Abstract

Macaca fascicularis, the cynomolgus macaque, is a widely used model in biomedical research and drug development as its genetics and physiology are close to those of humans. Detailed information on the cynomolgus macaque gut microbiota, the functional interplay between the gut microbiota and host physiology, and possible similarities to humans and other mammalians is very limited. The aim of this study was to construct the first cynomolgus macaque gut microbial gene catalog and compare this catalog to the human, pig, and mouse gut microbial gene catalogs. We performed metagenomic sequencing on fecal samples from 20 cynomolgus macaques and identified 1.9 million non-redundant bacterial genes of which 39.49% and 25.45% are present in the human and pig gut bacterial gene catalogs, respectively, whereas only 0.6% of the genes are present in the mouse gut bacterial gene catalog. By contrast, at the functional levels, more than 76% Kyoto Encyclopedia of Genes and Genomes orthologies are shared between the gut microbiota of all four mammalians. Thirty-two highly abundant bacterial genera could be defined as core genera of these mammalians. We demonstrated significant differences in the composition and functional potential of the gut microbiota as well as in the distribution of predicted bacterial phage sequences in cynomolgus macaques fed either a low-fat/high-fiber diet or a high-fat/low-fiber diet. Interestingly, the gut microbiota of cynomolgus macaques fed the high-fat/low-fiber diet became more similar to the gut microbiota of humans.

Highlights

  • The intestine is home to trillions of bacteria, which in number equal or even outnumber the number of host cells [1]

  • We identified 4,202 KEGG orthology (KO) involved in membrane transport and carbohydrate metabolism that are shared among the cynomolgus macaque, human, pig, and mouse gut microbiomes

  • We constructed a gut bacterial gene catalog of M. fascicularis, the cynomolgus macaque, comprising 1,991,169 NR genes and compared it with the human, mouse, and pig gut bacterial gene catalogs. This catalog represents the first geneset generated from an nonhuman primates (NHP) and provides a comprehensive reference resource for metagenomics-based research

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Summary

Introduction

The intestine is home to trillions of bacteria, which in number equal or even outnumber the number of host cells [1]. Recent evidence links changes in the gut microbiota to certain mental disorders [13, 14]. In order to establish causality between a given alteration of the gut microbiota and disease, rodent models are most frequently used. Previous studies have clearly demonstrated that the mouse gut microbiome is very different from that of humans [15,16,17]. Detailed studies on the composition and functional capacity of the gut microbiota of the cynomolgus macaque are warranted in order to examine the potential of this model for biomedical research

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