1.
The microbiome and autoimmunity: a paradigm from the gut-liver axis.
Li, B, Selmi, C, Tang, R, Gershwin, ME, Ma, X
Cellular & molecular immunology. 2018;15(6):595-609
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Plain language summary
The incidence of autoimmune and inflammatory diseases has been increasing worldwide. Changes in environmental factors, such as modern lifestyle, diet, antibiotics and hygiene are thought to play a critical role in the development of various autoimmune diseases. It is the mucosal microbial flora that is shaped by our environment and communicates with the innate and adaptive immune systems, and when disrupted, can lead to the loss of immune tolerance and dysregulated immune cells. This review paper provides an overview of the interactions between the intestinal microbiome and the immune system. It explains how these interactions affect host autoimmunity locally and systemically and sheds light on the molecular mechanisms, utilised by microbes that may contribute to systemic autoimmunity in genetically susceptible individuals. The links between the gut microbiome and various autoimmune diseases, such as rheumatoid arthritis, type 1 diabetes and multiple sclerosis, as well as the gut-liver axis, involving intestinal microbiome and autoimmune liver diseases, are discussed in more detail.
Abstract
Microbial cells significantly outnumber human cells in the body, and the microbial flora at mucosal sites are shaped by environmental factors and, less intuitively, act on host immune responses, as demonstrated by experimental data in germ-free and gnotobiotic studies. Our understanding of this link stems from the established connection between infectious bacteria and immune tolerance breakdown, as observed in rheumatic fever triggered by Streptococci via molecular mimicry, epitope spread and bystander effects. The availability of high-throughput techniques has significantly advanced our capacity to sequence the microbiome and demonstrated variable degrees of dysbiosis in numerous autoimmune diseases, including rheumatoid arthritis, type 1 diabetes, multiple sclerosis and autoimmune liver disease. It remains unknown whether the observed differences are related to the disease pathogenesis or follow the therapeutic and inflammatory changes and are thus mere epiphenomena. In fact, there are only limited data on the molecular mechanisms linking the microbiota to autoimmunity, and microbial therapeutics is being investigated to prevent or halt autoimmune diseases. As a putative mechanism, it is of particular interest that the apoptosis of intestinal epithelial cells in response to microbial stimuli enables the presentation of self-antigens, giving rise to the differentiation of autoreactive Th17 cells and other T helper cells. This comprehensive review will illustrate the data demonstrating the crosstalk between intestinal microbiome and host innate and adaptive immunity, with an emphasis on how dysbiosis may influence systemic autoimmunity. In particular, a gut-liver axis involving the intestinal microbiome and hepatic autoimmunity is elucidated as a paradigm, considering its anatomic and physiological connections.
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Functional interactions between the gut microbiota and host metabolism.
Tremaroli, V, Bäckhed, F
Nature. 2012;489(7415):242-9
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Plain language summary
This literature review aims to discuss evidence for the role of the gut microbiota in metabolism and possible links to obesity. Obesity and caloric intake can influence the microbiota, but whether the reverse is true in humans remains unclear. Much of the mechanisms have been determined in rodents, determining similar pathways in humans is difficult. The interplay of diet, host and gut microbiota may cause increased gut permeability (leaky gut) that could lead to an increase in inflammation that may cause obesity, fatty liver disease and insulin resistance. It is increasingly accepted that gut microbiota can contribute to diseases such as obesity, diabetes and cardiovascular disease, but exactly how and by how much remains unclear. Evidence for treating the microbiota to help with these metabolic diseases, either by pre- or probiotic supplementation, is building. However, double-blind, placebo-controlled studies are required to determine effects. The influence of the gut microbiota is a promising area, but one that needs further research.
Abstract
The link between the microbes in the human gut and the development of obesity, cardiovascular disease and metabolic syndromes, such as type 2 diabetes, is becoming clearer. However, because of the complexity of the microbial community, the functional connections are less well understood. Studies in both mice and humans are helping to show what effect the gut microbiota has on host metabolism by improving energy yield from food and modulating dietary or the host-derived compounds that alter host metabolic pathways. Through increased knowledge of the mechanisms involved in the interactions between the microbiota and its host, we will be in a better position to develop treatments for metabolic disease.