International journal of molecular sciences
Receptor-Side Neuroimmune Remodeling in IBD: Participant-Level Associations with Metabolite-Sensing Programs and Colorectal Neoplasia Context
By Hu H, Xu K, Yuan X and 2 others.
Abstract
Background
Microbial metabolite sensing and neuroimmune signaling are increasingly recognized as interacting components of the mucosal response in inflammatory bowel disease (IBD). However, their organization across individuals and the cellular compartments carrying the relevant receptor machinery remain incompletely understood. We investigated whether metabolite-sensing host programs covary with neuroimmune receptor-side mucosal states at the participant level and whether the corresponding receptor transcripts map to defined mucosal compartments.
Methods
HMP2 mucosal transcriptomes were analyzed at the participant level to evaluate prespecified relationships between metabolite-sensing and neuroimmune receptor-side host programs. Receptor-side neuroimmune remodeling was operationalized as cross-sectional participant-level host-program organization together with compartmental localization of the corresponding receptor transcripts, rather than longitudinal change or receptor activation. The stability and interpretation of these relationships were examined through diagnosis/inflammation adjustment, participant-grouped explanatory modeling, and tissue-composition sensitivity analyses. Complementary metabolomic, single-cell, UC, and colorectal-neoplasia datasets were used to examine synchronized metabolic associations, receptor-transcript localization, and the broader disease context of the identified mucosal programs. The microbiome, metabolomic, and transcriptomic datasets were obtained from multiple independent public cohorts.