Childhood Autoimmune Diseases (AID) are of special concern owing to high incidence, poor prognosis, and high disability rate. They are characterized by tissue damage resulting from the body's immune response to its own antigens, and include Kawasaki disease (KD), Henoch-Schonlein purpura (HSP), juvenile idiopathic arthritis (JIA), autoimmune uveitis, type 1 diabetes, multiple sclerosis (MS), lupus, glaucoma, Rheumatoid Arthritis (RA), and others.

In recent years, new etiologies and mechanisms of pathogenesis have been elucidated. Nevertheless, many efforts have failed to identify potentially clear pathogenesis. As research continues, the potential relationship between the gastrointestinal tract (GIT) and the protean functions of immunity has gained more attention. The GIT microbiota, a microbial community of trillions of microorganisms consisting of more than 5,000,000 genes, plays a vital role in the stimulation of immune-related angiogenesis and the occurrence of immune-mediated disorders. Immunologists have indicated that certain pathogens can mimic and produce antigens that are similar to host autoantigens while providing inflammatory signals for activating immune cells to trigger autoimmunity and causing the body to attack itself, which is known as “molecular mimicry”. It remains to be seen where the pathogens come from in otherwise healthy individuals. Two researchers found associated deposits of antibodies that can bind to glycosylates on the bacteria's surface in heart tissue of an 11-year-old boy who died of rheumatic fever, marking the GIT microbiota as invaders. Notably, studies have also shown that the afore-mentioned antigen mimics can stimulate immune cells into immune organs such as the eye, the central nervous system (CNS), etc. Related antigens specific to T cells and B cells can cross-react with bacterial antigens in the GIT, which develops into the so-called gut-microbiota-immune system cross-talk, further inducing the occurrence and development of AID. Based on these theories, probiotic applications have been increasingly regarded as therapeutic options, including fecal transplant, immune microenvironment infiltration, etc. However, the related therapies still have limitations and lack safety testing. Undoubtedly, more well-designed studies with a larger sample size are needed to support the feasibility of these treatments, and future studies will call for an integration of metagenomic, metabolomic, and gnotobiotic tests to further advance the study and understanding of the related reactions and relationships.

The aim of this Special Issue is to gather recent studies to aid in understanding the relevance of gut microbiota-immune system cross-talk in AID and thus develop new unconventional approaches to systems biology and immunology. Original research and review articles are welcome.

Potential topics include but are not limited to the following:

• The predisposing factors of AID that are linked to GIT microbiota
• Studies focusing on the primary nosogenesis of AID based on gut microbiota-immune system cross-talk
• Factors such as epigenetics affecting the GIT microbiota further inducing the occurrence and development of AID
• The studies of therapeutic effects to treat AID based on immune microenvironment infiltration and the internal environment of GIT microbiota
• Single-cell profiling of immune cells involved in AID
• The metabolites of GIT microbiota and AID
• Identification of novel molecular microbiota-immune-targets for personalized interventions derived from omics studies