Abstract
Abstract
Background and Aims
As a microbiome/diet-derived vitamin, queuine (q) is a micronutrient that eukaryotes acquire from microbiota or diet. Vitamin q, the free base form of queuosine (Q), is used for Q-modification of transfer RNA (tRNA). Although tRNA-Q-modification in regulating eukaryotic cell physiology is recognized, the relationship between Q-tRNA-modification and the human microbiome in health and inflammatory bowel diseases (IBD) remains unknown. Which bacteria produce q and how the q-producing bacteria contributing to human health and IBD are not explored. Here, we hypothesize that disrupted microbial Q-biosynthesis contributes to the dysbiosis of human IBD. We performed comprehensive multi-omics integrative analyses using publicly available datasets. Specifically, we re-analyzed publicly available shotgun metagenomic, single-cell RNA sequencing (scRNA-seq), metabolic datasets, and completed meta-analysis.
Methods
To systematically investigate microbial Q-biosynthesis in healthy individuals and IBD patients, we performed a systematic secondary analysis by integrating 9 publicly available metagenomic datasets, 15 scRNA-seq datasets and one metabolic dataset published prior to 2026. We present a novel secondary bioinformatic reanalysis of sequence outputs mapped to the latest microbial taxonomy, functional pathways and microbial Q-related genes. Longitudinal study of shotgun metagenomics across the human lifespan (3146 samples) enabled taxonomic and functional profiling.
Results
We first identified key q-producing bacteria (e.g.,
Bacteroides
and
Alistipes
) in healthy populations. We then found that patients with IBD had significantly reducation of q-producing bacteria and a coordinated downregulation of the Q-related pathways, including Q, preQ
0
, de novo guanosine ribonucleotide biosynthesis and de novo guanosine deoxyribonucleotide biosynthesis pathways. This functional impairment was primarily driven by reduced contributions from
Bacteroides
,
Alistipes and Akkermansia
. The longitudinal stability of the q-producing bacteria community across the human lifespan (1638 samples). We observed a significant negative correlation between host age and the abundance of q-producing bacteria in patients with UC. Moreover, Queuine tRNA-ribosyltransferase 1 (QTRT1) expression in human intestinal epithelial cells was significantly reduced in patients with IBD compared to healthy controls.
Conclusions
Our study used multi-omics datasets to define a novel functional dysbiosis characterized by a reduction of microbial Q-biosynthesis in patients with IBD. Vitamin q and its tRNA modification is lesser-recognized in human IBD. Understanding the cellular and organismal mechanisms of this microbiome-dependent micronutrient will advance the prevention of IBD and improve the quality of life of patients with IBD.
What is already known on this topic?
Queuine, vitamin q, is a highly conserved hypermodified nucleoside micronutrition could only be acquired from microbiota or diet. It is used for modification of transfer RNA to protein transitional fidelity, but the specific microbial pathways evolved and the relationship with IBD are unclear.
What this study adds
This study identifies a novel functional dysbiosis in IBD patients characterized by the depletion of q-producing gut bacteria (e.g.,
Bacteroides
and
Alistipes
) and the downregulated microbial Q biosynthesis pathways, which correlates with host QTRT1 deficiency to potentially drive IBD pathogenesis.
How this study might affect research, practice or policy
1. Identifies the altered Q-biosynthesis pathway in human IBD. Establishes the “Microbial Q-synthesis-Host tRNA modification” axis as a novel mechanistic link, shifting human IBD microbiome research from taxonomic description to functional epitranscriptomics.
Overcomes the inherent biases of traditional meta-analyses through a unified secondary bioinformatic reanalysis, leveraging HMP unified metabolic analysis network 3 (HUMAnN3)-based modeling of 3,000+ samples, to reveal a universal breakdown of the microbial Q-biosynthetic supply chain across all IBD subtypes.
Recognize vitamin q as a critical gut-health micronutrient, influencing dietary guidelines and the regulation of functional medical foods for IBD management.