Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN, USA; Department of Ecology, Evolution and Behavior, University of Minnesota, Minneapolis, MN, USA.
Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA.
Cell Rep. 2021 Nov 23;37(8):110057. doi: 10.1016/j.celrep.2021.110057.
The gut microbiome exhibits extreme compositional variation between hominid hosts. However, it is unclear how this variation impacts host physiology across species and whether this effect can be mediated through microbial regulation of host gene expression in interacting epithelial cells. Here, we characterize the transcriptional response of human colonic epithelial cells in vitro to live microbial communities extracted from humans, chimpanzees, gorillas, and orangutans. We find that most host genes exhibit a conserved response, whereby they respond similarly to the four hominid microbiomes. However, hundreds of host genes exhibit a divergent response, whereby they respond only to microbiomes from specific host species. Such genes are associated with intestinal diseases in humans, including inflammatory bowel disease and Crohn's disease. Last, we find that inflammation-associated microbial species regulate the expression of host genes previously associated with inflammatory bowel disease, suggesting health-related consequences for species-specific host-microbiome interactions across hominids.
肠道微生物组在人类宿主之间表现出极大的组成变化。然而,目前尚不清楚这种变化如何影响跨物种的宿主生理学,以及这种影响是否可以通过微生物对相互作用的上皮细胞中宿主基因表达的调节来介导。在这里,我们描述了人类结肠上皮细胞在体外对来自人类、黑猩猩、大猩猩和猩猩的活体微生物群落的转录反应。我们发现,大多数宿主基因表现出保守的反应,即它们对四种人类微生物组的反应相似。然而,数百个宿主基因表现出不同的反应,即它们仅对来自特定宿主物种的微生物组有反应。这些基因与人类的肠道疾病有关,包括炎症性肠病和克罗恩病。最后,我们发现与炎症相关的微生物物种调节了先前与炎症性肠病相关的宿主基因的表达,这表明在人类宿主之间,特定于物种的宿主-微生物组相互作用可能会产生与健康相关的后果。