Presence and Germination of the Probiotic Bacillus subtilis DE111® in the Human Small Intestinal Tract: A Randomized, Crossover, Double-Blind, and Placebo-Controlled Study

Abstract

Spore-based probiotics offer important advantages over other probiotics as they can survive the harsh gastric conditions of the stomach and bile salts in the small intestine, ultimately germinating in the digestive tract. A novel clinical trial in 11 ileostomy participants was conducted to directly investigate the presence and germination of the probiotic strain Bacillus subtilis DE111® in the small intestine. Three hours following ingestion of DE111®, B. subtilis spores (6.4 × 104 ± 1.3 × 105 CFU/g effluent dry weight) and vegetative cells (4.7 × 104 ± 1.1 × 105 CFU/g effluent dry weight) began to appear in the ileum effluent. Six hours after ingestion, spore concentration increased to 9.7 × 107 ± 8.1 × 107 CFU/g and remained constant to the final time point of 8 h. Vegetative cells reached a concentration of 7.3 × 107 ± 1.4 × 108 CFU/g at 7 h following ingestion. These results reveal orally ingested B. subtilis DE111® spores are able to remain viable during transit through the stomach and germinate in the small intestine of humans within 3 h of ingestion.

Metal-phenolic networks as tuneable spore coat mimetics

“…20 Studies have shown Bacillus strains to be capable of germination in the human gut, but the sample size was small and the data is recent. 21 Thus, we sought to employ MPN coatings as ''synthetic spore coats'' on nonsporulated cells to enable their rapid recovery in the GI tract. The importance of a healthy gut microbiome and the negative health effects of an unbalanced microbiome are well known, necessitating improved probiotics for more effective gut implantation.…”

Preclinical Safety Assessment of Bacillus subtilis BS50 for Probiotic and Food Applications

“…For example, the B. subtilis strain MB40 has been shown to be safe and support GI health in a randomized, double-blind, placebo-controlled trial of 100 healthy adults [ 17 , 35 ]. Additionally, B. inaquosorum DE111 supplementation has been shown to be safe in both adult and pediatric human subjects [ 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ]. Altogether, these studies provide a large body of clinical evidence that Bacillaceae spp., including B. subtilis , are safe for human consumption.…”

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

“…At least 6 weeks of daily supplementation with a meal is recommended for clinical trials of spore-forming strains with a primary outcome related to abdominal bloating because consumption with a meal is expected to critically promote growth of the spores and release of bioactive molecules such as antimicrobials and digestive enzymes. 16 …”

“…Spores can persist without refrigeration, survive desiccation and heat exposure, and resist the acidic and high bile salt conditions that occur throughout the mammalian GI tract. 16 , 17 Several Bacillaceae strains have been demonstrated to be safe for human consumption. For example, five Bacillus subtilis strains and six Weizmannia coagulans (formerly B. coagulans ) strains are “generally regarded as safe” (GRAS) for use in food without objection from the United States Food and Drug Administration (FDA).…”