Disrupted microbial queuosine biosynthesis contributes to human inflammatory bowel disease via impaired tRNA modification

Background and Aims: Queuine (q) is a micronutrient that eukaryotes do not produce but acquire from microbiota or diet. Queuine is used for Queuosine (Q) modification of transfer RNA (tRNA), which is a critical epitranscriptomic mechanism that governs translational fidelity and efficiency. Interestingly, although tRNA-Q-modification in regulating eukaryotic cell physiology is recognized, the relationship between Q-modification and the human gut microbiome in health and inflammatory bowel diseases (IBD) remains unknown. Here, we hypothesize that disrupted microbial queuosine biosynthesis contributes to human IBD.Methods: To systematically investigate microbial queuosine biosynthesis in healthy individuals and patients with IBD, we performed comprehensive multi-omics integrative analyses using publicly available datasets. Specifically, we (1) evaluated host queuosine tRNA-ribosyltransferase (QTRT1) expression using a single-cell RNA sequencing (scRNA-seq) dataset GSE164985, (2) identified Q-associated bacterial taxa by a meta-analysis of nine public gut metagenomic datasets, including PRJEB7772, PRJEB7166, PRJNA313324, PRJNA276700, PRJNA385949, PRJNA422193, PRJNA450340, PRJNA400072, PRJNA389280 and PRJNA398089, and (3) quantified the genomic abundance of bacterial Q-biosynthesis functional pathways by comprehensive profiling of shotgun metagenomic data from the Inflammatory Bowel Disease Multi-omics Database (IBDMDB) cohort.Results: QTRT1 expression in intestinal epithelial cells was significantly reduced in single-cell RNA sequencing datasets from human IBD patients compared to healthy controls. Leveraging nine public gut metagenomic datasets, we identified that key Q-producing gut bacteria, e.g., Bacteroides and Alistipes, were significantly depleted in IBD patients. Compared to non-IBD controls, patients with Crohn's Disease (CD) and Ulcerative Colitis (UC) exhibited a significant and coordinated downregulation of the Q-related pathway at the genomic levels, including preQ0 biosynthesis, queuosine biosynthesis, de novo guanosine ribonucleotide biosynthesis, and de novo guanosine deoxyribonucleotide biosynthesis. This functional impairment was primarily driven by reduced contributions from Bacteroides (e.g., B. uniformis, B. eggerthii, B. coprocola and B. fluxus). Notably, pathways related to tRNA charging were concurrently diminished, suggesting disrupted microbial translational capacity in human IBD.Conclusions: Moving beyond descriptive compositional changes, our study defines a novel functional dysbiosis characterized by a reduction of microbial Q-biosynthesis in human IBD patients. These findings align with host QTRT1 deficiency observed in patients, suggesting a possible interplay between disrupted microbial Q-synthesis and host tRNA modification. This axis may represent a contributor to IBD pathogenesis and a potential target for diagnostic and/or therapeutic exploration. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.