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  3. Integrated Microbiome and Metabolome Analysis Reveals Hypothalamic-Comorbidities Related Signatures in Craniopharyngioma

Integrated Microbiome and Metabolome Analysis Reveals Hypothalamic-Comorbidities Related Signatures in Craniopharyngioma

  • Adv Sci (Weinh). 2024 Oct;11(39):e2400684. doi: 10.1002/advs.202400684.
Ben Lin 1,  Zhen Ye 1,  Zhan Cao 2 3,  Zhao Ye 1,  Yifei Yu 4,  Weiliang Jiang 5 6,  Sichen Guo 7,  Vladimir Melnikov 4,  Peng Zhou 8,  Chenxing Ji 1,  Chengzhang Shi 1,  Zerui Wu 1,  Zhengyuan Chen 1,  Yihua Xu 1,  Qilin Zhang 1,  Zengyi Ma 1,  Nidan Qiao 1,  Long Chen 1,  Xuefei Shou 1,  Xiaoyun Cao 1,  Xiang Zhou 1,  Li Zhang 4,  Min He 4,  Yongfei Wang 1,  Hongying Ye 4,  Yiming Li 4,  Zhaoyun Zhang 4,  Meng Wang 4,  Renyuan Gao 2,  Yichao Zhang 1 9 10 11 12
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Huashan Hospital Fudan University, Shanghai, 200040, China.
  • 2 Department of General Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
  • 3 Institute of Gut Microbiota Research and Engineering Development, Shanghai Tenth People's Hospital Tongji University School of Medicine, Shanghai, 200072, China.
  • 4 Department of Endocrinology and Metabolism, Huashan Hospital Fudan University, Shanghai, 200040, China.
  • 5 Department of Gastroenterology, Shanghai General Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China.
  • 6 Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China.
  • 7 Shanghai Medical College, Fudan University, Shanghai, 200032, China.
  • 8 Department of Cardiology, Huashan Hospital Fudan University, Shanghai, 200040, China.
  • 9 National Center for Neurological Disorders, Shanghai, 200040, China.
  • 10 Shanghai Key Laboratory of Brain Function and Restoration and Neural Regeneration, Shanghai, 200040, China.
  • 11 Neurosurgical Institute of Fudan University Fudan University, Shanghai, 200040, China.
  • 12 Shanghai Clinical Medical Center of Neurosurgery, Shanghai, 200040, China.
PMID: 39225628 DOI: 10.1002/advs.202400684
Abstract

Craniopharyngioma (CP) is an intracranial tumor with high mortality and morbidity. 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-associated hypothalamic comorbidities are aimed to be explored. Patients with CP are characterized by increased Shannon diversity, Eubacterium, Clostridium, and Roseburia, alongside decreased Alistipes and Bacteroides. CP-enriched taxa are positively correlated with dyslipidemia and cognitive decline, while CP-depleted taxa are negatively associated with fatty liver. Subsequent serum metabolomics identified notably up-regulated purine metabolism, and integrative analysis indicated an association between altered microbiota and elevated hypoxanthine. Phenotypic study and multi-omics analysis in the Rax-CreERT2::BrafV600E/+::PtenFlox/+ mouse model validated potential involvement of increased Clostridium and dysregulated purine metabolism in hypothalamic comorbidities. To further consolidate this, intervention experiments are performed and it is found that hypoxanthine co-variated with the severity of hypothalamic comorbidities and abundance of Clostridium, and induced dysregulated purine metabolism along with redox imbalance in target organs (liver and brain cortex). Overall, the study demonstrated the potential of increased Clostridium and up-regulated purine metabolism as signatures of CP-associated hypothalamic-comorbidities, and unveiled that elevated Clostridium, dysregulated purine metabolism, and redox imbalance may mediate the development and progression of CP-associated hypothalamic-comorbidities.

Keywords

craniopharyngiomas; gut microbiota; hypothalamus‐pituitary axis; serum metabolome.

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