Deficiency of Dietary Fiber Modulates Gut Microbiota Composition, Neutrophil Recruitment and Worsens Experimental Colitis.

Sj Shen,Remy Robert,Brooke J Wanrooy,Shu Wen Wen,Raymond Shim,Robert J Moore,Thi Thu Hao Van,Connie H Y Wong,Kathryn Prame Kumar,Michael J Hickey,Dragana Stanley

doi:10.3389/fimmu.2021.619366

Abstract

Ulcerative colitis is an inflammatory disease of the colon that is associated with colonic neutrophil accumulation. Recent evidence indicates that diet alters the composition of the gut microbiota and influences host–pathogen interactions. Specifically, bacterial fermentation of dietary fiber produces metabolites called short-chain fatty acids (SCFAs), which have been shown to protect against various inflammatory diseases. However, the effect of fiber deficiency on the key initial steps of inflammation, such as leukocyte–endothelial cell interactions, is unknown. Moreover, the impact of fiber deficiency on neutrophil recruitment under basal conditions and during inflammation in vivo is unknown. Herein, we hypothesized that a fiber-deficient diet promotes an inflammatory state in the colon at baseline and predisposes the host to more severe colitis pathology. Mice fed a no-fiber diet for 14 days showed significant changes in the gut microbiota and exhibited increased neutrophil-endothelial interactions in the colonic microvasculature. Although mice fed a no-fiber diet alone did not have observable colitis-associated symptoms, these animals were highly susceptible to low dose (0.5%) dextran sodium sulphate (DSS)-induced model of colitis. Supplementation of the most abundant SCFA, acetate, prevented no-fiber diet-mediated enrichment of colonic neutrophils and colitis pathology. Therefore, dietary fiber, possibly through the actions of acetate, plays an important role in regulating neutrophil recruitment and host protection against inflammatory colonic damage in an experimental model of colitis.

Highlights

Ulcerative colitis (UC) is a chronic and relapsing inflammatory condition with an unknown cause
no-fiber diet (NF) diet had a differential effect on the abundance of bacteria when compared to CON diet, with the microbiota in NF-fed mice composed of higher abundance of Desulfovibrio, Akkermansia, and Alistipes, and a marked reduction in the abundance of Bacteroides (Figure 1A)
We show that reduced fiber intake modifies gut microbiota composition in as little as three days and that this response continues to evolve for at least 2 weeks

Summary

Introduction

Ulcerative colitis (UC) is a chronic and relapsing inflammatory condition with an unknown cause. There are emerging studies that demonstrated the mechanisms underlying how immune responses and the development of inflammatory diseases can be altered by a fiber-deficient diet. We have previously shown that a no-fiber diet exacerbated clinical and pathological signs of experimental colitis, whereas another study found no worsening of experimental asthma [7, 8]. These studies indicate that the deleterious effects of a diet lacking fiber are likely restricted to the local colonic environment as opposed to systemic effects on the immune response. The exact underlying mechanisms of how a diet lacking fiber disrupts homeostasis and promotes inflammation prior to disease onset remain largely unknown

Methods

Results

Conclusion