Abstract

Human flora-associated (HFA) mouse models allow us to design interventions for human disease research to test specific hypotheses and explore the complex commensal microbiome while avoiding the ethical limitations of using humans as models to directly study intestinal flora diseases. However, few studies have investigated the effect of a humanized diet profile (coarse-feed diet; CFD) on colonization efficiency and gut microbial diversity in HFA mice. We tested the colonization efficiency and gut microbial diversity in germ-free Kunming (KM) mice fed a CFD or a purified feed diet (PFD) at 1, 2, and 4 weeks. Although the colonization efficiencies differed significantly (67.50–70.00% vs. 72.69–85.96%) in the HFA mice, the colonization efficiency of the PFD-fed HFA mice (85.96%) was significantly higher than that of the CFD-fed mice (69.61%) at 2 weeks. At 4 weeks, the colonization efficiency of the PFD-fed mice (72.69%) was comparable to that of the CFD-fed mice (70.00%). Additionally, the gut microbial diversity of the CFD-fed HFA mice was similar to that of a human fecal donor. Regarding the Kyoto Encyclopedia of Genes and Genomes colonic microbiota metabolic pathways, the CFD-fed HFA mice showed more similarities to the human donor than to the PFD-fed mice in amino sugar and nucleotide sugar metabolism, biosynthesis of amino acids, carbon metabolism, purine metabolism, and phosphotransferase systems. In conclusion, the humanized diet profiles of the CFD and PFD could help establish human microbiotas in mice. Constructing HFA mouse models fed a CFD for 4 weeks may be useful in researching human-derived intestinal diseases.

Highlights

  • Owing to the development of high-throughput sequencing techniques and applications in mapping the human gut microbiome, using gnotobiotic animals to explore the complex commensal microbiome seems promising [1, 2]

  • The results revealed that the metabolic pathways of the colonic microbiota, including amino sugar and nucleotide sugar metabolism, biosynthesis of amino acids, carbon metabolism, purine metabolism, and phosphotransferase systems (PTS) in the coarse-feed diet (CFD)-fed mice were more similar to those of the human donor than to those of the purified feed diet (PFD)-fed mice

  • Several studies on the gut microbiota have shown that dietary factors can modulate the gut microbiota composition and functions, especially in obese patients [29]

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Summary

Introduction

Owing to the development of high-throughput sequencing techniques and applications in mapping the human gut microbiome, using gnotobiotic animals to explore the complex commensal microbiome seems promising [1, 2]. Animal models enable design interventions to test hypotheses regarding human diseases. Colonization Efficiency and Gut-Microbial Diversity [3]. Humanized animals are necessary for understanding the complex commensal microbiome and its roles in health and disease [4]. The composition of the intestinal microbiota is driven by factors such as diet [5], antibiotic therapy [6], genotype, mode of giving birth [7, 8], age [9, 10], and antibiotics [11,12,13]. Mainly controlled by diet, is a powerful environmental factor in shaping the microbial community composition [15]. Gut microbiota alterations due to dietary changes have been extensively studied [16], and gut microbiotas change rapidly when diets are diversified

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