Of genes and microbes: solving the intricacies in host genomes

Abstract

Microbiome research is a quickly developing field in biomedical research, and we have witnessed its potential in understanding the physiology, metabolism and immunology, its critical role in understanding the health and disease of the host, and its vast capacity in disease prediction, intervention and treatment. However, many of the fundamental questions still need to be addressed, including the shaping forces of microbial diversity between individuals and across time. Microbiome research falls into the classical nature vs. nurture scenario, such that host genetics shape part of the microbiome, while environmental influences change the original course of microbiome development. In this review, we focus on the nature, i.e., the genetic part of the equation, and summarize the recent efforts in understanding which parts of the genome, especially the human and mouse genome, play important roles in determining the composition and functions of microbial communities, primarily in the gut but also on the skin. We aim to present an overview of different approaches in studying the intricate relationships between host genetic variations and microbes, its underlying philosophy and methodology, and we aim to highlight a few key discoveries along this exploration, as well as current pitfalls. More evidence and results will surely appear in upcoming studies, and the accumulating knowledge will lead to a deeper understanding of what we could finally term a “hologenome”, that is, the organized, closely interacting genome of the host and the microbiome.

Akkermansia muciniphila is a promising probiotic

“…Consequently, A. muciniphila can regulate the host's metabolism and immune function. However, the causal relationship between the microbes and host genomes is very complicated and needs to be further evaluated (Wang et al ., ,b).…”

“…Consistently, Wang et al . (,b) reported one patient with high‐grade metastatic urothelial carcinoma showed immune checkpoint inhibitors (ICI)‐associated colitis after a trial of combined CTLA‐4 and PD‐1 blockade. After ICI‐associated colitis in the patient was successfully treated with FMT, donor‐derived bacteria were observed to be effectively colonized in the patient's intestinal tract, with an obviously higher level of A. muciniphila .…”

Species identity dominates over environment in shaping the microbiota of small mammals

“…While genetic effects on the gut microbiota have been detected in laboratory and human studies (Wang et al . ), these are often rather weak, and within‐species studies typically emphasise the strong influence of environmental factors, such as diet (Carmody et al . ; Rothschild et al .…”

“…Strong environmental effects have also been reported in studies of wild animals, including seasonal and habitat differences (Maurice et al 2015;Amato et al 2016;Ren et al 2017). While genetic effects on the gut microbiota have been detected in laboratory and human studies (Wang et al 2018), these are often rather weak, and within-species studies typically emphasise the strong influence of environmental factors, such as diet (Carmody et al 2015;Rothschild et al 2018;Weissbrod et al 2018).…”

Profiling of Human Gut Virome with Oxford Nanopore Technology

“…The human gut is home to tremendous amount of microbes[1]. They inhabit different ecological niches in the gut, forming complex interaction networks between themselves and with the human cells, and the dynamic balance between gut microbiome and host is required for human health[2–6]. Studies in human cohort and mouse models, among others, have confirmed that gut microbial communities are associated with increasing number of some of metabolism diseases and infectious diseases, providing insights as well as potential targets for future monitoring and therapies[3, 7–14].…”