Diets rich inn-6 PUFA induce intestinal microbial dysbiosis in aged mice

Abstract

Controversies have emerged regarding the beneficial v. detrimental effects of dietary n-6 PUFA. The alteration of the intestinal microbiota, a phenomenon termed dysbiosis, occurs during several chronic inflammatory diseases, but has not been well studied in an aged population. With present 'Western' diets predominantly composed of n-6 PUFA, we hypothesised that PUFA-rich diets cause intestinal dysbiosis in an aged population. C57BL/6 mice (aged 2 years) were fed a high-fat (40 % energy), isoenergetic and isonitrogenous diet composed of rapeseed oil, maize oil or maize oil supplemented with fish oil. We examined ileal microbiota using fluorescence in situ hybridisation and stained tissues by immunofluorescence for the presence of immune cells and oxidative stress. We observed that feeding high-fat diets rich in n-6 PUFA promoted bacterial overgrowth but depleted microbes from the Bacteroidetes and Firmicutes phyla. This corresponded with increased body mass and infiltration of macrophages and neutrophils. Fish oil supplementation (rich in long-chain n-3 PUFA like DHA and EPA) restored the microbiota and inflammatory cell infiltration and promoted regulatory T-cell recruitment. However, fish oil supplementation was associated with increased oxidative stress, evident by the increased presence of 4-hydroxynonenal, a product of lipid peroxidation. These results suggest that an n-6 PUFA-rich diet can cause dysbiosis and intestinal inflammation in aged mice. However, while fish oil supplementation on an n-6 PUFA diet reverses dysbiosis, the combination of n-6 and n-3 PUFA, like DHA/EPA, leads to increased oxidative stress, which could exacerbate gastrointestinal disorders in the elderly.

ω-3 polyunsaturated fatty acids ameliorate type 1 diabetes and autoimmunity

“…Moreover, oleic acid and linoleic acid diets have been reported to elevate the development of autoimmunity and intestinal inflammation in mice (61,62). Although the conclusions from these studies were generally consistent with our findings, one study also found the beneficial effect of an ω-6 PUFA-rich diet in alleviating inflammation in drug-induced mucosal damage (63).…”

Excess Linoleic Acid Increases Collagen I/III Ratio and “Stiffens” the Heart Muscle Following High Fat Diets

“…These results are supported by an earlier study, where a high fat, high sucrose diet induced LOX activity in mouse hearts by promoting LOX maturation, independent of its mRNA levels, via T cell activation (26). Although unknown in the heart, we recently demonstrated T cell recruitment in the gut with an LA-rich diet (10). In an earlier study, the increased dietary n-6 to n-3 PUFA ratio was shown to aggravate cross-linking of collagen in the bone dur- ing osteoarthritis (50).…”

“…However, sucrose content was similar between the two HF diets, and both the HF diets were isocaloric and isonitrogenous (Harlan Teklad, TD88232). The HF diets were supplemented with 20% w/w of either olive oil or corn oil (40% energy from fats) as described previously (10). The carbohydrate and protein contents were 39 and 19% energy, respectively.…”

Therapeutic Modulation of Gut Microbiota in Functional Bowel Disorders

“…43 A highfat diet alters the composition of the intestinal microbiota, and this promotes intestinal inflammation. [44][45][46][47] In one study, a high-fat diet induced increasing ileal tumor necrosis factor alpha mRNA only in conventionally raised, specific-pathogen-free mice and not in germfree mice. 46 It changes the behavior as well as the composition of the intestinal microbiota in genetically susceptible hosts, and promotes inflammation.…”