Interactions between gut microbiota, host genetics and diet relevant to development of metabolic syndromes in mice

Chenhong Zhang, Menghui Zhang, Shengyue Wang, Ruijun Han, Youfang Cao, Weiying Hua, Yuejian Mao, Xiaojun Zhang, Xiaoyan Pang, Chaochun Wei, Guoping Zhao, Yan Chen, Liping Zhao

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722 Scopus citations


Both genetic variations and diet-disrupted gut microbiota can predispose animals to metabolic syndromes (MS). This study assessed the relative contributions of host genetics and diet in shaping the gut microbiota and modulating MS-relevant phenotypes in mice. Together with its wild-type (Wt) counterpart, the Apoa-I knockout mouse, which has impaired glucose tolerance (IGT) and increased body fat, was fed a high-fat diet (HFD) or normal chow (NC) diet for 25 weeks. DNA fingerprinting and bar-coded pyrosequencing of 16S rRNA genes were used to profile gut microbiota structures and to identify the key population changes relevant to MS development by Partial Least Square Discriminate Analysis. Diet changes explained 57% of the total structural variation in gut microbiota, whereas genetic mutation accounted for no more than 12%. All three groups with IGT had significantly different gut microbiota relative to healthy Wt/NC-fed animals. In all, 65 species-level phylotypes were identified as key members with differential responses to changes in diet, genotype and MS phenotype. Most notably, gut barrier-protecting Bifidobacterium spp. were nearly absent in all animals on HFD, regardless of genotype. Sulphate-reducing, endotoxin-producing bacteria of the family, Desulfovibrionaceae, were enhanced in all animals with IGT, most significantly in the Wt/HFD group, which had the highest calorie intake and the most serious MS phenotypes. Thus, diet has a dominating role in shaping gut microbiota and changes of some key populations may transform the gut microbiota of Wt animals into a pathogen-like entity relevant to development of MS, despite a complete host genome.

Original languageEnglish (US)
Pages (from-to)232-241
Number of pages10
JournalISME Journal
Issue number2
StatePublished - Feb 2010

Bibliographical note

Funding Information:
This work was supported by the National Natural Science Foundation of China Program Grants 30730005, 30821005 and 20875061, 973 Program Grants 2007CB513002 and 2004CB518600, 863 Program Grant 2008AA02Z315, the International Cooperation Program Grants 2007DFC30450 and 075407001, and the Chinese Academy of Sciences (Knowledge Innovation Program KSCX1-YW-02).


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