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Deficiency of essential dietary n-3 PUFA disrupts the caecal microbiome and metabolome in mice

  • Ruairi C. Robertson (a1) (a2) (a3), Clara Seira Oriach (a3) (a4), Kiera Murphy (a2), Gerard M. Moloney (a5), John F. Cryan (a3) (a5), Timothy G. Dinan (a3) (a4), R. P. Ross (a6) and Catherine Stanton (a2) (a3) (a4)...

n-3 PUFA are lipids that play crucial roles in immune-regulation, cardio-protection and neurodevelopment. However, little is known about the role that these essential dietary fats play in modulating caecal microbiota composition and the subsequent production of functional metabolites. To investigate this, female C57BL/6 mice were assigned to one of three diets (control (CON), n-3 supplemented (n3+) or n-3 deficient (n3−)) during gestation, following which their male offspring were continued on the same diets for 12 weeks. Caecal content of mothers and offspring were collected for 16S sequencing and metabolic phenotyping. n3− male offspring displayed significantly less % fat mass than n3+ and CON. n-3 Status also induced a number of changes to gut microbiota composition such that n3− offspring had greater abundance of Tenericutes, Anaeroplasma and Coriobacteriaceae. Metabolomics analysis revealed an increase in caecal metabolites involved in energy metabolism in n3+ including α-ketoglutaric acid, malic acid and fumaric acid. n3− animals displayed significantly reduced acetate, butyrate and total caecal SCFA production. These results demonstrate that dietary n-3 PUFA regulate gut microbiota homoeostasis whereby n-3 deficiency may induce a state of disturbance. Further studies are warranted to examine whether these microbial and metabolic disturbances are causally related to changes in metabolic health outcomes.

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Corresponding author
* Corresponding author: Professor C. Stanton, email
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1. Claesson, MJ, Jeffery, IB, Conde, S, et al. (2012) Gut microbiota composition correlates with diet and health in the elderly. Nature 488, 178184.
2. O’Toole, PW (2012) Changes in the intestinal microbiota from adulthood through to old age. Clin Microbiol Infect 18, Suppl. 4, 4446.
3. Seira Oriach, C, Robertson, RC, Stanton, C, et al. (2016) Food for thought: the role of nutrition in the microbiota–gut–brain axis. Clin Nutr Exp 6, 2538.
4. Cryan, JF & Dinan, TG (2012) Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci 13, 701712.
5. Bäckhed, F, Roswall, J, Peng, Y, et al. (2015) Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe 17, 690703.
6. Cordain, L, Eaton, SB, Sebastian, A, et al. (2005) Origins and evolution of the Western diet: health implications for the 21st century. Am J Clin Nutr 81, 341354.
7. Simopoulos, AP (2002) The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomed Pharmacother 56, 365379.
8. Simopoulos, AP (1999) Essential fatty acids in health and chronic disease. Am J Clin Nutr 70, 3 Suppl., 560S569S.
9. Barker, DJ, Gluckman, PD, Godfrey, KM, et al. (1993) Fetal nutrition and cardiovascular disease in adult life. Lancet 341, 938941.
10. Lam, YY, Ha, CW, Campbell, CR, et al. (2012) Increased gut permeability and microbiota change associate with mesenteric fat inflammation and metabolic dysfunction in diet-induced obese mice. PLOS ONE 7, e34233.
11. Caesar, R, Tremaroli, V, Kovatcheva-Datchary, P, et al. (2015) Crosstalk between gut microbiota and dietary lipids aggravates WAT inflammation through TLR signaling. Cell Metab 22, 658668.
12. Kaliannan, K, Wang, B, Li, XY, et al. (2015) A host-microbiome interaction mediates the opposing effects of omega-6 and omega-3 fatty acids on metabolic endotoxemia. Sci Rep 5, 11276.
13. Patterson, E, O’ Doherty, RM, Murphy, EF, et al. (2014) Impact of dietary fatty acids on metabolic activity and host intestinal microbiota composition in C57BL/6J mice. Br J Nutr 111, 19051917.
14. Robertson, RC, Seira Oriach, C, Murphy, K, et al. (2017) Omega-3 polyunsaturated fatty acids critically regulate behaviour and gut microbiota development in adolescence and adulthood. Brain Behav Immun 59, 2137.
15. Pusceddu, MM, El Aidy, S, Crispie, F, et al. (2015) n-3 Polyunsaturated fatty acids (PUFAs) reverse the Impact of early-life stress on the gut microbiota. PLOS ONE 10, e0139721.
16. Andersen, AD, Mølbak, L, Thymann, T, et al. (2011) Dietary long-chain n-3 PUFA, gut microbiota and fat mass in early postnatal piglet development – exploring a potential interplay. Prostaglandins Leukot Essent Fatty Acids 85, 345351.
17. Andersen, AD, Mølbak, L, Michaelsen, KF, et al. (2011) Molecular fingerprints of the human fecal microbiota from 9 to 18 months old and the effect of fish oil supplementation. J Pediatr Gastroenterol Nutr 53, 303309.
18. Gibson, DL, Gill, SK, Brown, K, et al. (2015) Maternal exposure to fish oil primes offspring to harbor intestinal pathobionts associated with altered immune cell balance. Gut Microbes 6, 2432.
19. Myles, IA, Fontecilla, NM, Janelsins, BM, et al. (2013) Parental dietary fat intake alters offspring microbiome and immunity. J Immunol 191, 32003209.
20. Daniel, H, Moghaddas Gholami, A, Berry, D, et al. (2014) High-fat diet alters gut microbiota physiology in mice. ISME J 8, 295308.
21. Depner, CM, Traber, MG, Bobe, G, et al. (2013) A metabolomic analysis of omega-3 fatty acid-mediated attenuation of western diet-induced nonalcoholic steatohepatitis in LDLR-/- mice. PLOS ONE 8, e83756.
22. Marteau, P, Pochart, P, Doré, J, et al. (2001) Comparative study of bacterial groups within the human cecal and fecal microbiota. Appl Environ Microbiol 67, 49394942.
23. Folch, J, Lees, M & Sloane Stanley, GH (1957) A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 226, 497509.
24. Park, PW & Goins, RE (1994) In-situ preparation of fatty-acid methyl-esters for analysis of fatty-acid composition in foods. J Food Sci 59, 12621266.
25. Fouhy, F, Deane, J, Rea, MC, et al. (2015) The effects of freezing on faecal microbiota as determined using MiSeq sequencing and culture-based investigations. PLOS ONE 10, e0119355.
26. Magoč, T & Salzberg, SL (2011) FLASH: fast length adjustment of short reads to improve genome assemblies. Bioinformatics 27, 29572963.
27. Caporaso, JG, Kuczynski, J, Stombaugh, J, et al. (2010) QIIME allows analysis of high-throughput community sequencing data. Nat Methods 7, 335336.
28. Edgar, RC (2010) Search and clustering orders of magnitude faster than BLAST. Bioinformatics 26, 24602461.
29. Quast, C, Pruesse, E, Yilmaz, P, et al. (2013) The SILVA ribosomal RNA gene database project: improved data processing and web-based tools. Nucleic Acids Res 41, D590-6.
30. Lozupone, C, Lladser, ME, Knights, D, et al. (2011) UniFrac: an effective distance metric for microbial community comparison. ISME J 5, 169172.
31. Vázquez-Baeza, Y, Pirrung, M, Gonzalez, A, et al. (2013) EMPeror: a tool for visualizing high-throughput microbial community data. Gigascience 2, 16.
32. Smart, KF, Aggio, RB, Van Houtte, JR, et al. (2010) Analytical platform for metabolome analysis of microbial cells using methyl chloroformate derivatization followed by gas chromatography-mass spectrometry. Nat Protoc 5, 17091729.
33. Muhlhausler, BS, Miljkovic, D, Fong, L, et al. (2011) Maternal omega-3 supplementation increases fat mass in male and female rat offspring. Front Genet 2, 48.
34. Kaliannan, K, Wang, B, Li, XY, et al. (2016) Omega-3 fatty acids prevent early-life antibiotic exposure-induced gut microbiota dysbiosis and later-life obesity. Int J Obes (Lond) 40, 10391042.
35. Lecomte, V, Kaakoush, NO, Maloney, CA, et al. (2015) Changes in gut microbiota in rats fed a high fat diet correlate with obesity-associated metabolic parameters. PLOS ONE 10, e0126931.
36. Zhang, H, DiBaise, JK, Zuccolo, A, et al. (2009) Human gut microbiota in obesity and after gastric bypass. Proc Natl Acad Sci U S A 106, 23652370.
37. Koeth, RA, Wang, Z, Levison, BS, et al. (2013) Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med 19, 576585.
38. Niot, I, Poirier, H, Tran, TT, et al. (2009) Intestinal absorption of long-chain fatty acids: evidence and uncertainties. Prog Lipid Res 48, 101115.
39. Velagapudi, VR, Hezaveh, R, Reigstad, CS, et al. (2010) The gut microbiota modulates host energy and lipid metabolism in mice. J Lipid Res 51, 11011112.
40. Denou, E, Marcinko, K, Surette, MG, et al. (2016) High-intensity exercise training increases the diversity and metabolic capacity of the mouse distal gut microbiota during diet-induced obesity. Am J Physiol Endocrinol Metab 310, E982E993.
41. Williams, RE, Lenz, EM, Evans, JA, et al. (2005) A combined (1)H NMR and HPLC-MS-based metabonomic study of urine from obese (fa/fa) Zucker and normal Wistar-derived rats. J Pharm Biomed Anal 38, 465471.
42. Zhao, LC, Zhang, XD, Liao, SX, et al. (2010) A metabonomic comparison of urinary changes in Zucker and GK rats. J Biomed Biotechnol 2010, 431894.
43. Salek, RM, Maguire, ML, Bentley, E, et al. (2007) A metabolomic comparison of urinary changes in type 2 diabetes in mouse, rat, and human. Physiol Genomics 29, 99108.
44. Byrne, CS, Chambers, ES, Morrison, DJ, et al. (2015) The role of short chain fatty acids in appetite regulation and energy homeostasis. Int J Obes (Lond) 39, 13311338.
45. Hibberd, MC, Wu, M, Rodionov, DA, et al. (2017) The effects of micronutrient deficiencies on bacterial species from the human gut microbiota. Sci Transl Med 9, eaal4069.
46. Nguyen, TL, Vieira-Silva, S, Liston, A, et al. (2015) How informative is the mouse for human gut microbiota research? Dis Model Mech 8, 116.
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  • fatty acid methyl esters
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    fatty acid methyl esters
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    n-3 supplemented
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    tricarboxylic acid
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