The gut ileal mucosal virome is disturbed in patients with Crohn’s disease and exacerbates intestinal inflammation in mice

Zhirui Cao, Dejun Fan, Yang Sun (), Ziyu Huang, Yue Li, Runping Su, Feng Zhang, Qing Li, Hongju Yang, Fen Zhang, Yinglei Miao, Ping Lan, Xiaojian Wu () and Tao Zuo ()
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Zhirui Cao: Ministry of Education
Dejun Fan: Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University
Yang Sun: The First Affiliated Hospital of Kunming Medical University
Ziyu Huang: Ministry of Education
Yue Li: Ministry of Education
Runping Su: Ministry of Education
Feng Zhang: Ministry of Education
Qing Li: Sun Yat-sen University
Hongju Yang: The First Affiliated Hospital of Kunming Medical University
Fen Zhang: Jinan University
Yinglei Miao: The First Affiliated Hospital of Kunming Medical University
Ping Lan: Ministry of Education
Xiaojian Wu: Ministry of Education
Tao Zuo: Ministry of Education

Nature Communications, 2024, vol. 15, issue 1, 1-22

Abstract: Abstract Gut bacteriome dysbiosis is known to be implicated in the pathogenesis of inflammatory bowel disease (IBD). Crohn’s disease (CD) is an IBD subtype with extensive mucosal inflammation, yet the mucosal virome, an empirical modulator of the bacteriome and mucosal immunity, remains largely unclear regarding its composition and role. Here, we exploited trans-cohort CD patients and healthy individuals to compositionally and functionally investigate the small bowel (terminal ileum) virome and bacteriome. The CD ileal virome was characterised by an under-representation of both lytic and temperate bacteriophages (especially those targeting bacterial pathogens), particularly in patients with flare-up. Meanwhile, the virome-bacteriome ecology in CD ileal mucosa was featured by a lack of Bifidobacterium- and Lachnospiraceae-led mutualistic interactions between bacteria and bacteriophages; surprisingly it was more pronounced in CD remission than flare-up, underlining the refractory and recurrent nature of mucosal inflammation in CD. Lastly, we substantiated that ileal virions from CD patients causally exacerbated intestinal inflammation in IBD mouse models, by reshaping a gut virome-bacteriome ecology preceding intestinal inflammation (microbial trigger) and augmenting microbial sensing/defence pathways in the intestine cells (host response). Altogether, our results highlight the significance of mucosal virome in CD pathogenesis and importance of mucosal virome restoration in CD therapeutics.

Date: 2024
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DOI: 10.1038/s41467-024-45794-y

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