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.

Highlights

  • Publisher’s Note: MDPI stays neutralThe gastrointestinal microbiota forms an intriguing and interconnected relationship with orally ingested matter—be it food or pharmaceutical ingredients—and human physiology

  • Based on the fact that several Bacillus species have been reported to trigger gut microbial butyrate production indirectly [15,16], we aimed to identify a robust strain with documented probiotic functionalities [17,18] that can modulate the human colonic microbiota towards a pro-butyrogenic shift in its composition and activity, and to combine it with a stable, non-fiber substrate that bacteria can selectively use for butyrate production

  • As the and branched-chain fatty fatty acids (BCFA) modulation was most favourable for Bacillus subtilis DSM 323 used for all further experiments

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Summary

Introduction

Publisher’s Note: MDPI stays neutralThe gastrointestinal microbiota forms an intriguing and interconnected relationship with orally ingested matter—be it food or pharmaceutical ingredients—and human physiology. Microbiota composition and activity are affected by diet, and on the other hand dietary molecules are converted through a plethora of (microbe-specific) metabolic pathways to a partly absorbable metabolome. Examples of gut microbiotaderived metabolites with known effects on the host include phenolic acids, indole derivatives, and short-chain fatty acids (SCFA) acetate, propionate, and butyrate. Butyrate is an important energy source and differentiation factor for colonic epithelial cells, it supports the formation of mucin as well as tight junction proteins and thereby contributes to intestinal barrier integrity [1]. Butyrate can trigger anti-inflammatory signaling via binding to arylhydrocarbon, G protein-coupled receptor (GPR) 41, GPR109, and Peroxisome proliferator-activated receptor γ (PPARγ) receptors and has been related to immune and metabolic functions in the gut and beyond, including the brain. A fraction of around two percent of luminal butyrate enters the circulation [2] via with regard to jurisdictional claims in published maps and institutional affiliations

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