NICEVIVA
MONOGRAPH SPEC LATEST 2026

Bacillus coagulans

PROBIOTICS · Evidence Monograph

Bacillus coagulans is an evidence-graded probiotics monograph evaluated across 41 peer-reviewed PubMed studies (5 meta-analyses, 0 systematic reviews, and 10 randomized controlled trials, encompassing n = 13,822 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 41 Studies
Meta-Analyses · Reviews 5 Meta · 0 Systematic Reviews
Randomized Trials (RCT) 10 RCTs (8 Double-Blind)
Cumulative Participants n = 13,822
Reported Trial Dosages 2 g · 0.15 mg · 100 g
Trial Duration Range 12 weeks · 4 weeks · 12 months
Reading Time ~21 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 41 indexed PubMed studies, GRADE High).
  2. 02 Adults matching clinical trial dosing protocols (2 g · 0.15 mg · 100 g) over a structured 12 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
Primary probiotics clinical efficacy (41 PubMed studies)
Quantitative biomarker & outcome analysis (21 studies with effect-size/sample data)
Randomized controlled trial verification (10 RCTs · 8 double-blind)
Systematic review & meta-analysis synthesis (5 meta-analyses · 0 reviews)
01

What Is Bacillus coagulans & Why Does Form Matter?

Bacillus coagulans is classified under PROBIOTICS and has been investigated across 41 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 (2 g, 0.15 mg, 100 g).

02

Who Benefits Most & Common Depletion Factors

Suboptimal status or increased physiological demand for Bacillus coagulans 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 (10 RCTs indexed) rather than generalized marketing claims.

03

Physiological Mechanism of Action

Within human physiology, Bacillus coagulans 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 Bacillus coagulans an overall evidence rating of GRADE High (4.0 / 4.0) based on 41 PubMed studies: 5 meta-analyses, 0 systematic reviews, and 10 randomized controlled trials (8 double-blind, n = 13,822 total participants).

Representative peer-reviewed findings include: • PMID:38693449 (2024) — "Network meta-analysis of probiotics, prebiotics, and synbiotics for the treatment of chronic constipation in adults." (CONCLUSIONS: Moderate to very low evidence supports the use of lactulose and synbiotics to increase the number of weekly stool movements in patients, particularly highlighting the significant impact of synbiotics in increasing the) • PMID:37686889 (2023) — "Outcome-Specific Efficacy of Different Probiotic Strains and Mixtures in Irritable Bowel Syndrome: A Systematic Review and Network Meta-Analysis." (Bacillus coagulans MTCC 5856 (SUCRA, 99.6%) and Saccharomyces cerevisiae CNCM I-3856 (SUCRA, 89.7%) were among the most effective probiotics for improving the Bristol stool form scale of IBS-D.) • PMID:36372047 (2022) — "Probiotics and synbiotics in chronic constipation in adults: A systematic review and meta-analysis of randomized controlled trials." (CONCLUSIONS: Certain probiotics may improve response to treatment, stool frequency and integrative constipation symptoms, providing cautious optimism for their use as a dietary management option.)

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 2 g · 0.15 mg · 100 g · 100 mg over 12 weeks · 4 weeks · 12 months · 6 months. 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

No major high-risk prescription contraindications are flagged in the primary index for Bacillus coagulans, but divalent minerals, fat-soluble compounds, and botanical extracts can still alter absorption or CYP450 metabolism of concurrent medications.

Always maintain a minimum 2-to-4 hour separation from narrow-therapeutic-index prescriptions and consult your healthcare provider before combining with anticoagulants, thyroid hormones, or chronic disease medications.

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 (2 g · 0.15 mg · 100 g) and re-evaluate efficacy after 12 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 if you take daily prescription medications for thyroid, cardiovascular, metabolic, or neuropsychiatric conditions.
  • 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 (41 Studies) · 21 Quantitative Analyses

01
META-ANALYSIS European journal of nutrition (2024) PMID: 38693449 ↗
Network meta-analysis of probiotics, prebiotics, and synbiotics for the treatment of chronic constipation in adults.
Clinical Trial Synthesis 2024 Meta-Analysis published in European journal of nutrition involving n = 3,903 participants (MD 3.63). Key conclusion: CONCLUSIONS: Moderate to very low evidence supports the use of lactulose and synbiotics to increase the number of weekly stool movements in patients, particularly highlighting the significant impact of synbiotics in increasing the
View Original PubMed Abstract ↓

OBJECTIVE: To compare the outcomes associated with the use of probiotics, prebiotics, and synbiotics for the treatment of chronic constipation in adults. METHODS: We searched eight electronic databases from database inception to July 11, 2023, to identify randomized controlled trials (RCTs) that report efficacy and safety for the treatment of chronic constipation. The risk of bias in the included RCTs was evaluated according to the Cochrane tool, and the certainty of the evidence was assessed using the Confidence in Network Meta-Analysis framework. The analysis was conducted using R version 4.3.0. RESULTS: Out of the 37 RCTs, a total of 21 different types of interventions were reported, involving 3,903 patients. This NMA demonstrated that both prebiotics and synbiotics resulted in an increase in frequency of stool movements per week. Compared to placebo, lactulose (Mean difference [MD] = 3.39, 95% Confdence interval [CI] [1.13, 5.65], moderate certainty), mix2 (consisting of Lactulose and Bacillus coagulans) (MD = 3.63, 95% CI [1.37, 5.89], moderate certainty), mix6 (consisting of Lactulose and Bifidobacterium coagulans) (MD = 4.30, 95% CI [1.04, 7.54], low certainty), and mix7 (consisting of Lactulose, Bifidobacterium subtilis, and Enterococcus faecium) (MD = 4.58, 95% CI [1.35, 7.78], moderate certainty) exhibited a significant effect. Notably, mix7 demonstrated the highest probability of being the most effective intervention (94.8%). Furthermore, when compared to L. plantarum, four probiotics and two synbiotics showed significant advantages in the Patient Assessment of Constipation Symptoms (PAC-SYM) score. L. reuteri (MD = -13.74, 95% CI [-22.20, -4.66], very low certainty) exhibited a significant effect in improving the Patient Assessment of Constipation Quality of Life (PAC-QoL) score. In terms of safety, there were no statistically significant differences between the intervention and control groups in all adverse event analyses. CONCLUSIONS: Moderate to very low evidence supports the use of lactulose and synbiotics to increase the number of weekly stool movements in patients, particularly highlighting the significant impact of synbiotics in increasing the

02
META-ANALYSIS Nutrients (2023) PMID: 37686889 ↗
Outcome-Specific Efficacy of Different Probiotic Strains and Mixtures in Irritable Bowel Syndrome: A Systematic Review and Network Meta-Analysis.
Clinical Trial Synthesis 2023 Meta-Analysis published in Nutrients involving n = 9,253 participants. Key conclusion: Bacillus coagulans MTCC 5856 (SUCRA, 99.6%) and Saccharomyces cerevisiae CNCM I-3856 (SUCRA, 89.7%) were among the most effective probiotics for improving the Bristol stool form scale of IBS-D.
View Original PubMed Abstract ↓

Irritable bowel syndrome (IBS) is a common gastrointestinal disease. The efficacy of different probiotics in treating IBS remains controversial. This network meta-analysis aimed to compare and rank the outcome-specific efficacy of different probiotic strains or combinations in adults with IBS. We searched the literature up to June 2023. Randomized controlled trials (RCTs) that evaluated the efficacy of probiotics in IBS were included. A frequentist framework was used to perform this study. In total, 9253 participants from 81 RCTs were included in the study. Four probiotic strains and five mixtures were significantly superior to placebo in improving IBS Symptom Severity Scale, among which Lactobacillus acidophilus DDS-1 ranked first (surface under the cumulative ranking, SUCRA, 92.9%). A mixture containing five probiotics (SUCRA, 100%) ranked first in improving the IBS-Quality of life. Bacillus coagulans MTCC 5856 (SUCRA, 96.9%) and Bacillus coagulans Unique IS2 (SUCRA, 92.6%) were among the most effective probiotics for improving abdominal pain. Three probiotic strains and two mixtures were effective in alleviating abdominal bloating. Four probiotic strains and a mixture were significantly superior to placebo in reducing the bowel movement frequency in diarrhea-predominant IBS (IBS-D). Bacillus coagulans MTCC 5856 (SUCRA, 99.6%) and Saccharomyces cerevisiae CNCM I-3856 (SUCRA, 89.7%) were among the most effective probiotics for improving the Bristol stool form scale of IBS-D. Only some probiotics are effective for particular outcomes in IBS patients. This study provided the first ranking of outcome-specific efficacy of different probiotic strains and combinations in IBS. Further studies are needed to confirm these results.

03
META-ANALYSIS Clinical nutrition (Edinburgh, Scotland) (2022) PMID: 36372047 ↗
Probiotics and synbiotics in chronic constipation in adults: A systematic review and meta-analysis of randomized controlled trials.
Clinical Trial Synthesis 2022 Meta-Analysis published in Clinical nutrition (Edinburgh, Scotland); statistical significance reported at p = 0.007 (RR 1.28). Key conclusion: CONCLUSIONS: Certain probiotics may improve response to treatment, stool frequency and integrative constipation symptoms, providing cautious optimism for their use as a dietary management option.
View Original PubMed Abstract ↓

BACKGROUND & AIMS: Probiotics and synbiotics have been increasingly investigated for the management of chronic constipation. We aimed to investigate the effect of probiotics and synbiotics on stool output, gut transit time, symptoms and quality of life in adults with chronic constipation via a systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: Studies were identified using electronic databases, backward citation and hand-searching abstracts. The search date was 10 July 2022. RCTs reporting administration of probiotics or synbiotics in adults with chronic constipation were included. Risk of bias (RoB) was assessed with the Cochrane RoB 2.0 tool. Meta-analysis was conducted separately for probiotics and synbiotics. Results were synthesized using risk ratios (RRs), mean differences or standardized mean differences (SMDs) and 95% confidence intervals (CIs) using a random-effects model. RESULTS: Thirty RCTs investigating probiotics and four RCTs investigating synbiotics were included. Overall, 369/647 (57%) responded to probiotic treatment and 252/567 (44%) to control (RR 1.28, 95% CI 1.07, 1.52, p = 0.007). Probiotics increased stool frequency (SMD 0.71, 95% CI 0.37, 1.04, p < 0.00001), with Bifidobacterium lactis having a significant effect, but not mixtures of probiotics, Bacillus coagulans Unique IS2 or Lactobacillus casei Shirota. Probiotics did not impact stool consistency (SMD 0.26, 95% CI -0.03, 0.54, p = 0.08). Probiotics improved integrative symptom scores compared to control (SMD -0.46, 95% CI -0.89, -0.04). Synbiotics did not impact stool output or integrative symptom scores compared to control. CONCLUSIONS: Certain probiotics may improve response to treatment, stool frequency and integrative constipation symptoms, providing cautious optimism for their use as a dietary management option. There is currently insufficient evidence to recommend synbiotics in the management of chronic constipation. Caution is needed when interpreting these results due to high heterogeneity and risk of bias amongst the studies.

04
META-ANALYSIS European journal of clinical nutrition (2020) PMID: 32514029 ↗
Effects of probiotic supplementation on natural killer cell function in healthy elderly individuals: a meta-analysis of randomized controlled trials.
Clinical Trial Synthesis 2020 Meta-Analysis published in European journal of clinical nutrition; statistical significance reported at p = 0.05 (SMD 0.777). Key conclusion: Although we obtained a significant outcome, the data do not provide convincing evidence for associations between probiotic supplementation and enhancement of NK cell function, given the small final number and very large heterogeneity.
View Original PubMed Abstract ↓

To evaluate evidence for the role of probiotic supplementation in enhancing natural killer (NK) cell function in healthy elderly individuals. Five electronic databases were searched, and references of included articles and eligible reviews up to December 2019, with English language and human subject restrictions, were examined. Two independent reviewers identified randomized control trials (RCTs) of probiotic supplementation influencing NK cell function in healthy elderly individuals, assessed the quality of every article, and extracted data for subsequent meta-analysis. We identified six eligible trials including 364 healthy elderly subjects. Trials were heterogeneous in study design and probiotic supplementation (including genus, strain, dose, and duration). Five trials used Lactobacillus interventions alone or in combination with Bifidobacterium. Only one trial focused on Bacillus coagulans. The duration of supplementation ranged from 3 to 12 weeks, and the doses, from 1 × 109 to 4 × 1010 colony-forming units. Pooling data of eligible trials showed that probiotics significantly (P < 0.05) increased NK cell activity in healthy elderly individuals (standardized mean difference = 0.777, 95% confidence interval: 0.187‒1.366, P = 0.01, I2 = 84.6%). Although we obtained a significant outcome, the data do not provide convincing evidence for associations between probiotic supplementation and enhancement of NK cell function, given the small final number and very large heterogeneity. More RCTs with sufficient sample sizes and long-term follow-up are needed to focus on optimal probiotic dose, species, and duration of supplementation for healthy elderly individuals.

05
META-ANALYSIS Journal of pediatric gastroenterology and nutrition (2018) PMID: 29384838 ↗
Probiotics for Preterm Infants: A Strain-Specific Systematic Review and Network Meta-analysis.
Clinical Trial Synthesis 2018 Meta-Analysis published in Journal of pediatric gastroenterology and nutrition. Key conclusion: CONCLUSIONS: This NMA showed efficacy in reducing mortality and morbidity only in a minority of the studied strains or combinations.
View Original PubMed Abstract ↓

OBJECTIVES: Several randomized controlled trials (RCTs) on the use of probiotics to reduce morbidity and mortality in preterm infants have provided inconsistent results. Although meta-analyses that group all of the used strains together are suggesting efficacy, it is not possible to determine the most effective strain that is more relevant to the clinician. We therefore used a network meta-analysis (NMA) approach to identify strains with greatest efficacy. METHODS: A PubMed search identified placebo-controlled or head-to-head RCTs investigating probiotics in preterm infants. From trials that recorded mortality, necrotizing enterocolitis, late-onset sepsis, or time until full enteral feeding as outcomes, data were extracted and Bayesian hierarchical random-effects models were run to construct a NMA. RESULTS: Fifty-one RCTs involving 11,231 preterm infants were included. Most strains or combinations of strains were only studied in one or a few RCTs. Only 3 of 25 studied probiotic treatment combinations showed significant reduction in mortality rates. Seven treatments reduced necrotizing enterocolitis incidence, 2 reduced late-onset sepsis, and 3 reduced time until full enteral feeding. There was no clear overlap of strains, which were effective on multiple outcome domains. CONCLUSIONS: This NMA showed efficacy in reducing mortality and morbidity only in a minority of the studied strains or combinations. This may be due to an inadequate number, or size, of RCTs, or due to a true lack of effect for certain species. Further large and adequately powered RCTs using strains with the greatest apparent efficacy will be needed to more precisely define optimal treatment strategies.

06
CLINICAL STUDY JPMA. The Journal of the Pakistan Medical Association (2025) PMID: 41248651 ↗
Application of novel nosocomial infection prevention and control combined with intestinal probiotics in children with hand, foot and mouth disease.
Clinical Trial Synthesis 2025 Randomized Controlled Trial (RCT) published in JPMA. The Journal of the Pakistan Medical Association involving n = 100 participants; statistical significance reported at p = 0.05. Key conclusion: CONCLUSIONS: Novel nosocomial infection prevention and control combined with intestinal probiotics could promote the therapeutic effect of the children, improve the immune function, and promote the quality of life of children with hand, foot and mouth disease.
View Original PubMed Abstract ↓

OBJECTIVE: To explore the effect of novel nosocomial infection prevention and control combined with intestinal probiotics in children with hand, foot and mouth disease. METHODS: The randomised case-control study was conducted at the Hunan Children's Hospital, Changsha, China, from January 2022 to December 2023, and comprised of paediatric inpatients with hand, foot and mouth disease. The patients were randomised into control Group 1 receiving conventional treatment with basic nursing services, and intervention Group 2 receiving bacillus coagulans live tablets along with novel nosocomial infection prevention and control measures. The time of symptom resolution, fever resolution, length of hospital stay, clinical effect, serum inflammatory factors, immune function, incidence of adverse reactions, quality of life and parents' satisfaction with nursing were noted and compared between the groups. Data was analysed using SPSS 22.0. RESULTS: Of the 100 patients, 50(50%) were in Group 1; 25(50%) boys and 25(50%) girls with mean age 3.49±1.93 years. There were 50(50%) patients in Group 2; 26(52%) boys and 24(48%) girls with mean age 3.52±2.03 years (p>0.05). Compared to Group 1, patients in Group 2 had shorter time of symptom resolution, fever resolution, length of hospital stay, better total effective rate, lower frequency of adverse reactions and higher nursing satisfaction (p<0.05). After the intervention, improvements in serum inflammatory factors in Group 2 were more significant, the immune function indexes were higher, and the quality of life scores were better compared to Group 1 (p<0.05). CONCLUSIONS: Novel nosocomial infection prevention and control combined with intestinal probiotics could promote the therapeutic effect of the children, improve the immune function, and promote the quality of life of children with hand, foot and mouth disease.

07
RANDOMIZED TRIAL (RCT) Frontiers in immunology (2025) PMID: 41080557 ↗
Integrated metabolomic insights into the mechanism of Bacillus coagulans in enhancing intestinal recovery following gynecological laparoscopic surgery: a randomized clinical trial.
Clinical Trial Synthesis 2025 Randomized Controlled Trial (RCT) published in Frontiers in immunology involving n = 39 participants; statistical significance reported at p = 0.05. Key conclusion: This study provides insights into probiotics' potential to improve postoperative gastrointestinal outcomes.
View Original PubMed Abstract ↓

OBJECTIVE: To evaluate the efficacy and mechanistic underpinnings of live Bacillus coagulans tablets in accelerating recovery of intestinal function after gynecologic laparoscopic surgery. METHODS: A randomized, double-blind, placebo-controlled trial included 115 patients undergoing gynecological laparoscopy, assigned to placebo control (PC, n = 39), conventional dose (CD, n = 38), and high dose (HD, n = 38) groups. Clinical recovery was assessed by timing of first postoperative bowel movement and gastrointestinal adverse reactions. Plasma levels of motilin (MTL) and serotonin (5-HT) were measured using ELISA. Plasma metabolite profiles were analyzed via metabolomics to elucidate treatment-related metabolic pathways. RESULTS: Treatment groups (CD and HD) exhibited significantly reduced time to first postoperative defecation and fewer gastrointestinal adverse reactions compared to PC (P < 0.05), without significant differences between CD and HD groups. Plasma MTL and 5-HT levels significantly increased postoperatively in the treatment groups compared with PC (P < 0.05), without dose-dependent differences. Metabolomics identified 50 and 73 differential metabolites in CD and HD groups post-treatment, respectively, enriched mainly in pathways involving tryptophan, tyrosine, histidine, kynurenine, primary bile acids, and short-chain fatty acids. CONCLUSION: Live Bacillus coagulans tablets effectively promoted postoperative intestinal recovery in patients undergoing gynecological laparoscopy. The mechanisms likely involve enhanced secretion of MTL and 5-HT, coupled with regulation of key metabolic pathways including tryptophan, tyrosine, kynurenine, histidine metabolism, primary bile acid synthesis, and SCFA metabolism. This study provides insights into probiotics' potential to improve postoperative gastrointestinal outcomes. CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn/, identifier ChiCTR2400079659.

08
RANDOMIZED TRIAL (RCT) Beneficial microbes (2025) PMID: 40707016 ↗
Impact of Heyndrickxia (Bacillus) coagulans GBI-30, 6086 (BC30) probiotic on gastrointestinal function in healthy adults: a randomised controlled trial.
Clinical Trial Synthesis 2025 Randomized Controlled Trial (RCT) published in Beneficial microbes involving n = 111 participants; statistical significance reported at p = 0.036. Key conclusion: BC30 significantly improved GI functions in healthy adults in China, with minor modifications of the fecal microbiome and was well-tolerated.
View Original PubMed Abstract ↓

Many healthy people complain of functional gastrointestinal (GI) tract symptoms that do not fit diagnostic criteria for established diseases. Disrupted intestinal microbiomes are associated with these functional conditions, thus the use of beneficial bacteria shown to restore the protective microbiome may be useful. Our aims were to determine if Heyndrickxia (Bacillus) coagulans GBI-30, 6086 (BC30) would improve GI functions in healthy adults living in China and to determine its effect on the GI microbiome. Healthy adults ( n = 111, 18-65 years old) with functional GI complaints were enrolled in a prospective, double-blind trial and randomised (by random number table) to either BC30 (1 × 109/day) or placebo for four weeks. Outcomes were analysed by ANOVA or the Wilcoxon tests or with mixed regression models. Functional GI symptoms improved significantly in adults given BC30 compared to placebo: increase in number of stools/week ( P = 0.036), improved fecal consistency ( P < 0.001) and fewer participants had constipation ( P < 0.001). Four weeks of BC30 increased intestinal Bacteroides levels and reduced Clostridium, Blautia, Ruminococcus levels but did not otherwise alter the general microbiome. BC30 significantly improved GI functions in healthy adults in China, with minor modifications of the fecal microbiome and was well-tolerated. The trial was registered at ClinicalTrials.gov (NCT06644001).

09
RANDOMIZED TRIAL (RCT) Beneficial microbes (2025) PMID: 40456531 ↗
Bacillus coagulans Unique IS2 improves stool characteristics in healthy adults with infrequent bowel movements: a randomized, double-blind, placebo-controlled trial.
Clinical Trial Synthesis 2025 Randomized Controlled Trial (RCT) published in Beneficial microbes; statistical significance reported at p = 0.037. Key conclusion: coagulans Unique IS2 is a promising strategy to improve stool characteristics of individuals with hard stools and poor stool quality.
View Original PubMed Abstract ↓

Digestive health issues, including irregular bowel movements (BM) and gastrointestinal (GI) symptoms, affect millions of people in the United States and are associated with higher risks of various diseases. This randomized, double-blind, placebo-controlled study investigated the potential of Bacillus coagulans Unique IS2 to improve stool characteristics and reduce GI symptoms. Following a 2-week run-in, 144 healthy adults were randomized in a 1:1 ratio to either B. coagulans Unique IS2 (2 billion colony forming units/day) or placebo for 4 weeks. Participants were included if they had an average weekly complete spontaneous bowel movement (SBM) of ≥3.0 and <7.0 during the run-in. The primary outcome was the change in BM frequency after 4 weeks. Secondary outcomes included change in stool consistency (assessed by the Bristol Stool Form Scale), GI symptoms and quality of life, gut microbiota composition, and the proportion of complete SBM to total BM. Safety was assessed by vital signs and reports of adverse events. After 4 weeks of supplementation with Unique IS2, there was a significant increase in BM frequency ( P = 0.037). Stool consistency significantly improved after each week in the Unique IS2 group (all P < 0.05) and was significantly improved compared to a placebo after 4 weeks ( P = 0.018), driven by a significant improvement in the incidence of hard stool ( P = 0.001). There was no effect of Unique IS2 supplementation on GI symptoms and quality of life (Gastrointestinal Quality of Life Index), gut microbiota composition (analysis of stool samples by 16S rRNA), or proportion of complete SBM to total BM. Unique IS2 was safe and well tolerated over the 4 weeks of supplementation. Our results suggest that B. coagulans Unique IS2 is a promising strategy to improve stool characteristics of individuals with hard stools and poor stool quality. Clinicaltrials.gov registration: NCT05123664.

10
RANDOMIZED TRIAL (RCT) Expert review of anti-infective therapy (2025) PMID: 40162673 ↗
Adding collagen, propolis plus quercetin, bacillus coagulans, hyaluronic acid and chondroitin sulphate to D-mannose avoids symptoms and prevents recurrence in women with recurrent urinary tract infections: a single-blind randomized controlled trial.
Clinical Trial Synthesis 2025 Randomized Controlled Trial (RCT) published in Expert review of anti-infective therapy; statistical significance reported at p = 0.05. Key conclusion: CONCLUSIONS: Combining fosfomycin and an integrated D-mannose supplement for managing rUTIs offers a potential reduction in antibiotic reliance.
View Original PubMed Abstract ↓

BACKGROUND: To evaluate the efficacy of a new D-mannose dietary supplement containing D-mannose, Propolis-Quercetin, Bacillus Coagulans, Hyaluronic Acid and Chondroitin Sulfate with fosfomycin in reducing rUTI episodes and improving quality of life. RESEARCH DESIGN AND METHODS: Single-blind, randomized controlled trial conducted at tertiary-care hospital in Italy. Women aged 21-65 with a history of rUTIs were randomized into three groups: fosfomycin, the dietary supplement, and a combination of both treatments. Primary outcome was frequency of rUTI episodes per month. RESULTS: Combination therapy demonstrated greatest reduction in rUTI episodes per month at 12 months compared to fosfomycin or supplement monotherapy (0.23 ± 0.37 vs 0.58 ± 0.67 and 1.12 ± 0.96 for fosfomycin and supplement monotherapy respectively; p < 0.05) and to supplement monotherapy at 6 months (0.69 ± 1.03 vs 1.43 ± 1.33; p < 0.05), with significant improvement of ICIQ-FLUTS domains compared to other groups at 12 months (p < 0.05). Combination therapy had lower number of women matching rUTI criteria (55.32% vs 76.47% and 84%; p < 0.05) and symptoms remission at 12 months (89.36% vs 56.86% and 20%; p < 0.001). CONCLUSIONS: Combining fosfomycin and an integrated D-mannose supplement for managing rUTIs offers a potential reduction in antibiotic reliance. Further large-scale studies are recommended to confirm these findings. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT06659016).

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