The gut microbiota has been linked with chronic diseases such as obesity in humans. However, the demonstration of causality between constituents of the microbiota and specific diseases remains an important challenge in the field. In this Opinion article, using Koch's postulates as a conceptual framework, I explore the chain of causation from alterations in the gut microbiota, particularly of the endotoxin-producing members, to the development of obesity in both rodents and humans. I then propose a strategy for identifying the causative agents of obesity in the human microbiota through a combination of microbiome-wide association studies, mechanistic analysis of host responses and the reproduction of diseases in gnotobiotic animals.
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The author is grateful to J. Shen, X. Zhang, C. Zhang, Y. Zhang, N. Zhao and J. Nicholson for inspirational discussion and kind assistance during the preparation of this manuscript. The author is also grateful to the following funding bodies for supporting his study: National Nature Science Foundation of China (NSFC; grant 30730005), the Chinese 863 Program (grants 2008AA02Z315 and 2009AA02Z310), the Chinese International Cooperation Program (grants 2007DFC30450 and 075407001) and the Chinese National Science and Technology Pillar Program (grant 2006BAI11B08).
The author declares no competing financial interests.
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