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Review
. 2024 Jan 18;2(1):e100006.
doi: 10.1136/egastro-2023-100006. eCollection 2024 Jan.

Pathogenesis and precision medicine for predicting response in inflammatory bowel disease: advances and future directions

Robert D Little  1   2 , Thisun Jayawardana  3 , Sabrina Koentgen  3 , Fan Zhang  3 , Susan J Connor  4   5 , Alex Boussioutas  1   2 , Mark G Ward  1   2 , Peter R Gibson  2 , Miles P Sparrow  1   2 , Georgina L Hold  3
Affiliations
Review

Pathogenesis and precision medicine for predicting response in inflammatory bowel disease: advances and future directions

Robert D Little et al. eGastroenterology. .

Abstract

The pathogenesis of inflammatory bowel disease (IBD) is complex and multifactorial. Undertreated disease has substantial individual and societal consequences. Current patient classification and subsequent positioning of IBD therapy are based on crude, readily accessible clinical data. These broad parameters are unlikely to reflect underlying molecular profiles and may account for the observed heterogeneity in treatment response. Precision medicine offers identification and integration of molecular profiles into clinical decision-making. Despite several promising scientific and technological advances, the pathogenesis and targetable molecular drivers of IBD remain incompletely understood. Precision medicine therefore remains aspirational. This comprehensive narrative review describes our current understanding of IBD pathophysiology, highlights preliminary genetic, immunological and microbial predictors of treatment response and outlines the role of 'big data' and machine learning in the path towards precision medicine.

Keywords: Crohn's Disease; Gastrointestinal Microbiome; Inflammatory Bowel Diseases; Ulcerative Colitis.

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Conflict of interest statement

RDL has received educational support from Celltrion Healthcare and Janssen. SJC has received honoraria for advisory board participation, speaker fees, educational support and/or research support from AbbVie, Amgen, BMS, Celltrion, Chiesi, Dr Falk, Eli-Lilly, Ferring, Fresenius Kabi, GSK, Janssen, MSD, Novartis, Organon, Pfizer, Sandoz, Takeda, Agency for Clinical Innovation, Gastroenterological Society of Australia, Medical Research Future Fund, South Western Sydney Local Health District, Sydney Partnership for Health, Research and Enterprise (SPHERE) and The Leona M and Harry B Helmsley Charitable Trust. MGW has received educational grants or research support from Ferring, GESA and AbbVie; speaker fees from Janssen, AbbVie, Ferring, Takeda, Pfizer and MSD; and served on advisory boards for Janssen and AbbVie. PRG has served as a consultant or advisory board member for Anatara, Atmo Biosciences, Immunic Therapeutics, Novozymes, Novoviah, Intrinsic Medicine and Comvita; has received research grants for investigator‐driven studies from Atmo Biosciences; and is a shareholder with Atmo Biosciences. MPS has received educational grants or research support from Ferring, Orphan and Gilead; speaker fees from Janssen, AbbVie, Ferring, Takeda, Pfizer and Shire; and has served on advisory boards for Janssen, Takeda, Pfizer, Celgene, AbbVie, MSD, Emerge Health, Gilead and BMS. TJ, SK, FZ, AB and GLH have no relevant conflicts of interest to declare.

Figures

Figure 1
Figure 1. An illustration of the current imprecise approach to selecting IBD therapy. In this approach, patients are assessed using crude clinical, endoscopic and radiological evaluation. Subsequent categorisation results in inaccurate and heterogeneous patient phenotyping and thereby imprecise selection of IBD therapy. Created with BioRender.com. IBD, inflammatory bowel disease.
Figure 2
Figure 2. An illustration of the future of precision medicine and informed selection of IBD therapy. In this approach, patients are assessed using a combination of clinical and molecular profiling, incorporating genetic, immunological and microbial evaluation. Complex raw data are interpreted by omics-based network medicine, allowing accurate molecular profiling of patient groups and informed selection of a therapeutic agent, combination therapy, observation or novel dietary or microbial interventions. Created with BioRender.com. IBD, inflammatory bowel disease.
Figure 3
Figure 3. Major community and species-specific alterations in gut microbiota and metabolites associated with active inflammatory bowel disease (right) relative to healthy bowel (left). Created with BioRender.com. SCFA, short-chain fatty acid.
See this image and copyright information in PMC

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