Sex-Specific Differences in the Gut Microbiome in Response to Dietary Fiber Supplementation in IL-10-Deficient Mice.

Zhengxiao Zhang,Naomi Hotte,Aducio Thiesen,Karen L Madsen,Heekuk Park,Takanobu Higashiyama,Jae Eun Hyun,Hikaru Watanabe

doi:10.3390/nu12072088

Zhengxiao Zhang, Naomi Hotte + Show 6 more

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https://doi.org/10.3390/nu12072088

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Abstract

There is growing interest in studying dietary fiber to stimulate microbiome changes that might prevent or alleviate inflammatory bowel disease (IBD). However, dietary fiber effects have shown varying degrees of efficacy, for reasons that are unclear. This study examined whether the effects of isomaltodextrin on gut microbiota and IBD were dependent on dose or host sex, using an Interleukin (IL)-10 deficient murine colitis model. After 12 weeks, colonic IL-12p70 was depressed in male mice receiving high-dose isomaltodextrin supplementation compared to the control group (p = 0.04). Male mice receiving high-dose isomaltodextrin exhibited changes in microbial alpha-diversity, including enhanced richness and evenness (p = 0.01) and limited reduction in the relative abundance of Coprococcus (q = 0.08), compared to the control group. These microbial compositional changes were negatively associated with IL-12p70 levels in the male group (rs ≤ −0.51, q ≤ 0.08). In contrast, female mice receiving isomaltodextrin displayed a reduction in alpha-diversity and Coprococcus abundance and a high level of IL-12p70, as did the control group. Together, these results indicate that isomaltodextrin altered the gut microbial composition linking specific immune-regulatory cytokine responses, while the interactions among fiber, microbiota and immune response were dose dependent and largely sex specific. The results further indicate that interactions between environmental and host factors can affect microbiome manipulation in the host.

Highlights

Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are complex, chronic, immune-mediated inflammatory disorders of the gastrointestinal tract [1]
Our study examined the dose-dependent effects of dietary fiber on immune cytokine production, histopathology and the gut microbiota in an Interleukin 10 (IL-10) knock out (IL-10−/− ) murine colitis model
The comparison of shifts in food intake between treatment groups had no difference between groups (Figure 2C,D), the high-dose IMD group showed a significantly lower area under the curve (AUC) value for 12 weeks of food consumption than did the control group in both male and female mice (p = 0.002 and p = 0.005; Figure 2E,F) indicating a lower food consumption in mice receiving the highest dose of IMD

Summary

Introduction

Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are complex, chronic, immune-mediated inflammatory disorders of the gastrointestinal tract [1]. IBD is most prevalent in developed countries, especially in Europe and North America [2]. Increasing evidence has implicated host immune–microbial interactions and luminal microbial dysbiosis in the pathogenesis of IBD [5,6]. Several studies have reported a reduction in microbial species within the phylum Firmicutes and the genus Faecalibacterium and Roseburia, known producers of short chain fatty acids (SCFAs) [7,8,9,10]. SCFAs are a carbon energy source for intestinal epithelial cells and favor induction of regulatory

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