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Microbe-metabolite-host axis,two-way action in the pathogenesis and treatment of human autoimmunity
Authors:Xiang Meng  Hao-Yue Zhou  Hui-Hui Shen  Eniya Lufumpa  Xiao-Mei Li  Biao Guo  Bao-Zhu Li
Affiliation:1. School of Stomatology, Anhui Medical University, Hefei, Anhui, China;2. Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China;3. Anhui Province Key Laboratory of Major Autoimmune Diseases, 81 Meishan Road, Hefei, Anhui, China;4. Department of Clinical Medicine, The second School of Clinical Medicine, Anhui Medical University, Anhui, Hefei, China;5. Institute of Applied Health Research, University of Birmingham, Birmingham, UK;6. Department of Rheumatology & Immunology, Anhui Provincial Hospital, Anhui, Hefei, China;7. The Second Affiliated Hospital of Anhui Medical University, Anhui, Hefei, China
Abstract:The role of microorganism in human diseases cannot be ignored. These microorganisms have evolved together with humans and worked together with body's mechanism to maintain immune and metabolic function. Emerging evidence shows that gut microbe and their metabolites open up new doors for the study of human response mechanism. The complexity and interdependence of these microbe-metabolite-host interactions are rapidly being elucidated. There are various changes of microbial levels in models or in patients of various autoimmune diseases (AIDs). In addition, the relevant metabolites involved in mechanism mainly include short-chain fatty acids (SCFAs), bile acids (BAs), and polysaccharide A (PSA). Meanwhile, the interaction between microbes and host genes is also a factor that must be considered. It has been demonstrated that human microbes are involved in the development of a variety of AIDs, including organ-specific AIDs and systemic AIDs. At the same time, microbes or related products can be used to remodel body's response to alleviate or cure diseases. This review summarizes the latest research of microbes and their related metabolites in AIDs. More importantly, it highlights novel and potential therapeutics, including fecal microbial transplantation, probiotics, prebiotics, and synbiotics. Nonetheless, exact mechanisms still remain elusive, and future research will focus on finding a specific strain that can act as a biomarker of an autoimmune disease.
Keywords:A-LPS  anionic lipopolysaccharide  AMP  anti-microbial peptide  AHR  aryl hydrocarbon receptor  AIDs  autoimmune diseases  BAs  bile acids  CYP7A1  cholesterol 7ɑ-hydroxylase  DCs  dendritic cells  ERK  extracellular-signal-regulated kinase  FXR  Farnesoid X Receptor  FGF15  fibroblast growth factor 15  GPCRs  G protein-coupled receptors  HDACs  histone deacetylases  IAld  indole-3- aldehyde  IBD  inflammatory bowel disease  IL  interleukin  LP  lamina propria  Mfs  macrophages  mROS  mitochondrial reactive oxygen species  MS  multiple sclerosis  NF-κB  nuclear factor-κB  Nod2  oligomerization domain 2  OMVs  outer membrane vesicles  Pglyrp3  peptidoglycan recognition protein 3  PAD  peptidylarginine deiminase  PD  periodontal disease  PSA  polysaccharide A  P. gingivalis  porphyromonas gingivalis  Treg  regulatory T cell  RA  rheumatoid arthritis  rRNA  ribosomal RNA  SFB  segmented filamentous bacterium  SCFAs  short-chain fatty acids  Slc5a8  solute carrier gene family 5a, member 8  SLE  systemic lupus erythematosus  Th17  T helper cell 17  TLR 4  Toll-like receptor 4  TGF-β  transforming growth factor–β  T1D  Type 1 diabetes  ILC3s  type 3 innate lymphoid cells  ZO-1  zona occludens-1  Autoimmune diseases  Gut microbes  Short-chain fatty acids  Bile acids  Fecal microbial transplantation  Probiotics
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