Galactooligosaccharides and Limosilactobacillus reuteri synergistically alleviate gut inflammation and barrier dysfunction by enriching Bacteroides acidifaciens for pentadecanoic acid biosynthesis

Nat Commun. 2024 Oct 28;15(1):9291. doi: 10.1038/s41467-024-53144-1.

Abstract

Ulcerative colitis (UC) is a debilitating inflammatory bowel disease characterized by intestinal inflammation, barrier dysfunction, and dysbiosis, with limited treatment options available. This study systematically investigates the therapeutic potential of a synbiotic composed of galactooligosaccharides (GOS) and Limosilactobacillus reuteri in a murine model of colitis, revealing that GOS and L. reuteri synergistically protect against intestinal inflammation and barrier dysfunction by promoting the synthesis of pentadecanoic acid, an odd-chain fatty acid, from Bacteroides acidifaciens. Notably, the synbiotic, B. acidifaciens, and pentadecanoic acid are each capable of suppressing intestinal inflammation and enhancing tight junction by inhibiting NF-κB activation. Furthermore, similar reduction in B. acidifaciens and pentadecanoic acid levels are also observed in the feces from both human UC patients and lipopolysaccharide-induced intestinal inflammation in pigs. Our findings elucidate the protective mechanism of the synbiotic and highlight its therapeutic potential, along with B. acidifaciens and pentadecanoic acid, for UC and other intestinal inflammatory disorders.

MeSH terms

  • Animals
  • Bacteroides* / drug effects
  • Bacteroides* / metabolism
  • Colitis, Ulcerative / chemically induced
  • Colitis, Ulcerative / drug therapy
  • Colitis, Ulcerative / immunology
  • Colitis, Ulcerative / metabolism
  • Colitis, Ulcerative / microbiology
  • Colitis, Ulcerative / pathology
  • Disease Models, Animal
  • Feces / microbiology
  • Gastrointestinal Microbiome / drug effects
  • Humans
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Limosilactobacillus reuteri* / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism
  • Oligosaccharides* / administration & dosage
  • Oligosaccharides* / pharmacology
  • Swine
  • Synbiotics* / administration & dosage
  • Tight Junctions / drug effects
  • Tight Junctions / metabolism

Substances

  • Oligosaccharides
  • NF-kappa B