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

  • Sanjoy Ghosh (a1), Erin Molcan (a1), Daniella DeCoffe (a1), Chaunbin Dai (a1) and Deanna L. Gibson (a1)...

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.

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*Corresponding author: D. L. Gibson, fax +1 250 807 8000, email
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1Walter J, Britton RA & Roos S (2011) Host–microbial symbiosis in the vertebrate gastrointestinal tract and the Lactobacillus reuteri paradigm. Proc Natl Acad Sci U S A 108, Suppl. 1, 46454652.
2Arumugam M, Raes J & Pelletier E (2011) Enterotypes of the human gut microbiome. Nature 473, 173180.
3Korecka A & Arulampalam V (2012) The gut microbiome: scourge, sentinel or spectator? J Oral Microbiol 4 (Epublication 21 February 2012).
4Ley R, Hamady M & Lozupone C (2008) Evolution of mammals and their gut microbes. Science 320, 16471651.
5Ley R, Turnbaugh P, Klein S, et al. (2006) Microbial ecology: human gut microbes assciated with obesity. Nature 444, 10221023.
6Sokol H, Seksik P, Furet JP, et al. (2009) Low counts of Faecalibacterium prausnitzii in colitis microbiota. Inflamm Bowel Dis 15, 11831189.
7Mariat D, Firmesse O, Levenez F, et al. (2009) The Firmicutes/Bacteroidetes ratio of the human microbiota changes with age. BMC Microbiol 9, 123.
8Wen L, Ley RE, Volchkov PY, et al. (2008) Innate immunity and intestinal microbiota in the development of type 1 diabetes. Nature 455, 11091113.
9Giongo A, Gano KA, Crabb DB, et al. (2011) Toward defining the autoimmune microbiome for type 1 diabetes. ISME J 5, 8291.
10Fava F, Gitau R, Griffin BA, et al. (2012) The type and quantity of dietary fat and carbohydrate alter faecal microbiome and short-chain fatty acid excretion in a metabolic syndrome ‘at-risk’ population. Int J Obes (Lond) (Epublication ahead of print version 13 March 2012).
11Caricilli A, Picardi P & de Abreu L (2011) Gut microbiota is a key modulatator of insulin resistance in TLR2 knockout mice. PLoS Biol 9, 121.
12Blasbalg TL, Hibbeln JR, Ramsden CE, et al. (2011) Changes in consumption of omega-3 and omega-6 fatty acids in the United States during the 20th century. Am J Clin Nutr 93, 950962.
13Tjonneland A, Overvad K, Bergmann MM, et al. (2009) Linoleic acid, a dietary n-6 polyunsaturated fatty acid, and the aetiology of ulcerative colitis: a nested case–control study within a European prospective cohort study. Gut 58, 16061611.
14Canete R, Gil-Campos M, Aguilera CM, et al. (2007) Development of insulin resistance and its relation to diet in the obese child. Eur J Nutr 46, 181187.
15Ramel A, Martinez A, Kiely M, et al. (2008) Beneficial effects of long-chain n-3 fatty acids included in an energy-restricted diet on insulin resistance in overweight and obese European young adults. Diabetologia 51, 12611268.
16Reaven P, Parthasarathy S, Grasse BJ, et al. (1991) Feasibility of using an oleate-rich diet to reduce the susceptibility of low-density lipoprotein to oxidative modification in humans. Am J Clin Nutr 54, 701706.
17Abbey M, Belling GB, Noakes M, et al. (1993) Oxidation of low-density lipoproteins: intraindividual variability and the effect of dietary linoleate supplementation. Am J Clin Nutr 57, 391398.
18Fernandez-Banares F, Esteve M, Navarro E, et al. (1996) Changes of the mucosal n-3 and n-6 fatty acid status occur early in the colorectal adenoma–carcinoma sequence. Gut 38, 254259.
19Nkondjock A, Shatenstein B, Maisonneuve P, et al. (2003) Assessment of risk associated with specific fatty acids and colorectal cancer among French-Canadians in Montreal: a case–control study. Int J Epidemiol 32, 200209.
20Nkondjock A, Krewski D, Johnson KC, et al. (2005) Specific fatty acid intake and the risk of pancreatic cancer in Canada. Br J Cancer 92, 971977.
21Belluzzi A, Brignola C, Campieri M, et al. (1996) Effect of an enteric-coated fish-oil preparation on relapses in Crohn's disease. N Engl J Med 334, 15571560.
22Innis SM & Jacobson K (2007) Dietary lipids in early development and intestinal inflammatory disease. Nutr Rev 65, S188S193.
23Dominguez-Bello MG, Blaser MJ, Ley RE, et al. (2011) Development of the human gastrointestinal microbiota and insights from high-throughput sequencing. Gastroenterology 140, 17131719.
24Biagi E, Hylund L, Candela M, et al. (2010) Through ageing, and beyond gut microbiota and inflammatory status in seniors and centenarians. PLoS One 5, e10667.
25Hill JO, Melanson EL & Wyatt HT (2000) Dietary fat intake and regulation of energy balance: implications for obesity. J Nutr 130, 284S288S.
26Portillo MP, Tueros AI, Perona JS, et al. (1999) Modifications induced by dietary lipid source in adipose tissue phospholipid fatty acids and their consequences in lipid mobilization. Br J Nutr 82, 319327.
27Kris-Etherton PM, Harris WS & Appel LJ (2002) Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation 106, 27472757.
28Gebauer SK, Psota TL, Harris WS, et al. (2006) n-3 Fatty acid dietary recommendations and food sources to achieve essentiality and cardiovascular benefits. Am J Clin Nutr 83, 1526S1535S.
29Hammer CT & Wills ED (1978) The role of lipid components of the diet in the regulation of the fatty acid composition of the rat liver endoplasmic reticulum and lipid peroxidation. Biochem J 174, 585593.
30Yuan YV & Kitts DD (2003) Dietary (n-3) fat and cholesterol alter tissue antioxidant enzymes and susceptibility to oxidation in SHR and WKY rats. J Nutr 133, 679688.
31Ghosh S, Dai C, Brown K, et al. (2011) Colonic microbiota alters host susceptibility to infectious colitis by modulating inflammation, redox status, and ion transporter gene expression. Am J Physiol Gastrointest Liver Physiol 301, G39G49.
32Wagner M, Amann R, Lemmer H, et al. (1993) Probing activated sludge with oligonucleotides specific for proteobacteria: inadequacy of culture-dependent methods for describing microbial community structure. Appl Environ Microbiol 59, 15201525.
33Meier H, Amann R, Ludwig W, et al. (1999) Specific oligonucleotide probes for in situ detection of a major group of gram-positive bacteria with low DNA G+C content. Syst Appl Microbiol 22, 186196.
34Klaus J, Spaniol U, Adler G, et al. (2009) Small intestinal bacterial overgrowth mimicking acute flare as a pitfall in patients with Crohn's disease. BMC Gastroenterol 9, 61.
35Murphy EF, Cotter PD, Healy S, et al. (2010) Composition and energy harvesting capacity of the gut microbiota: relationship to diet, obesity and time in mouse models. Gut 59, 16351642.
36 Statistics C (2006) Food Statistics 2005.
37Goyens PL, Spilker ME, Zock PL, et al. (2006) Conversion of alpha-linolenic acid in humans is influenced by the absolute amounts of alpha-linolenic acid and linoleic acid in the diet and not by their ratio. Am J Clin Nutr 84, 4453.
38Turnbaugh PJ, Ley RE, Mahowald MA, et al. (2006) An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444, 10271031.
39Tursi A, Brandimarte G, Giorgetti GM, et al. (2005) Assessment of small intestinal bacterial overgrowth in uncomplicated acute diverticulitis of the colon. World J Gastroenterol 11, 27732776.
40Pimentel M, Chow EJ & Lin HC (2000) Eradication of small intestinal bacterial overgrowth reduces symptoms of irritable bowel syndrome. Am J Gastroenterol 95, 35033506.
41Packey CD & Sartor RB (2009) Commensal bacteria, traditional and opportunistic pathogens, dysbiosis and bacterial killing in inflammatory bowel diseases. Curr Opin Infect Dis 22, 292301.
42Vijay-Kumar M, Aitken JD, Carvalho FA, et al. (2010) Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. Science 328, 228231.
43Cani PD, Delzenne NM, Amar J, et al. (2008) Role of gut microflora in the development of obesity and insulin resistance following high-fat diet feeding. Pathol Biol (Paris) 56, 305309.
44Turnbaugh PJ, Backhed F, Fulton L, et al. (2008) Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe 3, 213223.
45Tilg H, Moschen AR & Kaser A (2009) Obesity and the microbiota. Gastroenterology 136, 14761483.
46Atarashi K, Tanoue T, Shima T, et al. (2011) Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331, 337341.
47Geuking MB, Cahenzli J, Lawson MA, et al. (2011) Intestinal bacterial colonization induces mutualistic regulatory T cell responses. Immunity 34, 794806.
48Esterbauer H, Schaur RJ & Zollner H (1991) Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med 11, 81128.
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