| Summary: | In this study we wanted to first describe the alterations in the gut microbiota that occur in response to diet-induced obesity in mice. Second, we examined whether dietary supplementation with a novel marine oil (Calanus® Oil from the copepod Calanus Finmarchicus), which has a strong anti-inflammatory as well as anti-obesogenic action, can prevent or limit such changes. For comparison, we also examined the effect of the GLP1-analog, exenatide, which is used for the treatment of diabetic patients. In this study, four groups of 5-6-week-old C57Bl/6J female mice (Charles River) were studied (5 mice per group). The first group served as the lean control group and was fed a normal chow diet containing 10% of energy from fat (NCD, no 58Y2, Test Diet; IPS Limited) for 20 weeks. The other groups were diet-induced obese by feeding a lard-based high-fat diet containing 46% of energy from fat (HFD, no 58V8, Test Diet; IPS Limited). The second group received the HFD for 20 weeks. The third and fourth group received the HFD for 12 weeks followed by 8 weeks of treatment. The third group received HFD supplemented with 2% (w/w) calanus oil, supplied by Calanus® AS, Tromsø, Norway, (HFD + Cal). The fourth group was fed HFD and treated with exenatide, 10µg/kg/day, via an mini-osmotic pumps implanted subcutaneously in the back of the animals (HFD + Ex). The addition of calanus oil was compensated for by removal of 2 g lard/100 g diet, making the total fat and energy content of the HFD and the HFD + Cal similar. Abstract Dietary supplementation withcalanus oil, a novel wax ester–rich marine oil, has been shown toreduce adiposity in high-fat diet (HFD)–induced obese mice. Current evidence suggests thatobesity and its comorbidities are intrinsicallylinked with unfavorable changes in the intestinalmicrobiome. Thus, in line with its antiobesity effect, we hypothesized that dietary supplemen-tation with calanus oil should counteract the obesity-related deleterious changes in the gutmicrobiota. Seven-week-old female C57bl/6J mice received an HFD for 12 weeks to induce obesityfollowed by 8-week supplementation with 2% calanus oil. For comparative reasons, anothergroup of mice was treated with exenatide, an antiobesogenic glucagon-like peptide-1 receptoragonist. Mice fed normal chow diet or nonsupplemented HFD for 20 weeks served as lean andobese controls, respectively. 16S rRNA gene sequencing was performed on fecal samples fromthe colon. HFD increased the abundance of theLactococcusandLeuconostocgenera relative tonormal chow diet, whereas abundances ofAllobaculumandOscillospirawere decreased.Supplementation with calanus oil led to an apparent overrepresentation ofLactobacillusandStreptococcusand underrepresentation ofBilophila. Exenatide prevented theHFD-induced increaseinLactococcusand caused a decreasein the abundance ofStreptococcuscompared to the HFDgroup. Thus, HFD altered the gut microbiota composition in an unhealthy direction by increasingthe abundance of proinflammatory genera whilereducing those considered health-promoting.These obesity-induced changes were antagonized by both calanus oil and exenatide
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