ZG16 impacts gut microbiota-associated intestinal inflammation and pulmonary mucosal function through bacterial metabolites.

Zymogen granule 16 (ZG16) is a secretory glycoprotein found in zymogen granules, which also plays an important role in colorectal inflammation and cancer. Herein, a ZG16 gene knock-out (ZG16 ^-/- ) mouse line was established and we found that ZG16 deletion damaged the intestinal mucosal barrier and gut microbiota, which resulted in low-level inflammation and further promoted the development of ulcerative colitis and inflammation-related colorectal cancer. Meanwhile, a metabolomics analysis on mouse feces showed that the metabolites significantly differed between ZG16 ^-/- and WT mice, which were important mediators of host-microbiota communication and may impact the pulmonary inflammation of mice. Indeed, ZG16 ^-/- mice showed more severe inflammation in a bronchial asthma model. Taken together, the results demonstrate that ZG16 plays a pivotal role in inhibiting inflammation and regulating immune responses in colorectum and lung of experimental animals, which may provide a better understanding of the underlying mechanism of human inflammatory diseases associated with ZG16.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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