Review highlights *E. coli*'s context-dependent shift from gut symbiont to **Inflammatory Bowel Disease** pathogen

Inflammatory Bowel Disease (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic, immune-mediated inflammatory condition driven by complex interactions among host immunity, genetic factors, and the gut microbiota. While E. coli is a common commensal, its remarkable genomic and metabolic plasticity allows it to transition into an opportunistic pathogen when mucosal integrity or immune surveillance is compromised. Understanding this shift is crucial for deciphering IBD pathophysiology and identifying novel therapeutic targets beyond current standard-of-care approaches, which often fall short in achieving sustained remission.

This comprehensive review synthesized current evidence on E. coli's multifaceted role in Inflammatory Bowel Disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC). The authors examined the mechanisms driving E. coli's transition from a beneficial commensal organism to a context-dependent pathobiont. The analysis focused on how horizontal acquisition of virulence determinants and antimicrobial resistance (AMR) genes contributes to the emergence of highly virulent and multidrug-resistant lineages. The review interpreted E. coli's contribution to IBD within the framework of mucosal inflammation and immune dysregulation, highlighting its dynamic interaction with the intestinal epithelium and host–microbe signaling networks.

The review elucidated that E. coli is an early and stable colonizer of the human gastrointestinal tract, typically functioning as a commensal that supports microbial homeostasis and host metabolism by producing essential metabolites. However, its significant genomic and metabolic plasticity enables a shift towards opportunistic pathogenicity, particularly when the host's mucosal integrity or immune surveillance is compromised. This context-dependent transition is frequently driven by the acquisition of virulence determinants and antimicrobial resistance (AMR) genes, leading to the emergence of more virulent and resistant strains. The authors emphasize that E. coli's contribution to Inflammatory Bowel Disease (IBD) emerges primarily under conditions of mucosal inflammation and immune dysregulation. This suggests that specific E. coli pathotypes act as intestinal pathobionts, contributing not only to disease persistence but also potentially to disease initiation. The review highlights the dynamic interface E. coli occupies with the epithelium, shaping host–microbe interactions through integrated metabolic and signaling networks. This re-evaluation of E. coli's role moves beyond a simple pathogen/commensal dichotomy to a more nuanced understanding of its conditional pathogenicity.

E. coli's role in Inflammatory Bowel Disease (IBD) is increasingly understood as a context-dependent pathobiont, contributing to both disease initiation and persistence, particularly under conditions of mucosal inflammation and immune dysregulation.