Khachatryan Zaruhi A, Ktsoyan Zhanna A, Manukyan Gayane P, Kelly Denise, Ghazaryan Karine A, Aminov Rustam I
Laboratory of Molecular Genetics, Institute of Molecular Biology of Armenian National Academy of Sciences, Yerevan, Armenia.
PLoS One. 2008 Aug 26;3(8):e3064. doi: 10.1371/journal.pone.0003064.
The human gastrointestinal tract is inhabited by a very diverse symbiotic microbiota, the composition of which depends on host genetics and the environment. Several studies suggested that the host genetics may influence the composition of gut microbiota but no genes involved in host control were proposed. We investigated the effects of the wild type and mutated alleles of the gene, which encodes the protein called pyrin, one of the regulators of innate immunity, on the composition of gut commensal bacteria. Mutations in MEFV lead to the autoinflammatory disorder, familial Mediterranean fever (FMF, MIM249100), which is characterized by recurrent self-resolving attacks of fever and polyserositis, with no clinical signs of disease in remission.
METHODOLOGY/PRINCIPAL FINDINGS: A total of 19 FMF patients and eight healthy individuals were genotyped for mutations in the MEFV gene and gut bacterial diversity was assessed by sequencing 16S rRNA gene libraries and FISH analysis. These analyses demonstrated significant changes in bacterial community structure in FMF characterized by depletion of total numbers of bacteria, loss of diversity, and major shifts in bacterial populations within the Bacteroidetes, Firmicutes and Proteobacteria phyla in attack. In remission with no clinical signs of disease, bacterial diversity values were comparable with control but still, the bacterial composition was substantially deviant from the norm. Discriminant function analyses of gut bacterial diversity revealed highly specific, well-separated and distinct grouping, which depended on the allele carrier status of the host.
CONCLUSIONS/SIGNIFICANCE: This is the first report that clearly establishes the link between the host genotype and the corresponding shifts in the gut microbiota (the latter confirmed by two independent techniques). It suggests that the host genetics is a key factor in host-microbe interaction determining a specific profile of commensal microbiota in the human gut.
人类胃肠道中栖息着种类繁多的共生微生物群，其组成取决于宿主基因和环境。多项研究表明宿主基因可能影响肠道微生物群的组成，但尚未提出参与宿主控制的基因。我们研究了编码名为pyrin（一种先天免疫调节因子）的蛋白质的基因的野生型和突变等位基因对肠道共生细菌组成的影响。MEFV基因突变会导致自身炎症性疾病——家族性地中海热（FMF，MIM249100），其特征为反复出现可自行缓解的发热和多浆膜炎发作，缓解期无疾病临床症状。
方法/主要发现：对19名FMF患者和8名健康个体进行MEFV基因突变基因分型，并通过对16S rRNA基因文库进行测序和荧光原位杂交（FISH）分析评估肠道细菌多样性。这些分析表明，FMF患者的细菌群落结构发生了显著变化，其特征为细菌总数减少、多样性丧失以及发作期拟杆菌门、厚壁菌门和变形菌门内细菌种群的重大变化。在无疾病临床症状的缓解期，细菌多样性值与对照组相当，但细菌组成仍与正常情况有很大差异。肠道细菌多样性的判别函数分析显示，根据宿主的等位基因携带状态，存在高度特异性、明显分开且独特的分组。
结论/意义：这是第一份明确建立宿主基因型与肠道微生物群相应变化之间联系的报告（后者通过两种独立技术得到证实）。这表明宿主基因是宿主 - 微生物相互作用中的关键因素，决定了人类肠道中共生微生物群的特定特征。
