上述しましたように、ヒト腸内細菌叢の主要コンポーネントのいくつかは遺伝的に決定されているということを、大規模な数の双子ペアのセットのメタゲノム解析で明らかにしました。
The 1653rd Biological Symposium
Date: Tuesday, March 5, 2013
Time: 10:30 - 12:00
Speaker: Andrew G. Clark (Department of Molecular Biology & Genetics, Cornell University)
Title: Genome screen for human variants that influence gut microbiome composition
Abstract:
There is widespread interest in the importance of the human gut microflora in maintenance of health. The specific composition of the gut microbiota differs markedly among individuals and is increasingly viewed as a risk factor in chronic diseases such as obesity, inflammatory bowel disease, and diabetes. The development of possible therapies will require a deeper understanding of the factors that shape the microbiota, including age, diet, host physiology and health, and their interactions. Importantly, the role of the host genotype in modulating microbial community composition remains to be elucidated. In animal models, host gene deletions often result in shifts in microbiota composition, and a recent quantitative trait locus mapping study linked specific genetic loci with microbial abundances. In humans however, recent studies failed to reveal any differences in the concordance of microbial community composition between monozygotic (MZ) and dizygotic (DZ) twin pairs, suggesting a lack of evidence for host genotype on the microbiome. In an effort to improve our understanding of possible roles of human genetic variation on gut microbiota, we characterized the gut microbial communities of 165 DZ twin pairs and 118 MZ twin pairs. We show that specific components of the bacterial community are heritable, and that abundances of specific taxa are associated with specific genetic variants in the human genome, particularly near genes related to cytokine signaling in the immune system, type II interferon signaling, and T-cell receptor signaling. These findings indicate that the composition of the microbiota of an individual results from environmental influences, but that host genetics select on this bacterial assemblage in predictable ways. Confirmation was found in the data from the Human Microbiome Project after inference of host genotypes from the metagenomics sequence reads. The integration of the microbiome into models of disease risk, as an environmentally acquired factor that is influenced by host genetics, should improve understanding of many chronic inflammatory conditions.
Host: Hiroshi Akashi
