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Though biologically benign, CP will damage the hypothalamus, inducing comorbidities such as obesity, metabolic syndrome, and cognitive impairments. The roles of gut microbiome and serum metabolome in CP\u2010associated hypothalamic comorbidities are aimed to be explored. Patients with CP are characterized by increased Shannon diversity, <jats:italic>Eubacterium<\/jats:italic>, <jats:italic>Clostridium<\/jats:italic>, and <jats:italic>Roseburia<\/jats:italic>, alongside decreased <jats:italic>Alistipes<\/jats:italic> and <jats:italic>Bacteroides<\/jats:italic>. CP\u2010enriched taxa are positively correlated with dyslipidemia and cognitive decline, while CP\u2010depleted taxa are negatively associated with fatty liver. Subsequent serum metabolomics identified notably up\u2010regulated purine metabolism, and integrative analysis indicated an association between altered microbiota and elevated hypoxanthine. Phenotypic study and multi\u2010omics analysis in the Rax\u2010CreER<jats:sup>T2<\/jats:sup>::Braf<jats:sup>V600E\/+<\/jats:sup>::Pten<jats:sup>Flox\/+<\/jats:sup> mouse model validated potential involvement of increased <jats:italic>Clostridium<\/jats:italic> and dysregulated purine metabolism in hypothalamic comorbidities. To further consolidate this, intervention experiments are performed and it is found that hypoxanthine co\u2010variated with the severity of hypothalamic comorbidities and abundance of <jats:italic>Clostridium<\/jats:italic>, and induced dysregulated purine metabolism along with redox imbalance in target organs (liver and brain cortex). Overall, the study demonstrated the potential of increased <jats:italic>Clostridium<\/jats:italic> and up\u2010regulated purine metabolism as signatures of CP\u2010associated hypothalamic\u2010comorbidities, and unveiled that elevated <jats:italic>Clostridium<\/jats:italic>, dysregulated purine metabolism, and redox imbalance may mediate the development and progression of CP\u2010associated hypothalamic\u2010comorbidities.<\/jats:p>","DOI":"10.1002\/advs.202400684","type":"journal-article","created":{"date-parts":[[2024,9,3]],"date-time":"2024-09-03T09:54:51Z","timestamp":1725357291000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Integrated Microbiome and Metabolome Analysis Reveals Hypothalamic\u2010Comorbidities Related Signatures in Craniopharyngioma"],"prefix":"10.1002","volume":"11","author":[{"given":"Ben","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Neurosurgery Huashan 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