Authors
Huiye Liu, Mingxin Zhang, Weizhen Wu, Qingyun Deng, Xiaofang Li, Rongwei Ma, Lan Bai, Bing Huang
Published in
Microbiological research. Volume 315. Pages 128819. Nov 07, 2026. Epub Nov 07, 2026.
Abstract
Inflammatory bowel disease (IBD) is a chronic relapsing intestinal disorder characterized by mucosal inflammation, epithelial barrier disruption, and gut microbial dysbiosis. Excessive extracellular ATP (eATP) accumulates in inflamed intestinal tissues and amplifies immune activation through purinergic signaling, whereas adenosine generated from extracellular nucleotide metabolism exerts immunoregulatory effects. Here, we engineered the probiotic yeast Saccharomyces boulardii to sense eATP and convert it into adenosine through a CRISPR-engineered dual-enzyme pathway consisting of apyrase and 5'-nucleotidase. The engineered strain showed ATP-responsive pathway activation and efficiently generated adenosine from eATP, allowing extracellular nucleotide metabolism to be modulated in inflammatory settings. Oral administration of this strain significantly alleviated disease severity in acute dextran sulfate sodium (DSS)-induced colitis and showed beneficial effects in a repeated-DSS model, improved barrier-related epithelial features, reduced pro-inflammatory cytokine production, and supported mucosal recovery. Integrated microbiome and transcriptome analyses further showed partial restoration of gut microbial community structure, partial recovery of predicted microbial purine-related pathways, and attenuation of mucosal T-cell activation. Together, these findings indicate that engineered Saccharomyces boulardii can regulate extracellular purine metabolism in the inflamed gut and provide a microbial strategy for modulating intestinal inflammation.
PMID:
43033677
Bibliographic data and abstract were imported from PubMed on 15 Nov 2026.
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