Pomegranate Extract Improves Colitis in IL‐10 Knockout Mice Fed a High Fat High Sucrose Diet

Abstract

Scope The study tests the hypothesis that dietary pomegranate extract (PomX) supplementation attenuates colitis in a Western diet feed IL‐10 deficient (IL‐10‐/‐) murine model. Methods and Results Four‐week‐old male IL‐10‐/‐ mice are randomly assigned to a high fat high sucrose (HFHS) diet or a HFHS diet supplement with 0.25% PomX for 8 weeks. PomX supplementation lead to significantly lower histological score for colitis (2.6 ± 0.5 vs 3.9 ± 1.0), lower spleen weight (0.11 ± 0.01 vs 0.15 ± 0.02), and lower circulating Interleukin 6(IL‐6) levels (15.8±2.2 vs 29.5±5.5) compared with HFHS fed controls. RNAseq analysis of colonic tissues showed 483 downregulated and 263 upregulated genes with PomX supplementation, which are mainly associated with inflammatory responses, defenses, and neutrophil degranulation. In addition, PomX treatment affects the cecal microbiome with increased alpha diversity, altered microbial composition, and increased levels of the tryptophan‐related microbial metabolite indole propionate. Conclusion The data demonstrate that dietary PomX supplementation ameliorated colitis and lowered inflammatory markers in HFHS fed IL‐10‐/‐ mice. These data support the anti‐inflammatory effects of dietary PomX supplementation for IBD and a potential mediating role of gut microbiome, suggesting the need for future clinical studies to explore the use of PomX dietary supplementation in IBD patients.

Anti-inflammatory activities of black raspberry seed ellagitannins and their structural effects on the stimulation of glucagon-like peptide-1 secretion and intestinal bitter taste receptors

“…42 In addition, it was reported that the supplementation of pomegranate extract, in which ellagitannins accounted for up to 40%, ameliorated colitis symptoms and downregulated circulating IL-6 levels in IL-10 knockout mice fed a high-fat and high-sucrose diet. 50 Also, pomegranate ellagitannin fractions were more effective in decreasing tissue damage in rats with colitis than pomegranate polysaccharide fractions. 51 Collectively, it can be assumed that BR ellagitannins may be attributed to the health benefits of BR in IBD.…”

Pomegranate (Punica granatum L.) and Its Rich Ellagitannins as Potential Inhibitors in Ulcerative Colitis

“…After 8 weeks of administration of PE to IL-10 knockout mice, the levels of LCN2 in the feces and plasma of the mice were detected. The results showed that PE could downregulate the level of LCN2 in the feces and plasma of IL-10 knockout mice and bring model group mice's LCN2 levels back to those of the control group after 8 weeks of administration [35].…”

“…IL-10 knockout mice spontaneously form UC at 8-12 weeks [84]. It was suggested that PE increased the abundance of Akkermansia muciniphila, which was negatively correlated with the histological score of colitis in the intestinal tract of IL-10 knockout mice and decreased the abundance of Paeniclostridium and Clostridium_sensu_stricto_1, which were positively correlated with the histological score of colitis [35]. The above results showed that PPE could regulate the composition and abundance of gut microbiota and alleviate the degree of colitis injury in IL-10 knockout mice.…”

Urolithin A-mediated augmentation of intestinal barrier function through elevated secretory mucin synthesis

“…Among polyphenols, ellagic acid possesses anti-inflammatory and antioxidant effects 6 . Dietary supplementation with pomegranate extract containing ellagic acid decreases oxidative stress in the colonic mucosa and reduces the colitis in an interleukin-10-deficient mouse model 7 , 8 . Recently, various polyphenols have been speculated to play specific roles in the gastrointestinal tract, particularly in relation to the intestinal bacteria in the colon 9 , 10 .…”