Improvement in Glucose Tolerance in Mice Fed a High‐fat Diet with a Low Omega‐6:Omega‐3 Ratio is Associated with Changes in Gut Microbiota

Abstract

Chronic consumption of a high‐fat diet (HFD) contributes to excessive weight gain and development of metabolic alterations, such as glucose intolerance. It also leads to changes in the gut microbiota, which recent findings suggest are associated with impaired glucose metabolism1. Although supplementing with omega‐3 polyunsaturated fatty acids (PUFAs) has been previously shown to affect glucose tolerance and the gut microbiota, the effect of increasing the amount of omega‐3 and lowering the ratio of omega‐6 to omega‐3 (O‐6:O‐3) PUFAs in a HFD has not been determined. Additionally, the association between improvement in glucose tolerance and changes in the gut microbiota in response to omega‐3 PUFAS needs to be investigated. In the present study, a HFD was modified to adjust the O‐6:O‐3 ratio to 1:1 by increasing the amount of omega‐3 PUFAs. Changes in glucose metabolism, gut microbiota and the association between these two outcomes were then investigated.Objectives(1) Determine the impact of reducing the dietary ratio of O‐6:O‐3 in HFDs on glucose tolerance. (2) Investigate the association between changes in the gut microbiome and glucose metabolism.MethodsC57BL/6J male mice were fed for 18 weeks either (a) standard chow (SD − 18% fat; (b) HFD (60% fat–10:1 O‐6:O‐3) or (c) omega‐3 enriched HFD diet (O3 −60% fat–1:1 O‐6:O‐3). After 16 weeks, they underwent glucose tolerance testing. Fecal samples were collected for microbiome analysis by 16S rRNA sequencing.ResultsSD mice gained less weight (13.1±0.4 g) when compared to HFD (26.0±1.1 g) and O3 mice (24.5±0.8 g). The area under the glucose tolerance curve (AUCglu) was lower in SD (44,106±1,081 mg/dL/hr) and O3 mice (45,542±2,873 mg/dL/hr) compared to HFD mice (66,193±1,947 mg/dL/hr; p<0.0001). The ratio of Firmicutes:Bacteroidetes in O3 mice (19.6±3.1) was lower than in HFD (36.6±5.3; p<0.0) and higher than in SD mice (2.3±0.5; p<0.01). Relative abundance of Firmicutes positively correlated with AUCglu (R=0.55; R2=0.316; p<0.0001). Relative abundance of Bacteroidetes negatively correlated with AUCglu (R=−0.51; R2=0.26; p<0.0001). The ratio of Firmicutes:Bacteroidetes positively correlated with AUCglu (R=0.59; R2=0.35; p<0.0001).DiscussionReducing the ratio of O‐6:O‐3 in a HFD from 10:1 to 1:1 prevented development of glucose intolerance regardless of excessive weight gain, and reduced the ratio of Firmicutes:Bacteroidetes in the gut microbiota. Additionally, correlation analyses show a strong association between changes in the microbiome and improvement in the glucose metabolism. Further analyses are needed to identify which specific family/genus in each phylum are driving this relationship.Support or Funding InformationCenter Alliance for Nutrition and Dietary Supplement ResearchThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.