Parasutterella excrementihominis exacerbates experimental colitis and colitis-associated colorectal cancer via pathogenic NETosis activation

Background Parasutterella excrementihominis (P. excrementihominis), a Betaproteobacteria species enriched in ulcerative colitis (UC) patients, is implicated in chronic inflammation.

However, its mechanistic role in UC progression and colitis-associated colorectal cancer (CAC) remains unclear. Objective This study investigates the pathogenic role of P.

excrementihominis in UC and CAC, focusing on its induction of neutrophil extracellular traps (NETs) and underlying mechanisms. Design Clinical stool samples from UC patients and healthy controls were analysed for P.

excrementihominis abundance. Murine models of dextran sulphate sodium (DSS)-induced colitis and azoxymethane/DSS-induced CAC were used to evaluate bacterial pathogenicity.

RNA sequencing and metabolomic analyses were conducted on germ-free mice with monocolonisation, and in vitro cell experiments were carried out to elucidate the role of bacterial metabolites in NETosis. Results P.

excrementihominis was significantly enriched in UC patients and exacerbated colitis and CAC in mice by expanding colonic neutrophils and NETs formation. Metabolomic profiling revealed that P.

excrementihominis enhances the host's carbohydrate metabolic capacity, leading to increased production of succinic acid (Suc) and 6-hydroxyhexanoic acid (6-HHA).