The microbiome and autoimmunity: a paradigm from the gut–liver axis

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.

Saliva and Oral Diseases

“…The analysis, performed with DNA isolation and 16rRNA sequencing, revealed four genera (Bifidobacterium, Dialister, Lactobacillus, and Leptotrichia) that were different between the two groups. The results were consistent with previous studies, revealing a role of Actinobacteria and Firmicutes phila [127,128]. More interestingly, Sharma et al identified a difference in alpha diversity in patients treated with steroids, suggesting the potential role of microbiome analysis in therapeutic response.…”

Gut–Liver Axis and Inflammasome Activation in Cholangiocyte Pathophysiology

“…The Veillonella genus, which is also associated with other chronic inflammatory and fibrotic conditions, was enriched in PSC [74]. As in PSC, a microbial signature consisting of 12 genera has been identified for PBC [75]. In PBC patients, microbiota profile analysis highlighted the enrichment of the Enterobacteriaceae family, followed by Pseudomonas, Veillonella and Clostridium genera; in reverse, Oscillospira and Sutterella were less represented [76].…”

Saliva microbiome in primary Sjögren’s syndrome reveals distinct set of disease‐associated microbes

“…Autoimmunity is a consequence of complex interactions between genes and the environment (Gianchecchi & Fierabracci, ; Jörg et al, ; Miller, ) due to which etiopathogenesis of many autoimmune diseases remains an enigma. Microbes have been postulated as an aetiological factor though conclusive evidence suggesting their direct role remains elusive (Li, Selmi, Tang, Gershwin, & Ma, ; Vogelzang, Guerrini, Minato, & Fagarasan, ). Sjögren's syndrome is the second most common autoimmune disease after rheumatoid arthritis (RA) with prevalence estimated at 0.1%–4.8% targeting mainly exocrine glands as well as extraglandular epithelial tissues.…”