Shifting the Inflammatory Balance in Ulcerative Colitis Through Diet: A Mediterranean Diet Pattern is Associated with Improvements in Dysbiosis and Disease Activity

Diet continues to be studied as both a preventive and therapeutic modality in inflammatory bowel disease [IBD]. While recent evidence supports the role of dietary therapy for induction and maintenance of mild to moderate Crohn’s disease [CD], the evidence for diet in ulcerative colitis [UC] remains uncertain.¹ The intestinal microbiome is believed to play a key role in the pathogenesis of IBD and the impact of the environment on both gut health and mucosal immunity.^2,3 The Mediterranean diet pattern [MDP] is one high in fruits, vegetables, legumes, whole grains, nuts, seeds, and olive oil, and lower in fish, poultry, and dairy foods with minimal processed foods and red meat.⁴ In comparison with diets low in fibre and high in animal meat and processed foods, the MDP is being studied for its anti-inflammatory properties as well as its ability to promote favourable changes in gut microbiota composition.⁵

Dietary studies for induction and maintenance therapy of UC have focused predominantly on elimination of specific dietary components such as symptom-provoking foods, cow’s milk protein, gluten, or carrageenan-containing foods.^6,7 Most of these studies have shown only modest benefit along with a very low certainty of evidence.¹ Focusing on overall diet patterns, rather than eliminating specific food components, may be a more effective method of examining the impact of food on the microbiome, metabolome, and, subsequently, IBD. An anti-inflammatory diet showed favourable metabolic and microbial changes along with reduced faecal calprotectin [FC].⁸ A low-fat, high-fibre diet similarly reduced intestinal dysbiosis and decreased C-reactive protein [CRP].⁹ Another study evaluating the MDP, a type of anti-inflammatory low-fat, high-fibre diet, showed that patients with UC adherent to an MDP for 6 months showed improved disease activity, reduced inflammatory markers including CRP and FC, and improved quality of life.¹⁰ The numerous health benefits of the MDP and its potential for UC remain appealing, but rigorous randomized-controlled study data addressing the impact of the MDP on the microbiota and disease activity in this population are needed.

In this issue of the Journal of Crohn’s and Colitis, Haskey et al. report on an innovative, randomized-controlled trial investigating the impact of the MDP on intestinal inflammation and microbial diversity in patients with mild to moderate UC in clinical remission. Their study used a prospective, randomized, controlled design to assess the impact of the MDP on UC disease activity, levels of inflammation, as well as faecal short-chain fatty acids [SCFAs] and microbial species over a 12-week period. Fifteen adults were randomized to the MDP and 13 to the Canadian Habitual Diet pattern [CHD], a typical Western Diet pattern. The authors identified an improved simple clinical colitis activity index [SCCAI] score [40% vs 23%] and reduced FC < 100 µg/g [75% vs 20%] among the MDP cohort compared to the CHD group. Furthermore, they identified higher levels of total SCFAs, including acetic acid and butyric acid, and favourable alterations in microbial species associated with a protective role in colitis including higher levels of Alistipes finegoldii, Flavonifractor plautii, and Rumunicoccus bromii in the MD group compared to the CHD group. Furthermore, the MDP was associated with increased levels of secretory IgA, felt to play an important protective role in mucosal immunity.

The study is strengthened by its randomized, controlled design and longitudinal follow-up, assessing practical dietary patterns and their impact on symptom-reported disease activity as well as gut inflammation. Though most dietary studies have focused on CD and specific dietary components, this analysis addresses UC and studies diet in a manner presumably more consistent with real-world translation. This is due to its utilization of an MDP approach with a reasonable degree of proven adherence in addition to robust health benefits including reduction of inflammation as well as improved cardiovascular and metabolic disease profiles. Their study extends evidence that the MDP offers additional benefits in maintaining or improving disease activity and intestinal inflammation in UC. While these data do not demonstrate causality, following an MDP for 12 weeks was associated with favourable global improvements in disease activity, biochemical markers of inflammation, and microbiota composition shifts favouring anti-inflammatory characteristics and diminished abundance of pathobionts. The MDP is a sustainable, non-restrictive diet pattern which therefore shows promise as a complement to medical therapy for patients with UC.

Furthermore, there remains a paucity of data in IBD on how food may drive changes in the microbiome and the impact of such microbiota on important metabolites such as SCFAs. In contrast to studies examining the impact of dietary components on the microbiome, their study evaluated the levels of secretory IgA and metabolites such as SCFAs, both of which are believed to play a role in mucosal health and immunity. Patients with IBD typically have reduced levels of fibre-fermenting bacteria that produce SCFAs, such as acetate, propionate, and butyrate, which provide energy for colonocytes and maintain intestinal homeostasis.¹¹ Participants on an MDP were found to have significant increases from baseline in faecal IgA levels, as well as higher levels of protective taxa including Firmucutes subclusters Rumicoccus spp., Falonifractor spp., and the Bacteroidota genus Alistipes, as well as a decrease in the relative abundance of potentially pathogenic microbes. This focus on the influence of dietary patterns on gut inflammation, microbial species, and metabolites may serve to further uncover the underlying factors that drive UC.

Limitations of the study by Haskey et al. include a lack of endoscopic and histological samples to assess mucosal healing, which is the gold standard for disease response. However, biomarker data with FC and CRP, which are predictors of clinical outcomes in IBD, were included and demonstrated improvement with the MDP. Additionally, the relatively small sample size may limit generalizability and impact statistical analysis, particularly given that the habitual diet of two participants in the non-intervention arm resembled an MDP. Nevertheless, the robust study design and sufficient power to detect changes in inflammation and bacterial composition highlight the potential for the MDP to be further studied as an adjunctive therapy in preventing relapse for those in remission with UC. Importantly, it draws attention to the potential for the MDP to be further studied in larger clinical trials for both induction and maintenance of remission in mild to moderate UC.

Conflict of Interest

SNM: None. DJL: Consulting agreements with Abbvie, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Fresenius Kabi, Janssen, Palatin Technologies, Pfizer, Prometheus Biosciences, Takeda. Speaking fees: Abbvie, Janssen. Grant support: Abbvie, Boehringer Ingelheim, Janssen, Takeda.

Author Contributions

SNM and DJL: Writing and editing of the manuscript.