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

Overview

Journal EBioMedicine

Specialty Biomedical Engineering

Date 2017 Oct 3

PMID 28965876

Citations 151

Authors

Anna V Golubeva

Susan A Joyce

Gerard Moloney

Aurelijus Burokas

Eoin Sherwin

Silvia Arboleya

Ian Flynn

Dmitry Khochanskiy

Angela Moya-Perez

Veronica Peterson

Kieran Rea

Kiera Murphy

Olga Makarova

Sergey Buravkov

Niall P Hyland

Catherine Stanton

Gerard Clarke

Cormac G M Gahan

Timothy G Dinan

John F Cryan

Affiliations

Soon will be listed here.

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 TItpr3/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.

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