Gut Microbiota-Modulated Metabolomic Profiling Shapes the Etiology and Pathogenesis of Autoimmune Diseases

Abstract

Autoimmunity is a complex and multifaceted process that contributes to widespread functional decline that affects multiple organs and tissues. The pandemic of autoimmune diseases, which are a global health concern, augments in both the prevalence and incidence of autoimmune diseases, including type 1 diabetes, multiple sclerosis, and rheumatoid arthritis. The development of autoimmune diseases is phenotypically associated with gut microbiota-modulated features at the molecular and cellular levels. The etiology and pathogenesis of autoimmune diseases comprise the alterations of immune systems with the innate and adaptive immune cell infiltration into specific organs and the augmented production of proinflammatory cytokines stimulated by commensal microbiota. However, the relative importance and mechanistic interrelationships between the gut microbial community and the immune system during progression of autoimmune diseases are still not well understood. In this review, we describe studies on the profiling of gut microbial signatures for the modulation of immunological homeostasis in multiple inflammatory diseases, elucidate their critical roles in the etiology and pathogenesis of autoimmune diseases, and discuss the implications of these findings for these disorders. Targeting intestinal microbiome and its metabolomic associations with the phenotype of autoimmunity will enable the progress of developing new therapeutic strategies to counteract microorganism-related immune dysfunction in these autoimmune diseases.

Intestinal microbiota composition of children with infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and multisystem inflammatory syndrome (MIS-C)

“…Although zonulin levels were not included in the present study, they were found to be high in MIS-C cases in a previous study [ 52 ]. In rheumatoid arthritis patients, it was shown that Prevotella activated the TLR-2 receptor of intestinal epithelial cells, stimulated the release of proinflammatory cytokines, such as IL-1β, IL-6, and IL-23, supported the activation of Th17 cells that lead to IL-17 production, and played a role in inflammation [ 53 , 54 ]. In our study, we found that Prevotella at the genus level and Prevotella tannerae were significantly dominant in the intestine at the species level.…”

Traditional Tibetan Medicine Twenty-Five Wei’er Tea Pills Ameliorate Rheumatoid Arthritis Based on Chemical Crosstalk Between Gut Microbiota and the Host

“…An increasing number of studies have shown the effect of gut microbiota on the immune system ( de Oliveira et al, 2017 ; Castro Rocha et al, 2020 ), metabolic homeostasis ( Wu et al, 2020 ; Tsai et al, 2021 ), and gastrointestinal integrity ( Owen and Mohamadzadeh, 2013 ; Guerreiro et al, 2018 ). Studies conducted in recent years have suggested that the abnormal immune response of RA may be associated with the imbalance of gut microbiota ( Xu et al, 2020 ; Brandl et al, 2021 ; Li and Wang, 2021 ).…”

“…The imbalance of gut microbiota may lead to changes in metabolomic profiling in the human body which accounts for etiology of autoimmune diseases ( Kim et al, 2017 ; Tsai et al, 2021 ; Yang and Cong, 2021 ). Metabolomics, the systematic study of the sets of metabolites in an organism, is an excellent tool to provide further insight or scientific basis into specific pathogeneses as well as the mechanism of actions of botanical medicines ( Marchev et al, 2021 ; Oyenihi et al, 2021 ).…”

A Final Frontier in Environment-Genome Interactions? Integrated, Multi-Omic Approaches to Predictions of Non-Communicable Disease Risk

“…The microbiome, and by extension, the metagenome and metatranscriptome, is variable, depending on many environmental factors, such as anti- and probiotic use, age, diet, environment and physical activity levels. Despite few causal examples, it is widely recognized that changes in the gut microbiota are associated with the onset and progression of non-communicable diseases [reviewed in ( Noce et al, 2019 )], including autoimmune diseases such as multiple sclerosis (MS) and rheumatoid arthritis [RA, ( Tsai et al, 2021 )]. Comprehensive investigations of the microbiome are, by their nature, integrative requiring analyses of the metagenome and metatranscriptome; direct and indirect interactions between the microbiome and the host, and environment-microbe-metabolism interactions ( Kurilshikov et al, 2019 ).…”

“…This means that the metabolome may contribute to our understanding of the developmental basis of disease by refining our ability to assign functional changes to environmental exposures. Recent studies also demonstrate the value of integrating metabolome with microbiome data to profile disease pathogenesis, for example, a recent review of autoimmune disease describes how the microbiome and associated metabolic profile are altered by ‘modern’ lifestyles, which is impacting on inflammatory responses ( Tsai et al, 2021 ). Given that the metabolome itself is the end product of cellular processes, it stands to reason that, like the proteome, it can be indirectly altered by environmentally-induced genomic, epigenetic, structural and microbiotic changes.…”