Cao, Y. G. | bioRxiv Science

bioRxiv2026

Microbial-associated acylated putrescines as immunomodulatory molecules in inflammatory bowel diseases

The gut microbiota regulates intestinal immunity through metabolite production, yet most disease-associated metabolites remain functionally uncharacterized. In inflammatory bowel diseases (IBD), where the microbial metabolome is profoundly altered, we identify N-acyl putrescines as microbiome-associated metabolites enriched across two independent cohorts. N-oleoylputrescine (NOP) emerges as the primary immunomodulatory candidate, inducing robust transcriptional responses in dendritic cells and colonic organoids. Enterocloster species harboring nonribosomal peptide synthetase gene clusters synthesize NOP, confirmed by isotope-tracing in vitro and germ-free mouse colonization in vivo. NOP suppresses core IBD inflammatory pathways in mouse dendritic cells and human monocytes, reducing signatures of histologic inflammation and therapy non-response. NOP dampens inflammation in four colitis models, decreases myeloid cell NF-{kappa}B activation, and suppresses type 1 immune responses through a T cell-intrinsic mechanism. That NOP accumulates in IBD despite its anti-inflammatory properties reveals a holobiont defense strategy: the gut microbiota deploys immunomodulatory metabolites as a compensatory response to restore homeostasis.

immunology↗

bioRxiv2020

Diet Post-translationally Modifies The Gut Microbial Proteome To Modulate Renal Function

We identify a novel mechanism linking diet, gut microbial metabolism, and renal function. We found that a sulfur amino acid-based dietary intervention post-translationally modifies a microbial enzyme, blunting its uremic toxin-producing activity and alleviating chronic kidney disease (CKD) in a preclinical model. We also define a heretofore unknown role for the post-translational modification S-sulfhydration within the gut microbiome. This study provides a framework for understanding how diet can tune microbiota function via protein post-translational modification without altering microbial community composition to support healthy host physiology beyond the gut and specifically how a dietary modification can inhibit tryptophanase activity to ameliorate CKD progression. One Sentence SummaryWe found that diet post-translationally modifies the gut microbiota proteome to modulate kidney function.

microbiology↗