The interplay between immunogenetics and the human microbiota has emerged as a focal point in unraveling the complexities of autoimmune diseases. While HLA alleles are established as significant risk factors across multiple autoimmune disorders, recent evidence highlights that their impact is modulated by the composition and activity of the host’s microbiome. Ongoing research has demonstrated that certain microbes may provoke abnormal immune responses specifically in individuals who harbor susceptible HLA variants, suggesting a finely tuned dialog between host genetic background, microbial exposures, and immune function. Conversely, some commensal organisms may offer protection and help maintain immune tolerance, adding another layer of intricacy to disease susceptibility.
Despite substantial progress, the field continues to grapple with critical questions regarding why only some genetically at-risk individuals develop autoimmunity, and why similar environmental exposures do not uniformly yield the same outcomes.
Notably, it is now clear that the genesis and course of autoimmunity cannot be attributed to genetics or environment alone, but rather to a complex combination where gene–microbe interactions may be pivotal. Identifying the mechanisms and mediating factors in these interactions is a central challenge with high relevance for understanding disease heterogeneity, risk prediction, and novel therapeutic avenues.
This Research Topic aims to promote an integrated exploration of how HLA variants and microbiota interplay in the onset and progression of autoimmune diseases.
Key objectives include elucidating the molecular mechanisms of these interactions, clarifying causal relationships, and assessing how microbial composition may mediate genetic risk or confer resilience. By uniting work across immunology, genetics, microbiology, and clinical research, this collection aspires to clarify how variable combinations of genes and microbes govern susceptibility and resistance to autoimmunity.
To gather further insights in the intersection of host genetics, microbiota, and autoimmune disease, we welcome articles addressing, but not limited to, the following themes:
~ Mechanisms by which HLA alleles influence the composition and function of the microbiota on the modulation of autoimmune disorders ~ Microbial triggers of autoimmunity in genetically susceptible hosts ~ Protective roles of commensals and their interactions with the immune system ~ Microbiota-driven modulation of antigen presentation and immune reactivity ~ Longitudinal and comparative studies of HLA–microbiota interactions in different autoimmune disorders ~ Translational approaches and therapeutic implications targeting host–microbe crosstalk ~ Advances in models and technologies for studying gene–microbiome–immunity axes on autoimmune diseases
Appendix: We welcome the submission of original research articles, reviews, perspectives, and methodological studies relevant to these themes.
Article types and fees
This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:
Brief Research Report
Case Report
Clinical Trial
Conceptual Analysis
Editorial
FAIR² Data
FAIR² DATA Direct Submission
General Commentary
Hypothesis and Theory
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Article types
This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:
Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
