Effects of different doses of omega-3 polyunsaturated fatty acids on gut microbiota and immunity

  • Xueliang Zhu State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan, China
  • Zhichao Bi Department of Microecology, School of Basic Medical Science, Dalian Medical University, Dalian, China
  • Chen Yang Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, Wuhan, China; Key Laboratory of Oilseeds Processing, Ministry of Agriculture and Rural Affairs, Wuhan, China
  • Yanhui Guo Department of Microecology, School of Basic Medical Science, Dalian Medical University, Dalian, China
  • Jieli Yuan Department of Microecology, School of Basic Medical Science, Dalian Medical University, Dalian, China
  • Longjie Li Department of Radiation Oncology, the First affiliated hospital of Dalian Medical University, Dalian, Liaoning, China
  • Yanjie Guo Department of Microecology, School of Basic Medical Science, Dalian Medical University, Dalian, China
Keywords: omega-3 PUFAs; microbiota; immunity; dose; ceftriaxone sodium


Background: Omega-3 polyunsaturated fatty acids (PUFAs) play beneficial roles in metabolism and health. Little is known about the effects of different doses of omega-3 PUFAs on gut microbiota.

Objective: In this study, we focus on the effects of different doses of omega-3 PUFAs on gut microbiota and immunity.

Design: BALB/c mice was first treated with ceftriaxone sodium for 7 days, and then they received saline or different doses of omega-3 PUFAs (30, 60 and 90 mg omega-3 PUFAs) via daily gavage for 21 days. Alterations of cecum microbiota; the tight junction proteins, zonula occludens 3 (ZO3) and occludin, in the ileal wall; serum lipopolysaccharide (LPS); Interleukin-10 (IL-10), interleukin-1β (IL-1β), and Tumour Necrosis Factor α (TNF-α) ; mucus SIgA levels were measured.

Results: Compared with the ceftriaxone sodium administration group, significant increases in bacterial richness and diversity were observed in the 60- and 90-mg omega-3 PUFA groups, while only a slight increase was observed in the 30-mg omega-3 PUFA group. A higher percentage of several genera, including LactobacillusHelicobacter, and Ruminococcus, and a lower percentage of BacteroidesClostridium, and Prevotella were observed in the 60- and 90-mg omega-3 PUFA groups when compared with those in the 30-mg group. The expression of ZO3 and occludin proteins increased in 60- and 90-mg omega-3 PUFA groups compared with the natural recovery group. The mucus SIgA and serum IL-10 levels were increased, and serum levels of LPS, IL-1β, and TNF-α were decreased in the 60- and 90-mg omega-3 PUFA groups when compared with those in the ceftriaxone sodium-treated group.

Conclusion: Different doses of omega-3 PUFAs have different therapeutic effects on the intestinal microbiota. The 60- and 90-mg omega-3 PUFA supplementation had better recovery effects on the gut microbiota and immunity than those of the 30 mg omega-3 PUFAs supplementation.


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  1. Gow RV, Hibbeln JR. Omega-3 fatty acid and nutrient deficits in adverse neurodevelopment and childhood behaviors. Child Adolesc Psychiatr Clin N Am 2014; 23(3): 555–90. doi: 10.1016/j.chc.2014.02.002

  2. Giannaccare G, Pellegrini M, Sebastiani S, Bernabei F, Roda M, Taroni L, et al. Efficacy of omega-3 fatty acid supplementation for treatment of dry eye disease: a meta-analysis of randomized clinical trials. Cornea 2019; 38(5): 565–73. doi: 10.1097/ICO.0000000000001884

  3. Scorletti E, Byrne CD. Omega-3 fatty acids, hepatic lipid metabolism, and nonalcoholic fatty liver disease. Annu Rev Nutr 2013; 33: 231–48. doi: 10.1146/annurev-nutr-071812-161230

  4. Deacon G, Kettle C, Hayes D, Dennis C, Tucci J. Omega 3 polyunsaturated fatty acids and the treatment of depression. Crit Rev Food Sci Nutr 2017; 57(1): 212–23. doi: 10.1080/10408398.2013.876959

  5. Watanabe Y, Tatsuno I. Omega-3 polyunsaturated fatty acids for cardiovascular diseases: present, past and future. Expert Rev Clin Pharmacol 2017; 10(8): 865–73. doi: 10.1080/17512433.2017.1333902

  6. Silva PS, Sperandio da Silva GM, de Souza AP, Cardoso CS, Fonseca CA, Brito PD, et al. Effects of omega-3 polyunsaturated fatty acid supplementation in patients with chronic chagasic cardiomyopathy: study protocol for a randomized controlled trial. Trials 2013; 14: 379. doi: 10.1186/1745-6215-14-379

  7. Fayh APT, Borges K, Cunha GS, Krause M, Rocha R, de Bittencourt PIH, et al. Effects of n-3 fatty acids and exercise on oxidative stress parameters in type 2 diabetic: a randomized clinical trial. J Int Soc Sports Nutr 2018; 15: 18. doi: 10.1186/s12970-018-0222-2

  8. Thota RN, Acharya SH, Garg ML. Curcumin and/or omega-3 polyunsaturated fatty acids supplementation reduces insulin resistance and blood lipids in individuals with high risk of type 2 diabetes: a randomised controlled trial. Lipids Health Dis 2019; 18(1): 31. doi: 10.1186/s12944-019-0967-x

  9. Tenenbaum A, Fisman EZ. Omega-3 polyunsaturated fatty acids supplementation in patients with diabetes and cardiovascular disease risk: does dose really matter? Cardiovasc Diabetol 2018; 17(1): 119. doi: 10.1186/s12933-018-0766-0

  10. Meyer BJ, Groot RHM. Effects of omega-3 long chain polyunsaturated fatty acid supplementation on cardiovascular mortality: the importance of the dose of DHA. Nutrients 2017; 9(12): 1305. doi: 10.3390/nu9121305

  11. Ni J, Wu GD, Albenberg L, Tomov VT. Gut microbiota and IBD: causation or correlation? Nat Rev Gastroenterol Hepatol 2017; 14(10): 573–84. doi: 10.1038/nrgastro.2017.88

  12. Zhu W, Gregory JC, Org E, Buffa JA, Gupta N, Wang Z, et al. Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk. Cell 2016; 165(1): 111–24. doi: 10.1016/j.cell.2016.02.011

  13. Tilg H, Moschen AR. Microbiota and diabetes: an evolving relationship. Gut 2014; 63(9): 1513–21. doi: 10.1136/gutjnl-2014-306928

  14. Chassaing B, Etienne-Mesmin L, Gewirtz AT. Microbiota-liver axis in hepatic disease. Hepatology 2014; 59(1): 328–39. doi: 10.1002/hep.26494

  15. Liu B, Lin W, Chen S, Xiang T, Yang Y, Yin Y, et al. Gut microbiota as a subjective measurement for auxiliary diagnosis of insomnia disorder. Front Microbiol 2019; 10: 1770. doi: 10.3389/fmicb.2019.01770

  16. Prochazkova P, Roubalova R, Dvorak J, Tlaskalova-Hogenova H, Cermakova M, Tomasova P, et al. Microbiota, microbial metabolites, and barrier function in a patient with anorexia nervosa after fecal microbiota transplantation. Microorganisms 2019; 7(9): 338. doi: 10.3390/microorganisms7090338

  17. Watson H, Mitra S, Croden FC, Taylor M, Wood HM, Perry SL, et al. A randomised trial of the effect of omega-3 polyunsaturated fatty acid supplements on the human intestinal microbiota. Gut 2018; 67(11): 1974–83. doi: 10.1136/gutjnl-2017-314968

  18. Gui L, Chen S, Wang H, Ruan M, Liu Y, Li N, et al. Omega-3 PUFAs alleviate high-fat diet induced circadian intestinal microbes dysbiosis. Mol Nutr Food Res 2019; 63(22): e1900492. doi: 10.1002/mnfr.201900492

  19. Costantini L, Molinari R, Farinon B, Merendino N. Impact of omega-3 fatty acids on the gut microbiota. Int J Mol Sci 2017; 18(12): 2645. doi: 10.3390/ijms18122645

  20. Gu S, Chen D, Zhang J-N, Lv X, Wang K, Duan L-P, et al. Bacterial community mapping of the mouse gastrointestinal tract. PLoS One 2013; 8(10): e74957. doi: 10.1371/journal.pone.0074957

  21. Donaldson GP, Lee SM, Mazmanian SK. Gut biogeography of the bacterial microbiota. Nat Rev Microbiol 2016; 14(1): 20–32. doi: 10.1038/nrmicro3552

  22. Guo Y, Yang X, Qi Y, Wen S, Liu Y, Tang S, et al. Long-term use of ceftriaxone sodium induced changes in gut microbiota and immune system. Sci Rep 2017; 7: 43035. doi: 10.1038/srep43035

  23. McCracken VJ, Lorenz RG. The gastrointestinal ecosystem: a precarious alliance among epithelium, immunity and microbiota. Cell Microbiol 2001; 3(1): 1–11. doi: 10.1046/j.1462-5822.2001.00090.x

  24. Lin S, Wang Z, Lam KL, Zeng S, Tan BK, Hu J. Role of intestinal microecology in the regulation of energy metabolism by dietary polyphenols and their metabolites. Food Nutr Res 2019; 63: 1518. doi: 10.29219/fnr.v63.1518

  25. Lozupone CA, Stombaugh JI, Gordon JI, Jansson JK, Knight R. Diversity, stability and resilience of the human gut microbiota. Nature 2012; 489(7415): 220–30. doi: 10.1038/nature11550

  26. Turnbaugh PJ, Backhed F, Fulton L, Gordon JI. Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe 2008; 3(4): 213–23. doi: 10.1016/j.chom.2008.02.015

  27. Willing BP, Dicksved J, Halfvarson J, Andersson AF, Lucio M, Zheng Z, et al. A pyrosequencing study in twins shows that gastrointestinal microbial profiles vary with inflammatory bowel disease phenotypes. Gastroenterology 2010; 139(6): 1844–54.e1. doi: 10.1053/j.gastro.2010.08.049

  28. Young VB, Schmidt TM. Antibiotic-associated diarrhea accompanied by large-scale alterations in the composition of the fecal microbiota. J Clin Microbiol 2004; 42(3): 1203–6. doi: 10.1128/jcm.42.3.1203-1206.2004

  29. Thursby E, Juge N. Introduction to the human gut microbiota. Biochem J 2017; 474(11): 1823–36. doi: 10.1042/BCJ20160510

  30. Cresci GA, Bawden E. Gut microbiome: what we do and don’t know. Nutr Clin Pract 2015; 30(6): 734–46. doi: 10.1177/0884533615609899

  31. Modi SR, Collins JJ, Relman DA. Antibiotics and the gut microbiota. J Clin Invest 2014; 124(10): 4212–8. doi: 10.1172/JCI72333

  32. Llewellyn SR, Britton GJ, Contijoch EJ, Vennaro OH, Mortha A, Colombel JF, et al. Interactions between diet and the intestinal microbiota alter intestinal permeability and colitis severity in mice. Gastroenterology 2018; 154(4): 1037–1046.e2. doi: 10.1053/j.gastro.2017.11.030

  33. Karl JP, Margolis LM, Madslien EH, Murphy NE, Castellani JW, Gundersen Y, et al. Changes in intestinal microbiota composition and metabolism coincide with increased intestinal permeability in young adults under prolonged physiological stress. Am J Physiol Gastrointest Liver Physiol 2017; 312(6): G559–71. doi: 10.1152/ajpgi.00066.2017

  34. Obrenovich MEM. Leaky gut, leaky brain? Microorganisms 2018; 6(4): 120. doi: 10.3390/microorganisms6040120

  35. Saad MJ, Santos A, Prada PO. Linking gut microbiota and inflammation to obesity and insulin resistance. Physiology 2016; 31(4): 283–93. doi: 10.1152/physiol.00041.2015

  36. Batra R, Suh MK, Carson JS, Dale MA, Meisinger TM, Fitzgerald M, et al. IL-1beta (interleukin-1beta) and TNF-alpha (tumor necrosis factor-alpha) impact abdominal aortic aneurysm formation by differential effects on macrophage polarization. Arterioscler Thromb Vasc Biol 2018; 38(2): 457–63. doi: 10.1161/ATVBAHA.117.310333

  37. Krishnan SM, Sobey CG, Latz E, Mansell A, Drummond GR. IL-1beta and IL-18: inflammatory markers or mediators of hypertension? Br J Pharmacol 2014; 171(24): 5589–602. doi: 10.1111/bph.12876

  38. Kuhn R, Lohler J, Rennick D, Rajewsky K, Muller W. Interleukin-10-deficient mice develop chronic enterocolitis. Cell 1993; 75(2): 263–74. doi: 10.1016/0092-8674(93)80068-p

  39. Begue B, Verdier J, Rieux-Laucat F, Goulet O, Morali A, Canioni D, et al. Defective IL10 signaling defining a subgroup of patients with inflammatory bowel disease. Am J Gastroenterol 2011; 106(8): 1544–55. doi: 10.1038/ajg.2011.112

How to Cite
Zhu X., Bi Z., Yang C., Guo Y., Yuan J., Li L., & Guo Y. (2021). Effects of different doses of omega-3 polyunsaturated fatty acids on gut microbiota and immunity. Food & Nutrition Research, 65. https://doi.org/10.29219/fnr.v65.6263
Original Articles