Crohn’s Disease: Evolution, Epigenetics, and the Emerging Role of Microbiome-Targeted Therapies Original paper

What was studied?

This review focuses on the evolution, epigenetics, and emerging role of microbiome-targeted therapies in Crohn’s disease (CD). Crohn’s disease is a chronic, immune-mediated inflammation of the gastrointestinal tract. Initially identified as a disease affecting only the distal ileum, it is now recognised as a heterogeneous condition with various phenotypes and systemic manifestations. The review explores the role of the microbiome in the disease, particularly in relation to disease pathogenesis, genetic susceptibility, and potential therapies. The study also examines how epigenetics and immunogenetics may influence disease progression and treatment responses, as well as the therapeutic implications of targeting the microbiome.

Who was studied?

The review discusses multiple studies on individuals with Crohn’s disease, focusing on both the clinical and molecular aspects of the disease. The studies involved patients with varying disease phenotypes, including those with inflammatory, fistulizing, and stricturing types of CD, and patients with extraintestinal manifestations such as arthritis and psoriasis. These patients were analysed to identify common genetic and environmental factors that contribute to disease onset and progression, with a particular emphasis on the role of microbiome dysbiosis. The findings are based on clinical observations, genetic studies, and microbiome analysis in these individuals.

Most important findings

One of the key insights from this review is the discovery that patients with Crohn’s disease exhibit a unique microbiome composition compared to healthy individuals. This dysbiosis, marked by reduced microbial diversity and an increase in pathogenic species such as E. coli, appears to play a critical role in promoting intestinal inflammation. Specifically, the presence of adherent-invasive E. coli (AIEC) in the intestines of CD patients is linked to heightened inflammation, as these bacteria are capable of invading intestinal epithelial cells and persisting within macrophages. The review also highlights the overlap between genes associated with CD and those related to mycobacterial diseases, suggesting that CD could be an adaptive response to environmental microbes. The review explores how epigenetic factors such as DNA methylation and histone modifications contribute to immune regulation in CD, influencing both the onset and progression of the disease. Finally, the review discusses the potential of microbiome-targeted therapies, such as probiotics and FMT, to manage CD.

Key implications

The findings underscore the critical need for personalised medicine in Crohn’s disease, particularly through microbiome-targeted therapies. The identification of microbial signatures associated with disease phenotypes offers the potential for more precise diagnostics and therapeutic interventions. Understanding the genetic and environmental factors that influence the microbiome could lead to better strategies for preventing disease onset and managing disease progression. Additionally, epigenetic insights into CD could guide the development of new therapies that address the underlying immune dysregulation in this condition. Ultimately, microbiome-targeted therapies could help mitigate the chronic inflammation that characterises CD and improve long-term outcomes for patients.