Inflammatory bowel disease (IBD) encompasses a heterogeneous group of chronic, immune-mediated inflammatory disorders that affect the gastrointestinal tract (1). Emerging evidence suggests that gut microbiota dysbiosis plays a pivotal role in the pathogenesis of IBD, contributing to both disease onset and progression (2). Among potential therapeutic interventions, krill oil (KO) has demonstrated potential efficacy in alleviating chemically induced acute colitis and parasite-driven infectious colitis in preclinical models (3; 4). However, it’s impact on gut microbiota remains poorly understood. This is the first study to examine the impacts of KO on gut microbiota composition and diversity in Winnie mice, a C57BL/6-based model of chronic colitis. Spontaneous colitis in these mice arises from a Muc2 gene mutation, resulting in epithelial defects that closely resemble the pathophysiology of human IBD. Furthermore, it evaluates the comparative effectiveness of KO and dexamethasone (DEX), and explores the possibility of synergistic interactions between these treatments. Winnie mice (Win/Win) were divided into four treatment groups (n = 10 per group) and fed a standard chow diet supplemented with either saline (intraperitoneal), 10% KO, 20 ng/g DEX (intraperitoneal), or a combination of 10% KO and 20 ng/g DEX. Heterozygous Winnie mice (Win/Wt) receiving saline served as the healthy control group. After 28 days of treatment, fecal samples were collected for DNA extraction and 16S rRNA sequencing on the Illumina MiSeq platform at the Australian Genome Research Facility (University of Queensland, Brisbane, Australia) to assess the composition of the gut microbiota. It was found that, while KO and DEX treatment alone showed some positive effects in restoring microbial composition, combined treatment with KO and DEX significantly modulated the gut microbiota profile in Win/Win mice. Beta diversity analysis revealed that KO+DEX most effectively restored the microbial community structure, similar to that of healthy controls (Win/Wt). This treatment also significantly increased the Firmicutes-to-Bacteroidetes ratio (68.35 ± 13.36%, p < 0.01) when compared to the Win/Win sham group mice (24.39 ± 5.74%), reaching levels comparable to those observed in Win/Wt mice (70.75 ± 7.86%). In addition, KO+DEX most effectively enhanced the relative abundance of beneficial bacterial genera, particularly the probiotic taxa, Bifidobacterium and Lactobacillus. These findings suggest that KO may serve as an adjunctive agent to DEX in the modulation of gut microbiota composition in a chronic colitis mouse model.
Keywords: Krill oil, Inflammatory bowel disease, Winnie mice, Gut microbiota
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