Multi-omics perspective: mechanisms of gastrointestinal injury repair

Abstract

In this review, we examine the significance of multi-omics technologies in understanding the plethora of intricate processes that activate gastrointestinal (GI) injury repair. Multi-omics, which includes genomics, transcriptomics, proteomics, and metabolomics, allows intricate mapping of cellular responses and molecular pathways involved in GI repair. We highlight the potential of multi-omics to discover previously unknown therapeutic targets or elucidate the molecular basis of the pathogenesis of GI. Furthermore, we explore the possibilities of integrating omics data to improve prediction models, and summarize the state-of-the-art technological developments and persisting obstacles that hinder the translation of multi-omics into clinical practice. Finally, innovative multi-omics approaches that can improve patient outcomes and advance therapeutic strategies in GI medicine are discussed.

Keywords: Gastroenterology; Gastrointestinal repair; Inflammatory bowel disease; Multi-omics.

Figure 1

Mucosal barriers in the gut. (a) In the small intestine, chemical barriers like antimicrobial peptides and regenerating islet-derived 3 (Reg3) family proteins secreted by Paneth cells separate the resident microflora and intestinal epithelial cells. (b) In the large intestine, MUC2 and Ly6/PLAUR domain containing 8, highly glycosylated proteins secreted by goblet cells and the absorptive epithelial cells, respectively, constitute the major chemical barrier. Adapted from [55] with permission. SFB, segmentous filamentous bacteria. SAA, serum amyloid A. ILC3, type3 innate lymphoid cells. NOD2, nucleotide-binding oligomerization domain-containing 2. TLR/MyD88, toll-like receptors/myeloid differentiation factor-88

Figure 2

Disruption in intestinal barrier function alters the intestinal microenvironment. Adapted from [36] with permission

Figure 3

Clinical genomics in the management of Mendelian disorder-associated IBD. Adapted from [14] with permission. HSCT, hematopoietic stem cell transplantation. XIAP, X-linked inhibitor of apoptosis protein. EPCAM, Epithelial cell adhesion molecule. TTC7A, tetratricopeptide repeat domain 7A. MVK, mevalonate kinase. NLRC4, NLR-family CARD-containing protein 4. CYBB, cytochrome B-245 beta chain. CYBA, cytochrome B-245 alpha chain. NCF2, neutrophil cytosolic factor 2. NCF4, neutrophil cytosolic factor 4. FOXP3, forkhead box p3. LRBA, LPS responsive beige-like anchor protein. CTLA4, cytotoxic T-lymphocyte associated protein 4

Figure 4

Microbiome-based therapies for IBD. Adapted from [7] with permission. AIEC, adhesive invasive E. coli