A Mediterranean Diet Pattern Improves Intestinal Inflammation Concomitant with Reshaping of the Bacteriome in Ulcerative Colitis: A Randomised Controlled Trial

Abstract

Background and aims: Dietary patterns are important in managing ulcerative colitis [UC], given their influence on gut microbiome-host symbiosis and inflammation. We investigated whether the Mediterranean Diet Pattern [MDP] vs the Canadian Habitual Diet Pattern [CHD] would affect disease activity, inflammation, and the gut microbiome in patients with quiescent UC.

Methods: We performed a prospective, randomised, controlled trial in adults [65% female; median age 47 years] with quiescent UC in an outpatient setting from 2017 to 2021. Participants were randomised to an MDP [n = 15] or CHD [n = 13] for 12 weeks. Disease activity [Simple Clinical Colitis Activity Index] and faecal calprotectin [FC] were measured at baseline and week 12. Stool samples were analysed by 16S rRNA gene amplicon sequencing.

Results: The diet was well tolerated by the MDP group. At week 12, 75% [9/12] of participants in the CHD had an FC >100 μg/g, vs 20% [3/15] of participants in the MDP group. The MDP group had higher levels of total faecal short chain fatty acids [SCFAs] [p = 0.01], acetic acid [p = 0.03], and butyric acid [p = 0.03] compared with the CHD. Furthermore, the MDP induced alterations in microbial species associated with a protective role in colitis [Alistipes finegoldii and Flavonifractor plautii], as well as the production of SCFAs [Ruminococcus bromii].

Conclusions: An MDP induces gut microbiome alterations associated with the maintenance of clinical remission and reduced FC in patients with quiescent UC. The data support that the MDP is a sustainable diet pattern that could be recommended as a maintenance diet and adjunctive therapy for UC patients in clinical remission. ClinicalTrials.gov no: NCT0305371.

Keywords: Mediterranean diet; inflammation; microbiome; ulcerative colitis.

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Figure 1.

The MDP reduces faecal calprotectin and disease activity in UC patients. [A] Partial Mayo Score at baseline and week 12. [B] Disease activity response rates measured by the SCCAI at Week 12. [C] Faecal calprotectin values [ug/g] at baseline and week 12. [D] Faecal calprotectin response by diet, with response defined as a 50% in faecal calprotectin levels from baseline, maintenance of response defined as no change, and loss of response defined as an increase in baseline values. The Wilcoxon matched-pairs signed-rank test and Mann–Whitney test were performed for [B] and [F]. Fisher’s exact test was performed for [C], p <0.05. MDP, Mediterranean Diet Pattern; UC, ulcerative colitis; SCCAI, Simple Clinical Colitis Activity Index

Figure 2.

Faecal secretory IgA levels at baseline and Week 12. Faecal secretory IgA levels at baseline and week 12. The Wilcoxon matched-pairs signed-rank test and Mann–Whitney test were performed, p <0.05.

Figure 3.

The MDP reshapes the bacteriome in UC patients. [A] The compositional tensor factorization biplot demonstrates a significant separation of communities by diet over time. [B] The differential ranks generated by BIRDMAn highlight the taxa positively and negatively associated with the MDP compared with the CHD at week 12 [p = 0.00018]. MDP, Mediterranean Diet Pattern; UC, ulcerative colitis; CHD, Canadian Habitual Diet Pattern.

Figure 4.

The MDP is negatively associated with microbes carrying pathobiont traits. [A] A heatmap of predicted bacterial genera at baseline to Week 12 in the MDP and CHD; *indicates microbes carry potentially pathobiont traits. MDP, Mediterranean Diet Pattern; CHD, Canadian Habitual Diet Pattern.

Figure 5.

The MDP increases faecal short chain fatty acid [SCFA] production in UC patients. Faecal SCFAs measured at baseline and week 12 [umol/g]. [A] Total SCFAs. [B] Butyric acid. [C] Acetic acid. [D] Valeric acid. Wilcoxon matched-pairs signed-rank test and Mann–Whitney test, p <0.05. UC, ulcerative colitis.