Evidence of epigenetics in inflammatory bowel diseases

Inflammatory bowel diseases (IBDs) including Crohn’s disease (CD) and ulcerative colitis (UC) are characterised by a persistent relapsing-remitting inflammation in the gut. These are some of the most complex diseases that afflict the digestive tract, involving multiple factors, including genetics, environment, and gut microbiota. These diseases seem to be on the rise worldwide and can affect the quality of life of patients drastically. They may predispose to colorectal cancer, and treatment can be very costly. The etiology of these diseases is not well understood. Genetic factors, environmental factors, including diet, the gut microbiota, and epigenetic factors have been implicated with these diseases.

We edited a series on “Evidence of Epigenetics in Inflammatory Bowel Diseases”, combining four review articles and one original research article. The main purposes of this series are (I) to shed light onto potential links between epigenetic mechanisms and IBDs and to highlight new findings in this respect; (II) to explore progress in this field in pre-clinical models and in patients; and (III) to examine the role of environment in its broadest sense in IBD.

In the article by Rodrigues and collaborators titled: “The exposome-diet-epigenome axis in inflammatory bowel diseases—a narrative review” (1), the authors highlight the multifactorial nature of IBD. They point out that genetics does not explain the disease in its entire pathophysiology, emphasizing the need to investigate other pathways and factors, such as the epigenome, microbiome, diet, and exposome, to better understand IBD. They performed a thorough literature review to interpret the evidence on the association of environmental factors and endogenous factors in individuals with IBD and create a connection between these factors. They review known facts about genetic factors and IBD but mostly focus on the potential roles of environmental factors, summarised with the term ‘exposome’. This includes diet, gut microbiome, and diet effects on microbiome, including food additives. They write, “...epigenetic factors could mediate gene-environment interactions involved in resistant output and disease susceptibility, which makes epigenetics a key mechanism in IBD pathogenesis and other chronic and immune-mediated diseases”. They conclude their review by briefly outlining links between epigenetic mechanisms (DNA methylation, histone modifications) and IBD and focus on the role of noncoding RNA and microRNAs (miRNA) in this respect.

The topic of environmental influences is elaborated further by Zaltman and colleagues, who review what is published regarding the link between air pollution and IBD “Ambient air pollution and inflammatory bowel disease—a narrative review” (2). The authors conclude: “Besides conflicting and inconsistent results from previous studies and notable knowledge gaps, there is a plausible chance that the development of IBD can be affected by air pollution. Future prospective studies are required to gain comprehensive insight into this correlation.”

The review by Pereira and Varga-Weisz ‘Role of epigenetic mechanisms in inflammatory bowel disease’ (3) highlights the role of epigenetic mechanisms in IBD, focusing on recent work on epigenetic factors that have been identified by genetic means, SP140 and SETD2.

The theme of epigenetic mechanisms is expanded by the piece of Fernandes and Vinolo reviewing ‘Histone acylations as a mechanism for regulation of intestinal epithelial cells’ (4).

The review articles are complemented by a report from Dao and colleagues that introduces “A promising DNA methylation analysis pipeline for epigenetic studies and clinical implementation in inflammatory bowel disease” (5).

Therefore, this series deals with the main possible factors involved with the occurrence of IBD, which has been investigated in the last two decades. This knowledge may help to better understand the disease pathways and pursue background for further new treatments and control of intestinal inflammation in the future.

Acknowledgments

It was a real pleasure for us to coordinate the series and we wish to thank all the authors for their effort. Funding sources are acknowledged in each of our contributions.

Funding: This study was supported by National Council for Scientific and Technological Development (CNPq) (No. #302557/2021-0 to R.F.L.), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (No. #2019/16113-5 to P.V.W.) and National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) (No. NCW0010471 to P.V.W.).

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Digestive Medicine Research for the series “Evidence of Epigenetics in Inflammatory Bowel Diseases”. The article did not undergo external peer review.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://dmr.amegroups.com/article/view/10.21037/dmr-24-10/coif). The series “Evidence of Epigenetics in Inflammatory Bowel Diseases” was commissioned by the editorial office without any funding or sponsorship. R.F.L. and P.V.W. served as the unpaid Guest Editors of the series. R.F.L. received support from National Council for Scientific and Technological Development (CNPq) (No. #302557/2021-0). P.V.W. received grants and support for attending meetings or travel from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (No. #2019/16113-5) and National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) (No. NCW0010471). He also participates on NC3Rs grant panel. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Rodrigues BAG, Steigleder KM, Menta PLR, et al. The exposome-diet-epigenome axis in inflammatory bowel diseases—a narrative review. Dig Med Res 2024;7:6. [Crossref]
2. Zaltman C, do Espírito Santo PA, de Magalhães Costa MH. Ambient air pollution and inflammatory bowel disease—a narrative review. Dig Med Res 2024;7:13. [Crossref]
3. Pereira GV, Varga-Weisz P. Role of epigenetic mechanisms in inflammatory bowel disease. Dig Med Res 2024;7:8. [Crossref]
4. Fernandes MF, Vinolo MAR. Histone acylations as a mechanism for regulation of intestinal epithelial cells. Dig Med Res 2024;7:4. [Crossref]
5. Dao HV, Duong VC, Dao LV, et al. A promising DNA methylation analysis pipeline for epigenetic studies and clinical implementation in inflammatory bowel disease. Dig Med Res 2023;6:23. [Crossref]

Raquel Franco Leal

Patrick Varga-Weisz