The probiotic Bacillus subtilis BS50 decreases gastrointestinal symptoms in healthy adults: a randomized, double-blind, placebo-controlled trial

Abstract

Durable spore-forming probiotics are increasingly formulated into foods, beverages, and dietary supplements. To help meet this demand, the safety and efficacy of daily supplementation of Bacillus subtilis BS50 for 6 weeks was investigated in a randomized, double-blind, placebo-controlled, parallel clinical trial of 76 healthy adults. Before and during supplementation, gastrointestinal symptoms were recorded daily using a multi-symptom questionnaire. Clinical chemistry, hematology, plasma lipids, and intestinal permeability and inflammation markers were measured at baseline and end of study. Compared to placebo, 2 × 10 9 colony-forming units (CFU) BS50 per day increased the proportion of participants showing improvement from baseline to week 6 in the composite score for bloating, burping, and flatulence (47.4% vs. 22.2%), whereby the odds of detecting an improvement were higher with BS50 (OR [95% CI]: 3.2 [1.1, 8.7], p = .024). Analyses of individual gastrointestinal symptoms indicate that BS50 increased the proportion of participants showing an improvement at week 6 compared to placebo for burping (44.7% vs. 22.2%, p = .041) and bloating (31.6% vs. 13.9%, p = .071), without affecting other symptoms. There were no clinically meaningful changes in clinical chemistry, hematology, plasma lipids and intestinal permeability and other inflammation markers. In conclusion, the results suggest that dietary supplementation of 2 × 10 9 CFU Bacillus subtilis BS50 per day is a well-tolerated and safe strategy to alleviate gas-related gastrointestinal symptoms in healthy adults. Abbreviations AE adverse event; BHD bowel habits diary; BMI body mass index; BSS Bristol Stool Scale; CFU colony-forming unit; CRP C-reactive protein; FGID functional gastrointestinal disorder; GI gastrointestinal; GITQ Gastrointestinal Tolerance Questionnaire; GLP-1 glucagon-like peptide 1; GSRS Gastrointestinal Symptom Rating Scale; HDL-C high-density lipoprotein-cholesterol; IBS irritable bowel syndrome; IL-10 interleukin-10; ITT intent-to-treat; LBP lipopolysaccharide binding protein; LDL-C low-density lipoprotein-cholesterol; PP per protocol; PYY peptide YY; TG triglyceride; total-C total cholesterol

Genetic and Phenotypic Characterization of Bacillus velezensis Strain BV379 for Human Probiotic Applications

“…One potential concern, however, was the presence of a hemolysin-encoding gene in the BV379 genome. Hemolysin genes are common to Bacillaceae probiotic strains [ 118 ], including Bacillus subtilis BS50, which was shown to be safe in healthy adults following six weeks of daily oral supplementation [ 21 , 77 ]. To address the concern of potential hemolytic activity, BV379 was plated and incubated on a blood agar medium, and it was determined that BV379 does not exhibit discernable hemolytic activity.…”

“…To determine the relative amounts of enzymes produced and secreted by BV379, a series of agar-based screens for protease, amylase, cellulase, and lipase activity was performed as previously described [ 21 ]. Briefly, BV379 cultures were diluted to a 0.5 McFarland standard and plated on skim milk (SM), starch, carboxymethylcellulose (CMC), or 1% tributyrin phenol red (TPR) agar plates and incubated at 35 °C for 18–24 h.…”

“…While established probiotic strains from the bacterial Lactobacillaceae family and Bifidobacterium genus and fungal strains from the Saccharomyces genus may require protective microencapsulation to survive transit through the GI tract [ 16 , 17 , 18 ], spore-forming Bacillaceae species are generally more resistant to the harsh microenvironments of the GI tract, including acidic gastric pH, intestinal hypoxia, bile salts, and dense colonization by resident microbes [ 19 ]. Commercial probiotic strains of Bacillus subtilis and Heyndrickxia coagulans (formerly Bacillus coagulans ) have been clinically shown to support overall GI tract health and nutrient absorption in healthy adults [ 20 , 21 , 22 , 23 ] and reduce GI symptoms in individuals with mild digestive discomfort [ 20 , 21 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ], dyspepsia [ 31 , 32 ], or inflammatory bowel syndrome [ 33 , 34 , 35 , 36 , 37 ]. Additionally, Alkalihalobacillus clausii (formerly Bacillus clausii ) strains have been demonstrated to modulate immunity in several clinical trials [ 38 , 39 , 40 ].…”

Probiotic properties of Bacillus subtilis DG101 isolated from the traditional Japanese fermented food nattō

“…B. subtilis DG101 would be able to collaborate in food digestion and host metabolism because of the plethora of other hydrolytic exoenzymes with activity against macromolecules (e.g., proteins, lipids, and polysaccharides) present in the regular human diet ( Table 1C ). The beneficial gut-associated attributes of B. subtilis DG101 could be the reasons for the recognized efficacy of B. subtilis in alleviating GI discomfort, gas production, and bloating, and the improvement of the production of healthy polyunsaturated fatty acids in the gut ( VidyaLaxme et al, 2014 ; Penet et al, 2021 ; Garvey et al, 2022 ).…”

The Probiotic Bacillus subtilis MB40 Improves Immunity in a Porcine Model of Listeriosis

“…Bacillaceae strains are particularly suited for animal DFM and human probiotic products because they can be manufactured as thermostable spores that tolerate gastric acidity following oral administration [ 40 , 41 , 42 , 43 , 44 ]. Certain probiotic strains of Bacillus subtilis and Weizmannia coagulans (formerly B. coagulans ) have been clinically shown to support digestion and GI health in healthy human participants [ 45 , 46 , 47 ] and participants with symptoms of inflammatory bowel syndrome or dyspepsia [ 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ].…”