Original Article

Subject Category: Microbe-microbe and microbe-host interactions

The ISME Journal (2010) 4, 232–241; doi:10.1038/ismej.2009.112; published online 29 October 2009

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

Chenhong Zhang1, Menghui Zhang1, Shengyue Wang2, Ruijun Han3, Youfang Cao1, Weiying Hua1, Yuejian Mao1, Xiaojun Zhang1, Xiaoyan Pang1, Chaochun Wei1, Guoping Zhao2, Yan Chen3 and Liping Zhao1,4

  1. 1Laboratory of Molecular Microbial Ecology and Ecogenomics, Department of Biological Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, PR China
  2. 2Chinese National Human Genome Sequencing Centre, Shanghai, PR China
  3. 3Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, PR China
  4. 4Shanghai Centre for Systems Biomedicine, Shanghai, PR China

Correspondence: L Zhao, Laboratory of Molecular Microbial Ecology and Ecogenomics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Room 3-517, Biology Building, Minhang Campus, Shanghai 200240, PR China. E-mail: lpzhao@sjtu.edu.cn; Y Chen, Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, PR China. E-mail: ychen3@sibs.ac.cn

Received 3 August 2009; Revised 28 September 2009; Accepted 28 September 2009; Published online 29 October 2009.

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Abstract

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.

Keywords:

gut microbiota, MS, HFD, host genotype, sulphate-reducing bacteria, obesity

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