Diets Rich in n-6 PUFA Induce Intestinal Microbial Dysbiosis in Aged Mice

Br J Nutr. 2013 Aug 28;110(3):515-23. doi: 10.1017/S0007114512005326. Epub 2013 Jan 8.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteria / drug effects*
  • Bacteria / growth & development
  • Bacteria / immunology
  • Body Weight / drug effects
  • Diet / adverse effects*
  • Diet, High-Fat
  • Dietary Fats / adverse effects*
  • Dietary Fats / pharmacology
  • Dietary Fats / therapeutic use
  • Dietary Supplements
  • Fatty Acids, Omega-6 / adverse effects*
  • Female
  • Fish Oils / adverse effects
  • Fish Oils / therapeutic use
  • Ileum / drug effects*
  • Ileum / immunology
  • Ileum / microbiology
  • Inflammation / etiology*
  • Inflammation / immunology
  • Inflammation / microbiology
  • Intestinal Diseases / etiology*
  • Intestinal Diseases / immunology
  • Intestinal Diseases / microbiology
  • Lipid Peroxidation
  • Macrophages / immunology
  • Macrophages / metabolism
  • Metagenome / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Neutrophil Infiltration
  • Oxidative Stress
  • T-Lymphocytes, Regulatory / metabolism


  • Dietary Fats
  • Fatty Acids, Omega-6
  • Fish Oils