Stool multi-omics for the study of host–microbe interactions in inflammatory bowel disease

Inflammatory Bowel Disease (IBD) is a chronic immune-mediated inflammatory disease of the gastrointestinal tract that is a growing public burden. Gut microbes and their interactions with hosts play a crucial role in disease pathogenesis and progression. These interactions are complex, spanning multiple physiological systems and data types, making comprehensive disease assessment difficult, and often overwhelming single-omic capabilities. Stool-based multi-omics is a promising approach for characterizing host-gut microbiome interactions using deep integration of technologies such as 16S rRNA sequencing, shotgun metagenomics, meta-transcriptomics, metabolomics, and metaproteomics. The wealth of information generated through multi-omic studies is poised to usher in advancements in IBD research and precision medicine. This review highlights historical and recent findings from stool-based muti-omic studies that have contributed to unraveling IBD’s complexity. Finally, we discuss common pitfalls, issues, and limitations, and how future pipelines should address them to standardize multi-omics in IBD research and beyond.