Cross-kingdom metabolic interactions govern Candida albicans overgrowth and colitis progression

  • Cell Host Microbe. 2026 Jul 8;34(7):1445-1461.e7. doi: 10.1016/j.chom.2026.04.020.
Yilu Zhou  1 ,  Jinmei Ding  1 ,  Lijun Ning  1 ,  Xi Xu  1 ,  Lingyun Dou  1 ,  Jing Shen  2 ,  Baoqin Xuan  1 ,  Zhenyu Wang  1 ,  Yi Jiang  1 ,  Ying Zhao  1 ,  Yue Zhang  1 ,  Xiaowen Huang  1 ,  Muni Hu  1 ,  Yuqi Shao  1 ,  Lingxi Li  1 ,  Changbin Chen  3 ,  Min Li  4 ,  Jing-Yuan Fang  1 ,  Nan Shen  5 ,  Ning-Ning Liu  6 ,  Haoyan Chen  7 ,  Chunquan Sheng  8 ,  Jie Hong  9
Affiliations
  • 1. Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai 200001, China.
  • 2. Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), School of Pharmacy, Second Military Medical University (Naval Medical University), 325 Guohe Road, Shanghai 200433, China.
  • 3. Joint Laboratory for Biomedical Research and Pharmaceutical Innovation, Unit of Pathogenic Fungal Infection & Host Immunity, Key Laboratory of Molecular Virology and Immunology, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai 200032, China.
  • 4. Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
  • 5. Department of Infectious Disease, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Dongfang Rd. 1678, Shanghai 200127, China. Electronic address: [email protected].
  • 6. State Key Laboratory of Systems Medicine for Cancer, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: [email protected].
  • 7. Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai 200001, China. Electronic address: [email protected].
  • 8. Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), School of Pharmacy, Second Military Medical University (Naval Medical University), 325 Guohe Road, Shanghai 200433, China. Electronic address: [email protected].
  • 9. Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai 200001, China. Electronic address: [email protected].
PMID: 42208527 DOI: 10.1016/j.chom.2026.04.020
Abstract

Inflammatory bowel disease is shaped by complex microbial communities, yet the contribution of fungal-bacterial interactions to disease progression remains poorly defined. Here, we identify Cladosporium tenuissimum (C. tenuissimum) as a gut fungus with potent colitis-alleviating activity. Mechanistically, C. tenuissimum restrains Candida albicans (C. albicans) overgrowth through nutrient competition, particularly via the utilization and subsequent limitation of the amino acid ornithine. C. albicans can evade this suppression and potentiate intestinal inflammation through nutrient escape by preferentially exploiting specific Amino acids, such as threonine. We further reveal a bacterial-fungal metabolic axis in which threonine-producing Bacteroides fragilis facilitates C. albicans escape from gut microbiome-mediated Fungal control, thereby exacerbating colitis. Notably, dietary threonine restriction markedly attenuates C. albicans-driven colitis in mice. Together, our findings uncover a cross-kingdom metabolic network that determines C. albicans homeostasis and, in turn, governs intestinal inflammatory outcomes, offering new conceptual and therapeutic avenues for IBD.

Keywords
Bacteroides fragilis; Candida albicans; Cladosporium tenuissimum; cross-kingdom interaction; inflammatory bowel disease; nutrient competition; nutrient escape.
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