Weighted Gene Co-Expression Network Analysis Identifies a Functional Guild and Metabolite Cluster Mediating the Relationship between Mucosal Inflammation and Adherence to the Mediterranean Diet in Ulcerative Colitis

Abstract

Diet influences the pathogenesis and clinical course of inflammatory bowel disease (IBD). The Mediterranean diet (MD) is linked to reductions in inflammatory biomarkers and alterations in microbial taxa and metabolites associated with health. We aimed to identify features of the gut microbiome that mediate the relationship between the MD and fecal calprotectin (FCP) in ulcerative colitis (UC). Weighted gene co-expression network analysis (WGCNA) was used to identify modules of co-abundant microbial taxa and metabolites correlated with the MD and FCP. The features considered were gut microbial taxa, serum metabolites, dietary components, short-chain fatty acid and bile acid profiles in participants that experienced an increase (n = 13) or decrease in FCP (n = 16) over eight weeks. WGCNA revealed ten modules containing sixteen key features that acted as key mediators between the MD and FCP. Three taxa (Faecalibacterium prausnitzii, Dorea longicatena, Roseburia inulinivorans) and a cluster of four metabolites (benzyl alcohol, 3-hydroxyphenylacetate, 3-4-hydroxyphenylacetate and phenylacetate) demonstrated a strong mediating effect (ACME: −1.23, p = 0.004). This study identified a novel association between diet, inflammation and the gut microbiome, providing new insights into the underlying mechanisms of how a MD may influence IBD. See clinicaltrials.gov (NCT04474561).

The Impact of Dietary Interventions on the Microbiota in Inflammatory Bowel Disease: A Systematic Review

“…By contrast, Strauss et al . 50 trialled an 8-week MD diet with a special focus on reducing sulphur intake in UC patients, but found no significant differences in sulphur consumption and diet quality between the MD group and those consuming a habitual diet. A 4-week low-fat diet by Fritsch et al 40 led to a significant reduction in total fat [saturated and unsaturated] and omega 6:3 ratio in UC patients, and had a similar high adherence rate [87%] as the comparator iSAD group [85%].…”

“…The publication dates ranged from 2019 to 2023. Of the included studies, nine were experimental, of which six were RCTs, 39–43 , 49 , 50 and two were non-randomised interventions. 44 , 51 The remaining four studies were of cross-sectional design.…”

“…The dietary assessment and food analysis methods used to obtain information on dietary intake were highly variable. Three studies applied food diaries, 39 , 40 , 44 four studies used diet adherence questionnaires, 41 , 43 , 49 , 50 and five studies administered 24-h food recall questionnaires. 40 , 41 , 49–51 …”

“…It is worth noting that Strauss et al . 50 also examined changes in microbial taxa; however, the profiles were associated with changes in FC levels rather than relating to the MD diet.…”

“…Whereas a low FODMAP diet is recommended for managing individuals with IBS, the efficacy of this treatment in patients with quiescent IBD with concurrent IBS-like symptoms is controversial and is yet to established. Overall, four studies 41 , 44 , 49 , 50 featured the MD, which broadly appears to have positive associations with bacteria within the dominant Firmicutes phylum, such as Faecalibacterium , Clostridium, and Blautia , consistently found to be significantly depleted in the gut of IBD patients, 8 , 64 indicating that diet is imperative in shifting the intestinal microbial dysbiosis towards a balanced community.…”