A Synbiotic Formulation Comprising Bacillus subtilis DSM 32315 and L-Alanyl-L-Glutamine Improves Intestinal Butyrate Levels and Lipid Metabolism in Healthy Humans

Abstract

The gut microbiota is a crucial modulator of health effects elicited by food components, with SCFA (short chain fatty acids), especially butyrate, acting as important mediators thereof. We therefore developed a nutritional synbiotic composition targeted at shifting microbiome composition and activity towards butyrate production. An intestinal screening model was applied to identify probiotic Bacillus strains plus various amino acids and peptides with suitable effects on microbial butyrate producers and levels. A pilot study was performed to test if the synbiotic formulation could improve fecal butyrate levels in healthy humans. A combination of Bacillus subtilis DSM (Number of German Collection of Microorganisms and Cell Cultures) 32315 plus L-alanyl-L-glutamine resulted in distinctly increased levels of butyrate and butyrate-producing taxa (Clostridium group XIVa, e.g., Faecalibacterium prausnitzii), both in vitro and in humans. Moreover, circulating lipid parameters (LDL-, and total cholesterol and LDL/HDL cholesterol ratio) were significantly decreased and further metabolic effects such as glucose-modulation were observed. Fasting levels of PYY (Peptide YY) and GLP-1 (Glucagon-like Peptide 1) were significantly reduced. In conclusion, our study indicates that this synbiotic composition may provide an effective and safe tool for stimulation of intestinal butyrate production with effects on e.g., lipid and glucose homeostasis. Further investigations in larger cohorts are warranted to confirm and expand these findings.

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

“…As the satiety hormones glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) are implicated in nutrient sensing, it is intriguing that a multi-ingredient dietary supplement containing 2 × 10 9 CFU B. subtilis DSM 32315 reduced fasting plasma GLP-1 and PYY concentrations by 36% and 40%, respectively, after 4 weeks of daily supplementation. 57 GLP-1 is synthesized and released by enteroendocrine L cells of the intestine in response to digestion and can also be measured in the bloodstream. 58 Circulating GLP-1 concentrations were directly correlated with metabolic syndrome and obesity in a study of 140 female participants.…”

Effect of Different Functional Food Supplements on the Gut Microbiota of Prediabetic Indonesian Individuals during Weight Loss

“…Nevertheless, despite this, probiotics may affect the gut microbiota activity [51,52]. Recently, a study feeding a Bacillus probiotic with a dipeptide showed very few changes in the microbiota composition but increased the production of butyrate [53]. It would be interesting to study the latter using a metabolite analysis and meta-transcriptomics in future experiments.…”

A nutritional supplement based on a synbiotic combination of Bacillus subtilis DSM 32315 and L-alanyl-L-glutamine improves glucose metabolism in healthy prediabetic subjects – A real-life post-marketing study

“…An alternative approach is the direct application of butyrate-producing bacteria. Recently, a synbiotic-based formulation containing Bacillus subtilis DSM 32315 and L-alanyl-L-glutamine (Ala-Gln) has been developed to shift the composition and activity of the gut microbiome toward butyrate production ( 21 ). The butyrogenic activity of Ala-Gln can be attributed to glutamine which is hydrolyzed to glutamic acid and then catabolized to butyric acid.…”

“…The butyrogenic activity of Ala-Gln can be attributed to glutamine which is hydrolyzed to glutamic acid and then catabolized to butyric acid. The alanine residue increases the stability of the dipeptide, serves as a spore germination trigger, and supports Bacillus subtilis metabolism ( 21 , 22 ). Compared to known butyrate producing taxa, Bacillus is not strictly anaerobic, but aerotolerant/microaerophilic, which makes it more robust both during technological processing and gastrointestinal passage.…”

“…A pilot study showed that this synbiotic-based formulation resulted in significantly increased levels of butyrate in stool and butyrate-producing taxa. In addition, circulating lipid parameters (LDL, total cholesterol, LDL/HDL ratio) were significantly reduced and further metabolic effects such as glucose modulation were observed after the application of the synbiotic ( 21 ). Consequently, it was of major medical and scientific interest to investigate the metabolic effects of this formulation in a larger cohort.…”