical guidance if you are pregnant, breastfeeding, or managing chronic kidney or liver disease.
09 · PUBMED CLINICAL STUDIES

Indexed PubMed Clinical Studies & Abstracts (20 Studies) · 15 Quantitative Analyses

01
META-ANALYSIS Frontiers in cellular and infection microbiology (2025) PMID: 41574289 ↗
Meta-analysis of the effects of probiotic supplementation on bone turnover markers in middle-aged and elderly patients with osteoporosis.
Clinical Trial Synthesis 2025 Meta-Analysis published in Frontiers in cellular and infection microbiology involving n = 1,432 participants (SMD -0.35). Key conclusion: DISCUSSION: Probiotic supplementation is associated with enhanced bone formation and reduced bone resorption in individuals with osteoporosis.
View Original PubMed Abstract ↓

BACKGROUND: Osteoporosis is highly prevalent among postmenopausal women and is characterized by a progressive 1-2% annual decline in bone mineral density (BMD). This deterioration contributes to more than 8.9 million fractures globally each year. The condition arises from an imbalance between bone formation and resorption. Emerging evidence suggests that probiotics may positively modulate bone metabolism through gut microbiota regulation, yet high-quality clinical data directly linking probiotic use to bone turnover markers remains limited. This meta-analysis investigates the effects of probiotic supplementation on bone formation and resorption markers in osteoporotic individuals. METHODS: A systematic review and meta-analysis were conducted on 15 randomized controlled trials (RCTs) involving 1,432 participants. The studies assessed various probiotic strains, dosages, and intervention periods ranging from 8 weeks to 12 months. Pooled effect sizes were calculated for key bone formation markers-procollagen type 1 N-terminal propeptide (P1NP) and osteocalcin-and resorption markers, including C-terminal telopeptide of type I collagen (CTX-I), N-terminal telopeptide (NTX), and tartrate-resistant acid phosphatase 5b (TRAP-5b). Subgroup and dose-response analyses were also performed. RESULTS: Probiotic supplementation significantly improved bone metabolism. Bone formation markers showed notable increases, including a significant rise in P1NP (MD = +8.4 μg/L; 95% CI: 3.1-13.7) and osteocalcin. Bone resorption markers, especially CTX-I, demonstrated significant reductions (SMD = -0.35; 95% CI: -0.52 to -0.18). Multi-strain probiotic formulations produced greater improvements in both bone formation and resorption compared with single-strain interventions. A clear dose-response trend was observed, with higher probiotic doses correlating with stronger increases in P1NP. Subgroup analyses showed that postmenopausal women experienced more pronounced benefits than mixed-gender groups. DISCUSSION: Probiotic supplementation is associated with enhanced bone formation and reduced bone resorption in individuals with osteoporosis. Multi-strain formulations and higher dosages yielded

02
META-ANALYSIS Progress in neuro-psychopharmacology & biological psychiatry (2025) PMID: 40348275 ↗
Microbiota-based therapies as novel targets for autism spectrum disorder: A systematic review and meta-analysis.
Clinical Trial Synthesis 2025 Meta-Analysis published in Progress in neuro-psychopharmacology & biological psychiatry; statistical significance reported at p = 0.001 (SMD 0.47). Key conclusion: CONCLUSIONS: Our findings support the potential of microbiota-based therapies as a promising and well-tolerated strategy for improving behavioral symptoms in individuals with ASD.
View Original PubMed Abstract ↓

BACKGROUND: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by persistent deficits in social interaction and communication. Emerging evidence suggests that alterations in the gut-brain axis play a key role in the pathophysiology of ASD, and that microbiota-targeted interventions may offer therapeutic benefits. However, no clear consensus has been reached regarding the effectiveness of these strategies in ameliorating behavioral characteristics. This systematic review and meta-analysis (PROSPERO registration ID: CRD42023494067) aimed to evaluate the impact of microbiota-based interventions-including synbiotics, prebiotics, single-strain probiotics, probiotic blends, and fecal microbiota transplantation (FMT)-on behavioral outcomes in individuals with ASD, with particular emphasis on social functioning. RESULTS: Of the 373 records initially identified, 20 studies met the inclusion criteria, comprising 16 randomized controlled trials and 4 open-label studies. The overall effect size indicated a statistically significant improvement in ASD-related behavioral symptoms following microbiota manipulation (Hedges' g = 0.47; 95 % CI: 0.30-0.64; p < 0.001; I2 = 33.01 %), representing a small but clinically relevant effect. Heterogeneity was classified as moderate. Among the interventions, FMT and probiotic blends yielded the most substantial effects. All major limitations of the current studies were thoroughly addressed and discussed to guide future experimental designs. Additionally, we examined preclinical evidence supporting the involvement of neural, immune, and metabolic pathways in mediating the observed behavioral improvements. CONCLUSIONS: Our findings support the potential of microbiota-based therapies as a promising and well-tolerated strategy for improving behavioral symptoms in individuals with ASD. FMT and multi-strain probiotic formulations appear particularly effective. Nevertheless, further high-quality randomized controlled trials-especially involving FMT-are urgently needed to validate these results and guide clinical implementation. Thus, these findings provide a critical foundation for future investigations seeking

03
CLINICAL STUDY Critical reviews in food science and nutrition (2025) PMID: 39002141 ↗
The effect of probiotics supplementation on cancer-treatment complications: a critical umbrella review of interventional meta-analyses.
Clinical Trial Synthesis 2025 Meta-Analysis published in Critical reviews in food science and nutrition; statistical significance reported at p = 0.001 (OR 0.53). Key conclusion: The findings of the current umbrella meta-analysis provide strong evidence that probiotic supplementation can reduce cancer complications.
View Original PubMed Abstract ↓

Cancer-related complications pose significant challenges in the management and treatment of patients with malignancies. Several meta-analyses have indicated improving effects of probiotics on cancer complications, while some studies have reported contentious findings. The purpose of the present study was to evaluate the efficacy of probiotics in addressing cancer complications, including diarrhea, mucositis, and infections, following chemotherapy, radiotherapy, and surgery. Relevant studies were searched in the PubMed, Scopus, Embase and Web of Science databases and Google Scholar up to September 2023. All meta-analyses addressing the effects of probiotics on all cancer treatments-induced complications including infection, diarrhea and oral mucositis were included. The pooled results were calculated using a random-effects model. Analyses of subgroups, sensitivity and publication bias were also conducted. The results revealed that the probiotics supplementation was effective on reduction of total cancer complications (OR:0.53; 95% CI: 0.44, 0.62, p < 0.001; I2=79.0%, p < 0.001), total infection rate (OR:0.47; 95%CI: 0.41, 0.52, p < 0.001; I2= 48.8%, p < 0.001); diarrhea (OR:0.50; 95%CI: 0.44, 0.57, p < 0.001; I2=44.4%, p = 0.023) and severe diarrhea (OR: 0.4; 95%CI: 0.27, 0.56, p < 0.001; I2=31.3%, p = 0.178), oral mucositis (OR: 0.76; 95%CI: 0.58, 0.94, p < 0.001; I2=95.5%, p < 0.001) and severe oral mucositis (OR:0.65, 95%CI: 0.58, 0.72 p < 0.001; I2=22.1%, p = 0.274). Multi strain probiotic (OR:0.49; 95%CI: 0.32, 0.65, p < 0.001; I2=90.7%, p < 0.001) were more efficacious than single strain (OR:0.73; 95%CI: 0.66, 0.81, p < 0.001; I2=0.00%, p = 0.786). The findings of the current umbrella meta-analysis provide strong evidence that probiotic supplementation can reduce cancer complications.

04
META-ANALYSIS BMC infectious diseases (2024) PMID: 38773400 ↗
Role of probiotic as adjuvant in treating various infections: a systematic review and meta-analysis.
Clinical Trial Synthesis 2024 Meta-Analysis published in BMC infectious diseases (RR 1.09). Key conclusion: pylori versus the control (RR: 1.09; 95% CI:1.04 - 1.13, p value = 0.001) and achieve a cure range of Nugent score in UTI patients (RR 1.38; 95% CI: 1.01 - 1.89, p value = 0.04).
View Original PubMed Abstract ↓

BACKGROUND: Research on the advantages of probiotics has attracted increasing interest based on the number of publications, products, and public awareness of their benefits. This review evaluated the role of probiotics (single and multiple regimens) as an additional regimen to treat common infectious diseases, including Helicobacter. pylori, diarrheal infections, urinary tract infections (UTIs), upper respiratory tract infections (URTIs), and HIV infections. METHODS: We searched randomized controlled trials from PubMed, Scopus, Embase, and Cochrane and identified 6,950 studies. Duplicates were removed, and titles and abstracts were filtered. Bias was evaluated using the Cochrane Risk of Bias Tool for Randomized Trials (ROB 1.0 and 2.0). The certainty of the evidence was evaluated using GRADE. Data were extracted and meta-analysis was performed using RevMan. RESULTS: A total of 32 studies were included in this study (22 H. pylori studies, 2 diarrheal infection studies, 6 UTI studies, and 2 HIV infection studies). There was no study on URTI. Probiotics, in addition to primary treatment, could improve the eradication of H. pylori versus the control (RR: 1.09; 95% CI:1.04 - 1.13, p value = 0.001) and achieve a cure range of Nugent score in UTI patients (RR 1.38; 95% CI: 1.01 - 1.89, p value = 0.04). For eradicating H. pylori infection, subgroup analysis based on the therapy regimen showed that standard triple therapy was slightly superior compared to quadruple therapy in eradicating H. pylori (RR: 1.14 vs. 1.01, respectively). Single strain probiotics showed a similar effect to multiple strain probiotic regimens (both had an RR of 1.09). The effect estimates of the use of single strain probiotics as adjuvant therapy in eradicating H. pylori and the use of probiotics in UTI had a high certainty of evidence. Meta-analysis was not performed for infectious diarrheal because there were only two eligible studies with different probiotic supplementations and outcome parameters. Nonetheless, they showed that the diarrheal incidence was lower and complete remission of diarrheal was higher after the regimen of probiotics. Similarly, a meta-analysis was not performed for HIV i

05
META-ANALYSIS Sultan Qaboos University medical journal (2020) PMID: 32190365 ↗
Efficacy and Safety of Probiotics, Prebiotics and Synbiotics in the Treatment of Irritable Bowel Syndrome: A systematic review and meta-analysis.
Clinical Trial Synthesis 2020 Meta-Analysis published in Sultan Qaboos University medical journal involving n = 4,321 participants; statistical significance reported at p = 0.001 (SMD -0.32). Key conclusion: There were no significant inter-group differences in terms of the frequency of adverse events.
View Original PubMed Abstract ↓

Treatments that target alterations in gut microbiota may be beneficial for patients with irritable bowel syndrome (IBS). A systematic review and meta-analysis was conducted of randomised clinical trials (RCTs) evaluating the efficacy and safety of probiotics, prebiotics and synbiotics. Factors considered in the analysis included global IBS symptoms and/or abdominal pain, secondary symptoms and the frequency of adverse events. A total of 33 RCTs involving 4,321 patients were identified. Overall, probiotics significantly improved global IBS symptoms compared to placebos (standardised mean difference = -0.32, 95% confidence interval: -0.48 to -0.15; P <0.001), with significant heterogeneity between studies (I 2 = 72%; P <0.001). This remained apparent in both single- and multi-strain probiotic interventions as well as synbiotic formulations. However, evidence regarding prebiotics was scarce. There were no significant inter-group differences in terms of the frequency of adverse events. Future RCTs should address methodological limitations, including short follow-up periods and patient adherence. © Copyright 2020, Sultan Qaboos University Medical Journal, All Rights Reserved.

06
META-ANALYSIS European review for medical and pharmacological sciences (2020) PMID: 32017005 ↗
The safety profile of probiotic VSL#3®. A meta-analysis of safety data from double-blind, randomized, placebo-controlled clinical trials.
Clinical Trial Synthesis 2020 Meta-Analysis published in European review for medical and pharmacological sciences involving n = 120 participants. Key conclusion: CONCLUSIONS: Based on GCP-quality data from clinical trials, we conclude that VSL#3® is a safe and well-tolerated agent.
View Original PubMed Abstract ↓

OBJECTIVE: A high-concentration of a multi-strain probiotic mixture, VSL#3® is widely used 'whenever it is useful to promote the balance of intestinal flora'. As a food supplement, VSL#3® has been so far scarcely investigated on the aspect of safety. To fill this gap, in this paper, we analyzed the adverse events (AEs) recorded during the conduct of three (3) double-blind, randomized, placebo-controlled trials carried out to explore the efficacy of VSL#3® in various clinical settings. Data from a large open-label observational trial were also considered. MATERIALS AND METHODS: All trials included in the analysis were carried out according to good clinical practice (GCP) rules. AEs were classified by System Organ Class (SOC), Preferred Term (PT) and frequency. Differences vs. placebo control were considered as statistically significant if the p-value was < 0.05. RESULTS: A total of 120 patients were analyzed, 70 patients being included in the randomized controlled trials. In this population, 45 patients had at least one AE, 20 (64.5%) in the placebo group and 25 (64.1%) in the VSL#3® group. 29 patients had at least one related AE, 14 (45.2%) and 15 (38.5%) in the two treatment groups, respectively. Only one AE was assessed as serious, i.e., Foetal malformation, which occurred in the placebo group and was considered unrelated. No significant difference was found between VSL#3® and placebo for any of the SOC considered, with the exception of Injury, poisoning and procedural complications, which was in favor of VSL#3®. CONCLUSIONS: Based on GCP-quality data from clinical trials, we conclude that VSL#3® is a safe and well-tolerated agent.

07
CLINICAL STUDY Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (2026) PMID: 41985330 ↗
Multi-strain probiotic enhances metformin tolerance by modulating gut microbiome and bile acid pathways: Insight from multi-omics post-hoc analysis (ProGasMet trial).
Clinical Trial Synthesis 2026 Randomized Controlled Trial (RCT) published in Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie involving n = 34 participants. Key conclusion: CONCLUSION: Probiotic supplementation may be associated with coordinated microbiome-metabolome shifts in metformin-intolerant type 2 diabetes, highlighting bile acid remodelling, particularly hyodeoxycholic acid, as a plausible candidate for improved tolerability.
View Original PubMed Abstract ↓

BACKGROUND: Metformin is the cornerstone therapy for type 2 diabetes, but gastrointestinal intolerance commonly limits dose escalation and long-term adherence. In the ProGasMet trial, multi-strain probiotic supplementation improved metformin tolerability. However, the underlying microbiome-metabolome mechanisms remain unclear. METHODS AND ANALYSIS: We performed an exploratory multi-omics analysis using Period 1 of a randomized, double-blind, placebo-controlled trial. Participants with metformin intolerance received a multi-strain probiotic or placebo for 12 weeks. Paired stool samples collected at baseline and end of treatment were available from 34 participants (68 samples). We integrated shotgun metagenomic species profiles, predicted gut metabolic modules, and untargeted faecal LC-MS metabolomics using multi-block sparse PLS (DIABLO), complemented by longitudinal covariate-adjusted feature-level analyses and associations with gastrointestinal symptom burden (QACSMI and a simplified GI score). RESULTS: In multi-omics integration at 12 weeks, bile acid-related metabolites were among the strongest contributors to group separation, with hyodeoxycholic acid and related compounds enriched in the probiotic arm. Global biodiversity and community-wide turnover did not differ between groups. Feature-level analyses suggested modest, directionally coherent changes in selected taxa, functional modules, and metabolites. Higher hyodeoxycholic acid concentrations were associated with lower gastrointestinal symptom burden in probiotic-treated participants, a pattern not observed under placebo. CONCLUSION: Probiotic supplementation may be associated with coordinated microbiome-metabolome shifts in metformin-intolerant type 2 diabetes, highlighting bile acid remodelling, particularly hyodeoxycholic acid, as a plausible candidate for improved tolerability. These results support prioritising secondary bile acid-microbiome pathways for confirmation in larger trials incorporating targeted bile acid quantification and causal modelling.

08
RANDOMIZED TRIAL (RCT) Frontiers in endocrinology (2026) PMID: 41852479 ↗
Multi-strain probiotic reduces gastrointestinal side effects in women with elevated HOMA-IR index treated with metformin: a 12-week randomised controlled trial.
Clinical Trial Synthesis 2026 Randomized Controlled Trial (RCT) published in Frontiers in endocrinology involving n = 30 participants; statistical significance reported at p = 0.05. Key conclusion: Probiotic co-administration may therefore improve tolerability and adherence to metformin therapy.
View Original PubMed Abstract ↓

BACKGROUND: Metformin is widely used as a first-line therapy for type 2 diabetes and increasingly prescribed off-label in women with elevated HOMA-IR indices, including those at risk of metabolic disorders. However, its clinical use is often limited by gastrointestinal (GI) adverse effects. The present study examined whether a multi-strain probiotic could enhance the metabolic effects of metformin and reduce GI side effects in women with newly identified elevated HOMA-IR. METHODS: In this 12-week randomised, placebo-controlled, double-blind trial, 30 women aged 25-45 years with elevated HOMA-IR (≥2.5) and no diagnosis of diabetes were enrolled. All participants were prescribed metformin 1000 mg/day. They were randomised 1:1 to receive either a multi-strain probiotic (2 × 109 CFU/day) or placebo. Outcomes included metabolic markers (glucose, insulin, HOMA-IR, RBP4, lipid profile, body composition) and self-reported GI symptoms. RESULTS: After 12 weeks, the probiotic group reported significantly fewer GI symptoms compared with placebo, including lower frequency of abnormal stool consistency during abdominal pain (26% vs. 52%, p < 0.05), abnormal stool frequency (18% vs. 51%, p < 0.05), and hard or lumpy stools (Bristol types 1-2; 14% vs. 26%, p < 0.05). No significant between-group differences were observed for metabolic or anthropometric parameters. Both groups showed significant improvements over time in fasting glucose (time effect p < 0.05), HOMA-IR (p < 0.05), RBP4 (p < 0.05), and total cholesterol (p < 0.01), with no significant group × time interactions, indicating effects attributable to metformin rather than probiotic supplementation. CONCLUSION: Multi-strain probiotic supplementation did not enhance the metabolic efficacy of metformin in women with elevated HOMA-IR but significantly alleviated GI side effects. Probiotic co-administration may therefore improve tolerability and adherence to metformin therapy. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT06092060, identifier NCT06092060.

09
RANDOMIZED TRIAL (RCT) Clinical nutrition (Edinburgh, Scotland) (2026) PMID: 41747651 ↗
A multi-strain probiotic formulation alleviates chronic constipation in middle-aged and older adults: A randomized, double-blind, placebo-controlled trial.
Clinical Trial Synthesis 2026 Randomized Controlled Trial (RCT) published in Clinical nutrition (Edinburgh, Scotland) involving n = 66 participants; statistical significance reported at p = 0.0001. Key conclusion: CONCLUSIONS: In middle-aged and older adults with chronic constipation, a 28-day multi-strain probiotic significantly increases bowel movement frequency, improves symptoms-especially bloating-and favorably remodels gut microbi
View Original PubMed Abstract ↓

BACKGROUND & AIMS: Chronic constipation is prevalent among middle-aged and older adults, with current interventions often limited by modest efficacy and adverse effects. Probiotics have emerged as a safe, promising modality; we aimed to evaluate a 28-day multi-strain probiotic in this population using clinical and mechanistic endpoints. METHODS: We conducted a randomized, double-blind, placebo-controlled trial in adults with chronic constipation: 132 were randomized (probiotics n = 66; placebo n = 66), and 100 completed per protocol (50/50).The primary endpoint was weekly complete spontaneous bowel movements (CSBMs) at day 28; secondary endpoints included Bristol Stool Form Scale (BSFS), Patient Assessment of Constipation Symptoms (PAC-SYM), bloating scores, and multi-omics profiling (gut microbiota and fecal metabolites at days 0/14/28), with targeted fecal short-chain fatty acids (SCFAs). A pre-specified responder was defined as week-4 CSBMs ≥3 and increases ≥1 from baseline. RESULTS: At day 28, probiotics yielded higher CSBMs than placebo (4.53 ± 1.17 vs 2.40 ± 1.01, P < 0.0001), improved stool form (higher BSFS), reduced PAC-SYM, and markedly alleviated bloating (0.70 ± 0.46 vs 2.60 ± 0.93, P < 0.0001). Microbiologically, α-diversity increased and β-diversity separated between groups at days 14 and 28 (PERMANOVA P = 0.003 and 0.001); Faecalibacterium, Lactobacillus, and Bifidobacterium increased, whereas Enterobacter, Collinsella, and Oscillibacter declined. Untargeted metabolomics indicated enrichment of SCFA biosynthetic pathways (butanoate/propanoate), and targeted assays confirmed higher fecal acetate and butyrate at day 28 (P < 0.01 and P < 0.05), with no significant change in propionate or valerate (both P > 0.05). Responder rates were 88 % (44/50) with probiotics versus 26 % (13/50) with placebo; within the probiotic arm, ΔFaecalibacterium and Δbutyrate correlated positively with ΔCSBM, while ΔEnterobacter correlated negatively. CONCLUSIONS: In middle-aged and older adults with chronic constipation, a 28-day multi-strain probiotic significantly increases bowel movement frequency, improves symptoms-especially bloating-and favorably remodels gut microbi

10
CLINICAL STUDY mSystems (2026) PMID: 41609355 ↗
Adjunctive probiotic therapy sustains symptom relief in gastroesophageal reflux disease through gut microbiome-metabolome remodeling.
Clinical Trial Synthesis 2026 Randomized Controlled Trial (RCT) published in mSystems involving n = 64 participants; statistical significance reported at p = 0.017. Key conclusion: Probiotic use enriched beneficial taxa (Bifidobacterium and Lactiplantibacillus plantarum) and increased γ-aminobutyric acid, succinate, citrulline, a
View Original PubMed Abstract ↓

Proton pump inhibitors (PPIs) are standard therapy for gastroesophageal reflux disease (GERD), but long-term use causes dysbiosis, gastrointestinal side effects, and symptom relapse after discontinuation. Probiotics may offer adjunctive benefits by modulating the gut ecosystem. The study aimed to evaluate the efficacy of a multi-strain probiotic (Lihuo) with rabeprazole in GERD and its impact on gut microbiota and metabolome. A randomized, double-blind, placebo-controlled trial was conducted in 120 GERD patients assigned to receive rabeprazole with either Lihuo (n = 64) or placebo (n = 56) for 8 weeks, followed by 4 weeks of probiotic or placebo alone. The primary outcome was change in the Reflux Disease Questionnaire (RDQ) score. Secondary outcomes included Gastrointestinal Symptom Rating Scale, endoscopic healing, and multi-omics profiling (shotgun metagenomics, phageome, and untargeted/targeted metabolomics). Compared with the placebo group, the probiotic group exhibited a pronounced 36.51% reduction in RDQ scores after 12 weeks of intervention (P = 0.017), alongside a higher numerical endoscopic healing rate (36.84% vs 12.50%; P = 0.365). Metagenomics revealed enrichment of Bifidobacterium animalis, Lactiplantibacillus plantarum, and Clostridium sp900540255, with reductions in Bacteroides uniformis and Clostridium Q fessum. Metabolomics showed increased γ-aminobutyric acid, succinate, citrulline, and short-chain fatty acids levels, with interesting microbe-metabolite correlations such as Bifidobacterium animalis-γ-aminobutyric acid and Bacteroides fragilis-succinate (r ≥ 0.30, P < 0.01). Our findings support that adjunctive probiotic therapy sustains post-PPI symptom relief, associated with targeted modulation of gut microbiota and bioactive metabolites.IMPORTANCELong-term proton pump inhibitor use in gastroesophageal reflux disease (GERD) may disrupt gut microbiota and cause symptom relapse after discontinuation. We found that adjunctive probiotic therapy sustained reflux reduction post-proton pump inhibitor. Probiotic use enriched beneficial taxa (Bifidobacterium and Lactiplantibacillus plantarum) and increased γ-aminobutyric acid, succinate, citrulline, a

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