Department of Integrative Biology, University of California, Berkeley, CA, 94720, USA.
Graduate Group in Microbiology, University of California, Berkeley, CA, 94720, USA.
Nat Commun. 2019 Feb 5;10(1):604. doi: 10.1038/s41467-019-08379-8.
The gut microbiota contributes to host health and fitness, and imbalances in its composition are associated with pathology. However, what shapes microbiota composition is not clear, in particular the role of genetic factors. Previous work in Caenorhabditis elegans defined a characteristic worm gut microbiota significantly influenced by host genetics. The current work explores the role of central regulators of host immunity and stress resistance, employing qPCR and CFU counts to measure abundance of core microbiota taxa in mutants raised on synthetic communities of previously-isolated worm gut commensals. This revealed a bloom, specifically of Enterobacter species, in immune-compromised TGFβ/BMP mutants. Imaging of fluorescently labeled Enterobacter showed that TGFβ/BMP-exerted control operated primarily in the anterior gut and depended on multi-tissue contributions. Enterobacter commensals are common in the worm gut, contributing to infection resistance. However, disruption of TGFβ/BMP signaling turned a normally beneficial Enterobacter commensal to pathogenic. These results demonstrate specificity in gene-microbe interactions underlying gut microbial homeostasis and highlight the pathogenic potential of their disruption.
肠道微生物群有助于宿主的健康和活力，其组成的失衡与病理学有关。然而，目前尚不清楚是什么塑造了微生物群的组成，特别是遗传因素的作用。以前在秀丽隐杆线虫中的研究定义了一个特征性的蠕虫肠道微生物群，它受到宿主遗传的显著影响。目前的工作探讨了宿主免疫和应激抵抗的中枢调节剂的作用，采用 qPCR 和 CFU 计数来测量在合成的先前分离的蠕虫肠道共生菌群落上培养的突变体中的核心微生物群分类群的丰度。这揭示了免疫功能受损的 TGFβ/BMP 突变体中肠杆菌科物种的大量繁殖，特别是肠杆菌科物种的大量繁殖。用荧光标记的肠杆菌科进行成像表明，TGFβ/BMP 发挥的控制作用主要在前肠中进行，并依赖于多组织的贡献。肠杆菌科共生菌是蠕虫肠道中的常见共生菌，有助于抵抗感染。然而，TGFβ/BMP 信号的中断将一种正常有益的肠杆菌科共生菌变成了致病性的。这些结果表明，在维持肠道微生物组平衡的基因-微生物相互作用中存在特异性，并强调了它们中断的潜在致病性。
