Abstract

The intestinal microbiota is critical for maintaining homeostasis. Dysbiosis, an imbalance in the microbial community, contributes to the susceptibility of several diseases. Many factors are known to influence gut microbial composition, including diet. We have previously shown that fecal immunoglobulin (Ig) A levels are decreased in mice fed a diet free of aryl hydrocarbon receptor (AhR) ligands. Here, we hypothesize this IgA decrease is secondary to diet-induced dysbiosis. We assigned mice to a conventional diet, an AhR ligand-free diet, or an AhR ligand-free diet supplemented with the dietary AhR ligand indole-3-carbinol (I3C). We observed a global alteration of fecal microbiota upon dietary AhR ligand deprivation. Compared to mice on the conventional diet, family Erysipelotrichaceae was enriched in the feces of mice on the AhR ligand-free diet but returned to normal levels upon dietary supplementation with I3C. Faecalibaculum rodentium, an Erysipelotrichaceae species, depleted its growth media of AhR ligands. Cultured fecal bacteria from mice on the AhR ligand-free diet, but not the other two diets, were able to alter IgA levels in vitro, as was F. rodentium alone. Our data point to the critical role of AhR dietary ligands in shaping the composition and proper functioning of gut microbiota.

Highlights

  • The aryl hydrocarbon receptor (AhR) is a transcription factor that was originally studied for its role in mediating the metabolism of its xenobiotic ligands

  • We have shown previously that mice fed a diet deficient in AhR ligands have lower levels of fecal immunoglobulin (Ig) A compared with mice on a conventional chow diet[14]

  • Fecal microbiota composition is altered is the absence of dietary AhR ligands

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Summary

Introduction

The aryl hydrocarbon receptor (AhR) is a transcription factor that was originally studied for its role in mediating the metabolism of its xenobiotic ligands. Mice deficient in caspase recruitment domain 9 (Card9), an inflammatory bowel disease (IBD) susceptibility gene, harbor a dysbiotic gut microbiota that is unable to metabolize tryptophan into AhR ligands, leading to more severe chemically-induced colitis[8]. Dietary sources of AhR ligands that are not directly produced by the microbiota are capable of modulating the gut environment. Mice on a diet low in AhR ligands harbor a higher gut bacterial load compared with mice on a control diet, and dietary I3C is sufficient to lower the bacterial load to normal levels[13]. We hypothesized that an AhR ligand-free diet would alter the composition of the microbiota, and that this altered microbiota directly contributes to the low fecal IgA levels characteristic of mice on this diet. We sought to identify potential commensal species capable of shaping luminal IgA levels

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