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

Abstract

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.

Replacing saturated fatty acids with polyunsaturated fatty acids increases the abundance of Lachnospiraceae and is associated with reduced total cholesterol levels—a randomized controlled trial in healthy individuals

“…There were no correlations between gut bacteria and n6 fatty acids, but there was a negative correlation between EPA and Lachnospiraceae . Selmin et al found a reduction in Lachnospiraceae after a n6 high-fat diet in mice [ 30 ]. Others have shown a positive correlation between circulating levels of docosahexaenoic acid (DHA) (C22:6n3) and Lachnospiraceae [ 29 ] and an increase in several butyrate-producing bacteria in the Lachnospiraceae family after intervention with a n3 fatty acid-rich diet in adult males [ 27 ].…”

“…A correlation between omega-3 (n3) fatty acids and gut microbiota [ 27 , 28 ], including a positive correlation with bacteria of the Lachnospiraceae family [ 28 , 29 ], has been reported. In a recent study in mice, an omega-6 (n6) high-fat diet induced changes in gut microbiota, including a reduction in Lachnospiraceae [ 30 ]. However, only a few studies have investigated the effect of fat quality on gut microbiota and the impact on human metabolic regulation.…”

Porphyromonas gingivalis-Induced Cognitive Impairment Is Associated With Gut Dysbiosis, Neuroinflammation, and Glymphatic Dysfunction

“…Mucispirillum schaedleri is detected in a variety of mammals, and it is known to have low relative abundance of the intestinal microbiota in murine feces ( Herp et al., 2021 ). An increasing number of certain bacterial species have been associated with inflammatory conditions in the gut ( Selmin et al., 2021 ). Parabacteroides gordonii is one of the several gut bacteria with anti-inflammatory attributes ( Abais-Battad et al., 2021 ).…”

Adherence to the Mediterranean Diet Improves Fatty Acids Profile in Pediatric Patients with Idiopathic Nephrotic Syndrome

“…In effect, it has been established that its moderate intake is able to reduce total cholesterol and LDL concentrations [10] and to prevent the risk of development of cardiovascular disease [10,11]. However, the role of omega-6 metabolites is clearer, because they are involved in the inflammatory process in response to air pollution [12], and cause a shift in the microbiota, contributing to an increase of colonic inflammation [13]. Finally, a higher omega-6 dietary intake has been associated to an increase of pro inflammatory metabolites [14].…”