Oral treatment with Eubacterium hallii improves insulin sensitivity in db/db mice.

Shanthadevi Udayappan,Willem M De Vos,Hilde Herrema,Max Nieuwdorp,Louise Manneras-Holm,Geesje M Dallinga-Thie,Fredrik Backhed,Albert K Groen,Erik S G Stroes,Harry J Flint,Silvia H Duncan,Clara Belzer,Alice Chaplin-Scott

doi:10.1038/npjbiofilms.2016.9

Abstract

An altered intestinal microbiota composition is associated with insulin resistance and type 2 diabetes mellitus. We previously identified increased intestinal levels of Eubacterium hallii, an anaerobic bacterium belonging to the butyrate-producing Lachnospiraceae family, in metabolic syndrome subjects who received a faecal transplant from a lean donor. To further assess the effects of E. hallii on insulin sensitivity, we orally treated obese and diabetic db/db mice with alive E. hallii and glycerol or heat-inactive E. hallii as control. Insulin tolerance tests and hyperinsulinemic-euglycemic clamp experiments revealed that alive E. hallii treatment improved insulin sensitivity compared control treatment. In addition, E. hallii treatment increased energy expenditure in db/db mice. Active E. hallii treatment was found to increase faecal butyrate concentrations and to modify bile acid metabolism compared with heat-inactivated controls. Our data suggest that E. hallii administration potentially alters the function of the intestinal microbiome and that microbial metabolites may contribute to the improved metabolic phenotype.

Highlights

The prevalence of obesity and type 2 diabetes mellitus is expected to rise to 1 in 3 adult subjects having type 2 diabetes mellitus in 2050.1 The pathophysiology of these metabolic disorders is complex, involving both environmental and genetic factors affecting altered intestinal microbiota composition.[2]
The current study demonstrates that daily oral administration of E. hallii improves insulin sensitivity and increases energy metabolism in severely obese and diabetic db/db mice
Our observations that administration of increasing dosages of E. hallii did not affect body weight or food intake indicate that E. hallii treatment might be a safe and effective new probiotic strain to improve insulin sensitivity

Summary

Introduction

The prevalence of obesity and type 2 diabetes mellitus is expected to rise to 1 in 3 adult subjects having type 2 diabetes mellitus in 2050.1 The pathophysiology of these metabolic disorders is complex, involving both environmental (dietary) and genetic factors affecting altered intestinal microbiota composition.[2]. E. hallii is an anaerobic, Gram-positive, catalase-negative bacterium belonging to the Lachnospiraceae family of the phylum Firmicutes that is present in both murine and human faeces.[8]

Methods

Results

Conclusion