Combination of tart cherry and fish Oil exerted stronger attenuation of high-fat diet-induced gut dysbiosis and dysfunction in females than in males.

Background

Gut dysbiosis, disrupted intestinal barrier integrity, and elevated bacterial lipopolysaccharide levels are hallmarks of obesity-related metabolic dysfunctions. Fish oil (FO) and tart cherry (TC) have individually been shown to modulate gut microbiota dysbiosis and improve gut integrity.

Objective

We hypothesized that TC and FO, individually or in combination, would mitigate high-fat (HF) diet-induced dysbiosis and favorably modulate the expression of genes associated with intestinal barrier integrity.

Methods

Male and female C57BL/6J (BL6) and TALLYHO/Jng (TH) mice were fed low-fat (LF), HF, or HF supplemented with TC, FO, or TC+FO diets for 14 weeks from weaning. Cecal DNA was analyzed using 16S rRNA sequencing, and intestinal tissue was assessed for gut integrity gene expression.

Results

Supplementation with TC, FO, or TC+FO modulated gut microbial beta diversity in a strain- and sex-dependent manner. Combined TC+FO supplementation significantly increased Lachnospiraceae abundance (p < 0.03) and reduced Deferribacteraceae (p < 0.03), especially in females. With regards to intestinal barrier integrity, TC and FO supplementation, particularly in combination, attenuated HF-induced reductions in barrier integrity markers. TC+FO significantly upregulated Zo1, Ocln, and Muc2 expression in BL6 females (p < 0.05), while FO and TC+FO increased expression of these genes in TH females (p < 0.05), suggesting additive benefits.

Conclusions

Supplementation with TC and FO, particularly in combination, attenuated HF diet-induced gut dysbiosis and favorably modulated the expression of intestinal barrier-associated genes, suggesting potential protective effects against HF diet-induced gut dysfunction.