Letter: Exclusive Enteral Nutrition in Ulcerative Colitis—The Path Ahead Needs Careful Consideration

Abstract

We read with interest the recent article by Chu et al. Meta-Analysis: Exclusive Enteral Nutrition in Adults With Ulcerative Colitis [1], which addresses the unresolved question of the efficacy of exclusive enteral nutrition (EEN) in the management of ulcerative colitis (UC).

Preclinical studies have previously demonstrated a significant reduction in colonic inflammation when using elemental diets in animal models mimicking UC [2]. However, these findings have seldom been replicated in human UC trials compared with Crohn's disease (CD), where EEN is an established therapy. These limitations may be due, in part, to existing studies combining patients with CD and UC, despite the significant pathophysiological differences between these conditions [3]. This heterogeneity can obscure disease-specific effects of EEN, particularly in UC. Furthermore, published studies have largely included cohorts with moderate-to-severe UC, acute severe UC or patients refractory to corticosteroids. These represent populations with a significant disease burden, and the efficacy of EEN on those with milder disease activity has not been clearly established. Additionally, there is significant heterogeneity in the duration of EEN (often 7–14 days of treatment in UC compared with 6–12 weeks in CD), follow-up and time to primary endpoints in these studies. Thus, it is unsurprising that positive findings have been sparsely seen in the published literature to date.

As noted by Chu et al. [1], faecal calprotectin appears to reduce after 7 days of EEN in UC. This raises the question as to whether we can expect meaningful therapeutic responses to EEN with a longer duration of therapy and follow-up when most modern IBD trials assess primary endpoints at 26 or 52 weeks. Furthermore, the adjunctive role of EEN to the expanding armamentarium of advanced therapies available for UC has not been fully established. Future studies should carefully consider the duration of EEN, appropriate timepoints to assess important outcomes, and evaluate a combination of clinical, biochemical, sonographic and endoscopic responses to gain a more nuanced understanding of the utility of EEN in UC.

The unique composition of EEN also warrants consideration in UC. Standard EEN formulas are fibre-free, which has known implications for the gut microbiota and has been demonstrated to promote a more dysbiotic microbial environment in Crohn's disease [4]. A deeper understanding of the mechanism of action of EEN, and therefore how it contributes to reduction in CD-related inflammation, would further progress our understanding of the role for EEN in UC. Resistant starch, fructooligosaccharide and non-starch polysaccharide have been shown to have some beneficial effects in previous studies [5], and therefore, mechanistic studies should consider fibre-free vs. fibre-containing formulas to potentially optimise the therapeutic benefit of EEN in UC.

In conclusion, we applaud the authors for advancing the conversation on EEN in UC. To truly understand its role, future studies must address these limitations by designing trials that stratify by disease type, evaluate longer durations of therapy, adopt appropriate endpoints and explore the impact of formula composition on treatment efficacy. Such efforts are critical to determine whether EEN has a therapeutic role in UC similarly to its established use in CD.

Sarah Melton: conceptualization, writing – original draft, writing – review and editing. Akhilesh Swaminathan: conceptualization, writing – original draft, writing – review and editing. Jessica Fitzpatrick: conceptualization, writing – original draft, 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://doi.org/10.1111/apt.18495 and https://doi.org/10.1111/apt.70121.