{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:01:00Z","timestamp":1790773260666,"version":"4.1.0"},"reference-count":200,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>As a core component of the human microecosystem, the dynamic balance of the composition and function of gut microbiota is essential to host health. In recent years, numerous studies have demonstrated that gut dysbiosis is not only associated with metabolic diseases and immune disorders but also plays a pivotal role in the pathogenesis of hereditary diseases. Ranging from chromosomal diseases (e.g., Down syndrome), monogenic diseases (e.g., cystic fibrosis, phenylketonuria, familial adenomatous polyposis, hereditary hemolytic anemia), mitochondrial diseases (e.g., Leber\u2019s hereditary optic neuropathy, mitochondrial encephalomyopathy) to polygenic hereditary diseases (e.g., inflammatory bowel disease, autism spectrum disorder, obesity and diabetes), gut microbiota can markedly alter the manifestation and severity of disease phenotypes by regulating host immune responses, metabolic pathways and gene expression. Nevertheless, the bidirectional interaction network between host genes and gut microbiota has not been fully elucidated. Most existing studies merely focus on correlation analysis, and in-depth exploration of causal mechanisms remains insufficient. This review elaborates on the mechanisms of gut microbiota in monogenic diseases and hereditary diseases with complex phenotypes. By integrating the latest advances in genomics, metabolomics and microbiomics, it discusses how gut dysbiosis affects disease progression via immune modulation, metabolite reprogramming and epigenetic modification. Meanwhile, this paper summarizes the current status and challenges of clinical translation of microbiota-targeted therapies, such as probiotics and fecal microbiota transplantation(FMT), in the treatment of hereditary diseases. This review aims to provide a microecological perspective for understanding the pathogenesis of hereditary diseases and offer theoretical support for personalized and precise intervention.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1908644","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T12:40:37Z","timestamp":1790772037000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Gut microbiota in genetic diseases: from Mendelian disorders to complex traits"],"prefix":"10.3389","volume":"17","author":[{"given":"Guanjun","family":"Chen","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of Guilin Medical University","place":["Guilin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junrong","family":"Li","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Guilin Medical University","place":["Guilin, 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