The Relationship Between the Gut Microbiome, Genetic Mutations, and Anti-TNF Treatment in Inflammatory Bowel Disease

Abstract

Inflammatory bowel diseases (IBD) are thought to be autoimmune disorders in which the body’s immune system mistakenly attacks the intestinal tract and other parts of the body. Many of the genetic mutations associated with IBD are related to immune function, particularly interactions between the immune system and the microbiome.

The composition of the gut microbiome varies among individuals, with factors such as ethnicity, environmental conditions, age, diet, gender, and lifestyle contributing to its uniqueness. In patients with IBD, gut dysbiosis is characterized by decreased proportions of beneficial phyla, such as Bacteroidetes and Firmicutes, and increased proportions of Proteobacteria and Actinobacteria. Patients may also harbor potentially harmful bacteria, such as adherent-invasive E. coli (AIEC) and diffusely adherent E. coli (DAEC).

Genetic mutations associated with IBD, including mutations in NOD2 and ATG16L1, may impair immune defense, immune response regulation, autophagy, and bacterial recognition. These impairments can weaken the intestinal barrier and promote excessive inflammatory responses involving TH1 and TH17 cells and inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α).

Anti-TNF therapies reduce inflammation by preventing TNF-α from binding to its receptors. These treatments promote symptom relief, disease remission, and mucosal healing in patients with IBD. Anti-TNF treatments have also been associated with short-term changes in the intestinal microbiota of patients with CD. For example, treatment with adalimumab, an antibody that targets TNF-α, was associated with a significant reduction in the prevalence of E. coli after one and three months compared with levels measured before treatment. Firmicutes were also identified as the main phylogroup recovered after three months of treatment.

This research examines the relationships and interactions among genetic mutations, gut dysbiosis, TNF-α-mediated inflammation, and anti-TNF treatment in IBD. However, much more research is needed to fully understand IBD and the precise role of the microbiota in this disease.