Letter: Exclusive Enteral Nutrition in Ulcerative Colitis—The Path Ahead Needs Careful Consideration. Authors' Reply

Abstract

We appreciate the interest of Melton et al. in our systematic review and meta-analysis on the use of exclusive enteral nutrition (EEN) in the management of ulcerative colitis (UC) in adults [1, 2].

As Melton et al. described, while preclinical studies suggest that elemental diets may improve intestinal inflammation in UC-like murine models, these effects have not been consistently replicated in human clinical trials. As in Crohn's disease (CD), the mechanistic efficacy of EEN in UC remains uncertain. Luminal factors thought to contribute to intestinal inflammation, such as increased hydrogen sulphide levels, reduced short-chain fatty acids (SCFA), and decreased microbiota diversity, have paradoxically been observed with EEN [3]. However, these effects may be mitigated by incorporating fibre-containing EEN formulas, which provide substrates necessary for microbial carbohydrate fermentation, thereby mitigating potentially deleterious sequelae of EEN [3].

It is an important observation that most associations between EEN and microbial alterations stem from studies on CD. However, contemporary studies of EEN in UC provide some insights. In patients with acute severe UC (ASUC), EEN combined with standard-of-care (SOC) corticosteroid therapy significantly increased the abundance of beneficial bacteria, including Faecalibacterium prausnitzii, a species associated with immunomodulatory activity and SCFA production in the gut [4, 5]. In contrast, the abundance of F. prausnitzii is reduced in patients with CD undergoing EEN [6]. These findings raise the possibility that EEN modulates the microbiota and metabolome differently in UC and CD; this should be further investigated in future studies.

As we highlighted, the current literature on EEN in UC is scarce and heterogeneous. Establishing a consistent EEN protocol, selecting clinically meaningful endpoints, defining their timeframe, and monitoring adherence are all crucial in designing future EEN trials. We identified significant heterogeneity across prospective and retrospective studies. In the treatment of ASUC, outcomes and time points should align with international consensus guidelines [7]. Moreover, given the availability of effective therapies in ASUC, EEN should only be considered an adjunct to SOC [7]. Exploring postoperative outcomes in patients receiving EEN before colectomy for ASUC would also provide valuable insights, as improved nutrition—reflected by significantly higher serum albumin levels in EEN-treated patients—may enhance post-surgical recovery.

Further investigation is also warranted to assess EEN's efficacy in mild UC, given that only one prospective trial has evaluated efficacy in this cohort [8]. In this setting, longer treatment durations (four or more weeks) could be explored. However, unlike CD, where corticosteroids are the mainstay therapy for mild-to-moderate disease [9], UC has well-tolerated and effective therapies such as mesalazine, which lack immunosuppressive properties and side effects. The primary appeal of EEN in UC may then be for patients seeking dietary therapy options or those requiring nutritional optimisation.

The role of EEN in UC remains uncertain. Further well-designed, high-quality prospective studies are needed. Given that treatment failure and colectomy rates remain high despite an expanding repertoire of advanced therapies, dietary interventions should not be overlooked and warrant further exploration.

The authors' declarations of personal and financial interests are unchanged from those in the original article [1].

Matthew K. W. Chu: conceptualization, writing – original draft, methodology, data curation, formal analysis, investigation. Alice S. Day: conceptualization, writing – review and editing, methodology, data curation, supervision. Lani Broad: data curation, investigation, writing – review and editing. Samuel P. Costello: methodology, writing – review and editing. Suzanne Edwards: formal analysis, writing – review and editing. Robert V. Bryant: conceptualization, methodology, supervision, writing – review and editing.

The authors declare no conflicts of interest.

This article is linked to Chu et al. papers. To view these articles, visit https://onlinelibrary.wiley.com/doi/10.1111/apt.18495 and https://doi.org/10.1111/apt.70091.