Microbiota-related Changes in Bile Acid & Tryptophan Metabolism are Associated with Gastrointestinal Dysfunction in a Mouse Model of Autism

EBioMedicine. 2017 Oct;24:166-178. doi: 10.1016/j.ebiom.2017.09.020. Epub 2017 Sep 21.

Abstract

Autism spectrum disorder (ASD) is one of the most prevalent neurodevelopmental conditions worldwide. There is growing awareness that ASD is highly comorbid with gastrointestinal distress and altered intestinal microbiome, and that host-microbiome interactions may contribute to the disease symptoms. However, the paucity of knowledge on gut-brain axis signaling in autism constitutes an obstacle to the development of precision microbiota-based therapeutics in ASD. To this end, we explored the interactions between intestinal microbiota, gut physiology and social behavior in a BTBR T+Itpr3tf/J mouse model of ASD. Here we show that a reduction in the relative abundance of very particular bacterial taxa in the BTBR gut - namely, bile-metabolizing Bifidobacterium and Blautia species, - is associated with deficient bile acid and tryptophan metabolism in the intestine, marked gastrointestinal dysfunction, as well as impaired social interactions in BTBR mice. Together these data support the concept of targeted manipulation of the gut microbiota for reversing gastrointestinal and behavioral symptomatology in ASD, and offer specific plausible targets in this endeavor.

Keywords: Autism; BTBR mouse; Bile acids; Gut microbiota; Intestinal permeability; Intestinal transit; Serotonin; Tryptophan.

MeSH terms

  • Animals
  • Autism Spectrum Disorder / complications*
  • Autism Spectrum Disorder / genetics
  • Autism Spectrum Disorder / metabolism
  • Bacteria / classification*
  • Bacteria / isolation & purification
  • Bifidobacterium / classification
  • Bifidobacterium / isolation & purification
  • Bile Acids and Salts / metabolism*
  • Disease Models, Animal
  • Gastrointestinal Diseases / genetics
  • Gastrointestinal Diseases / metabolism
  • Gastrointestinal Diseases / microbiology*
  • Gastrointestinal Tract / metabolism
  • Gastrointestinal Tract / microbiology
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • Male
  • Mice
  • Microbiota
  • Tryptophan / metabolism*

Substances

  • Bile Acids and Salts
  • Tryptophan