Dietary whey protein protects against Crohn’s disease by orchestrating cross-kingdom interaction between the gut phageome and bacteriome

作者：Runping Su, Weijie Wen, Yufeng Jin, Zhirui Cao, Zhiyang Feng, Jie Chen, Lu Yu, Guozhong Zhou, Chao Dong, Shanshan Gao, Xue Li, Hu Zhang, Kang Chao, Ping Lan, Xiaojian Wu, Anna Philips, Kun Li, Xiang Gao, Fen Zhang, Tao Zuo · 发表于：Gut · 年份：2025 · DOI：10.1136/gutjnl-2024-334516 · 被引用次数：15 · 研究领域：Bacteriophages and microbial interactions、Gut microbiota and health、Probiotics and Fermented Foods

Background The gut microbiome and diet are important factors in the pathogenesis and management of Crohn’s disease (CD). However, the role of the gut phageome under dietary influences is unknown. Objective We aim to explore the effect of diet on the gut phageome-bacteriome interaction linking to CD protection. Design We recruited CD patients and healthy subjects (n=140) and conducted a multiomics investigation, including paired ileal mucosa phageome and bacteriome profiling, dietary survey and phenome interrogation. We screened for the effect of diet on the gut phageome and bacteriome, as well as its epidemiological association with CD risks. The underlying mechanisms were explored in target phage-bacteria monocultures and cocultures in vitro and in two mouse models in vivo. Results On dietary screening in humans, whey protein (WP) consumption was found to profoundly impact the gut phageome and bacteriome (more pronounced on the phageome) and was associated with a lower CD risk. Indeed, the WP reshaped gut phageome can causally attenuate intestinal inflammation, as shown by faecal phageome versus bacteriome transplantation from WP-consuming versus WP-non-consuming mice to recipient mice. Mechanistically, WP induced phage (a newly isolated phage AkkZT003P herein) lysis of the mucin-foraging bacterium Akkermansia muciniphila , which unleashed the symbiotic bacterium Streptococcus thermophilus to counteract intestinal inflammation. Conclusion Our study charted the importance of ...