Changes in Intestinal Microbiota Are Associated with Islet Function in a Mouse Model of Dietary Vitamin A Deficiency.

Yunting Zhou,Xiaohang Wang,Wei Xu,Junming Zhou,Yumin Zhang,Yang Chen,Zilin Sun,Bo Sun,Jun Tang

doi:10.1155/2020/2354108

Abstract

Aims The underlying mechanisms involved in Vitamin A- (VA-) related changes in glucose metabolic disorders remain unclear. Recent evidence suggests that intestinal microbiota is closely linked to the metabolic syndrome. Here, we explored whether and how intestinal microbiota affects glucose homeostasis in VA-deficient diet-fed mice. Methods Six-week-old male C57BL/6 mice were randomly placed on either a VA-sufficient (VAS) or VA-deficient (VAD) diet for 10 weeks. Subsequently, a subclass of the VAD diet-fed mice was switched to a VA-deficient rescued (VADR) diet for an additional 8 weeks. The glucose metabolic phenotypes of the mice were assessed using glucose tolerance tests and immunohistochemistry staining. Changes in intestinal microbiota were assessed using 16S gene sequencing. The intestinal morphology, intestinal permeability, and inflammatory response activation signaling pathway were assessed using histological staining, western blots, quantitative-PCR, and enzyme-linked immunosorbent assays. Results VAD diet-fed mice displayed reduction of tissue VA levels, increased area under the curve (AUC) of glucose challenge, reduced glucose-stimulated insulin secretion, and loss of β cell mass. Redundancy analysis showed intestinal microbiota diversity was significantly associated with AUC of glucose challenge and β cell mass. Redundancy analysis showed intestinal microbiota diversity was significantly associated with AUC of glucose challenge and κB signaling pathway activation. Reintroduction of dietary VA to VAD diet-fed mice restored tissue VA levels, endocrine hormone profiles, and inflammatory response, which are similar to those observed following VAS-controlled changes in intestinal microbiota. Conclusions We found intestinal microbiota effect islet function via controlling intestinal inflammatory phenotype in VAD diet-fed mice. Intestinal microbiota influences could be considered as an additional mechanism for the effect of endocrine function in a VAD diet-driven mouse model.

Highlights

Vitamin A deficiency (VAD) poses a serious threat to public health in developing countries [1]
Quantitative PCR analysis of tissues from mice of VAD and VA-deficient rescued (VADR) groups showed that the mRNA levels of retinoic acid receptor α (RARα) remained unaffected in the pancreas and intestine
The AUCIPGTT-glucose, AUCIPGTT-insulin, and β cell mass appeared to be the more important parameters, whereas we found no significant correlation between the other parameters

Summary

Introduction

Vitamin A deficiency (VAD) poses a serious threat to public health in developing countries [1]. VA and its retinoid metabolism pathway play a central role in maintaining the functions of pancreatic endocrine β cells and peripheral insulin sensitivity in the adult pancreas [2, 3]. Several mechanistic studies show that VAD induces endoplasmic reticulum stress [4], causes apoptosis in pancreatic islet cells [5], inhibits activation of the insulin signaling cascade in insulin-sensitive tissues [6], and limits hepatic glucokinase activity of hepatic glucose metabolism [7]. Many studies have investigated the molecular basis of VAD-associated glucose disorders, the exact pathogenic mechanisms involved remain unknown. Intestinal microbiota and perturbations in the composition of the microbiota support numerous nutritional, metabolic, immunological, and physiological processes [8,9,10,11].

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Conclusion