Munazza Yousuf

This pilot study investigated the effects of a reduced sulfur (RS) diet on the gut microbiome composition and fecal metabolome in individuals with remitted or active ulcerative colitis (UC). Thirteen participants maintained their habitual diet (control), while nine followed an RS diet for eight weeks (Wk8). Stool and plasma samples were collected at the baseline and Wk8. The sulfur intake decreased in the RS group (−28 g/1000 kcal) versus the control group (−1.7 g/1000 kcal; p < 0.001). The RS group exhibited a significant decrease in lipopolysaccharide-binding protein (−5280 ng/mL), while these levels increased in the control group (620 ng/mL; p < 0.05). The microbiome analysis showed an increased alpha diversity at Wk8 (p < 0.01), suggesting a microbial shift with a RS intake. The metabolic alterations indicated enhanced nitrogen disposal (increased uric acid, methyluric acid, N-acetyl-L-glutamate) and a higher energy demand (elevated ubiquinol and glucose-pyruvate). The RS diet increased beneficial microbes Collinsella stercoris, Asaccharobacter celatus, and Alistipes finegoldii, while decreasing pathobionts Eggerthella lenta and Romboutsia ilealis. Methyluric acid correlated positively with C. stercoris (β = 0.70) and negatively with E. lenta (β = −0.77) suggesting these microbes utilized this metabolite and influenced the microbiome composition. In conclusion, a RS diet promoted microbial diversity, metabolic adaptations, and reduced inflammation, highlighting its potential as a novel strategy for UC management.

Background and Objectives: The disruption of the intestinal epithelial barrier leads to increased intestinal permeability (IP), allowing endotoxins and pathogens to enter the bloodstream contributing to chronic inflammation. Western diets are associated with increased IP, while diets rich in polyphenols, fiber, and omega-3 fats are linked to decreased IP. The relationship between diet, disease activity, and IP in ulcerative colitis (UC) is poorly understood. We evaluated the effects of serum zonulin and lipopolysaccharide-binding protein (LBP) and their relationship to dietary factors in UC. Methods: A cross-sectional analysis was conducted on 37 UC participants who had baseline measures of dietary intake, disease activity and serum. Serum LBP and zonulin levels were measured by ELISA. Spearman’s rank correlations explored relationships between baseline IP, diet, and disease activity. Results: The median age was 35 years (29–47 years), 54% were male, and 76% were in clinical remission or had mild disease activity (partial Mayo score ≤ 4). LBP was significantly correlated (p < 0.05) with disease activity (partial Mayo score (r = 0.31), and positively correlated with total fat (r = 0.42) and refined grains (r = 0.35), but negatively correlated with fruit consumption (r = −0.50) and diet quality (r = −0.33). Zonulin was negatively correlated with protein (r = −0.39), niacin (r = −0.52) and vitamin B12 (r = −0.45) with a trend for significance (p = 0.06) with body mass index (r = 0.32). Conclusions: Baseline LBP levels were correlated with disease activity markers and dietary factors, suggesting that it could be a useful biomarker for assessing disease activity and diet quality in UC. Further trials are needed to confirm these findings.

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).