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Background : Concerns are emerging that a high-fat diet rich in n -6 PUFA ( n -6HFD) may alter gut microbiome and increase the risk of intestinal disorders. Research is needed to model the relationships between consumption of an n -6HFD starting at weaning and development of gut dysbiosis and colonic inflammation in adulthood. We used a C57BL/6J mouse model to compare the effects of exposure to a typical American Western diet (WD) providing 58.4%, 27.8%, and 13.7% energy (%E) from carbohydrates, fat, and protein, respectively, with those of an isocaloric and isoproteic soybean oil-rich n -6HFD providing 50%E and 35.9%E from total fat and carbohydrates, respectively on gut inflammation and microbiome profile. Methods : At weaning, male offspring were assigned to either the WD or n -6HFD through 10-16 weeks of age. The WD included fat exclusively from palm oil whereas the n -6HFD contained fat exclusively from soybean oil. We recorded changes in body weight, cyclooxygenase-2 (COX-2) expression, colon histopathology, and gut microbiome profile. Results : Compared to the WD, the n -6HFD increased plasma levels of n -6 fatty acids; colonic expression of COX-2; and the number of colonic inflammatory and hyperplastic lesions. At 16 weeks of age, the n -6HFD caused a marked reduction in the gut presence of Firmicutes , Clostridia , and Lachnospiraceae , and induced growth of Bacteroidetes and Deferribacteraceae . At the species level, the n -6HFD sustains the gut growth of proinflammatory Mucispirillum schaedleri and Lactobacillus murinus . Conclusions : An n -6HFD consumed from weaning to adulthood induces a shift in gut bacterial profile associated with colonic inflammation.

n-6 High Fat Diet Induces Gut Microbiome Dysbiosis and Colonic Inflammation