Abstract

SummaryThe gut microbiota can modulate human metabolism through interactions with macronutrients. However, microbiota-diet-host interactions are difficult to study because bacteria interact in complex food webs in concert with the host, and many of the bacteria are not yet characterized. To reduce the complexity, we colonize mice with a simplified intestinal microbiota (SIM) composed of ten sequenced strains isolated from the human gut with complementing pathways to metabolize dietary fibers. We feed the SIM mice one of three diets (chow [fiber rich], high-fat/high-sucrose, or zero-fat/high-sucrose diets [both low in fiber]) and investigate (1) how dietary fiber, saturated fat, and sucrose affect the abundance and transcriptome of the SIM community, (2) the effect of microbe-diet interactions on circulating metabolites, and (3) how microbiota-diet interactions affect host metabolism. Our SIM model can be used in future studies to help clarify how microbiota-diet interactions contribute to metabolic diseases.

Highlights

  • The human gut is populated with a dense and complex community of microbes, collectively known as the gut microbiota (Dethlefsen et al, 2007)

  • Studies to delineate the interactions between gut bacteria, diet, and host metabolism are challenging because (1) of the complexity and high inter-individual variability of human gut microbiota, (2) bacteria interact in complex food webs in concert with the host, and (3) the microbiota consists mainly of non-sequenced members, limiting interpretation from metagenomic and metatranscriptomic analyses

  • We showed that all ten bacteria of the simplified intestinal microbiota (SIM) community colonized each region of the gut of SIM mice on a chow diet, Eubacterium hallii was present only at a low density throughout (Figure 1A)

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Summary

Introduction

The human gut is populated with a dense and complex community of microbes, collectively known as the gut microbiota (Dethlefsen et al, 2007). A key function of microbes in the gut is to process complex carbohydrates that cannot be digested by host enzymes (Sonnenburg and Backhed, 2016) into short-chain fatty acids (SCFAs), primarily acetate, propionate, and butyrate, and organic acids such as succinate and lactate (Cummings and Macfarlane, 1991; Koh et al, 2016; Macfarlane and Macfarlane, 2012). Others have used mice colonized with a defined community of human bacteria to investigate microbemicrobe interactions (McNulty et al, 2013; Rey et al, 2013) or the interactions between microbiota, dietary fiber, and the

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