Effect of industrial trans-fatty acids-enriched diet on gut microbiota of C57BL/6 mice

Abstract

Purpose

Previous studies have shown that industrially originated trans-fatty acids (iTFAs) are associated with several chronic diseases, but the underlying mechanisms remain unknown. Because gut microbiota play a critical role in human health, diet competent induced gut microbiota dysbiosis may contributing to disease pathogenesis. Therefore, the present study examined the impact of iTFA on gut microbiota, help understanding the underling mechanism of iTFA-associated chronic diseases.

Methods

Forty male 8-week-old mice were divided into 4 groups and randomly assigned to diets containing soybean oil (non-iTFA) or partially hydrogenated soybean oil (iTFA). The intervention groups were: (1) low soybean oil (LS); (2) high soybean oil (HS); (3) low partially hydrogenated oil (LH) and (4) high partially hydrogenated oil (HH). The gut microbiota profiles were determined by 16S rRNA gene sequencing. Physiological parameters and the inflammatory status of the small intestine and other tissues were analyzed. Short-chain fatty acid levels in feces were measured using gas chromatography.

Results

The intake of iTFA increased the abundance of well-documented ‘harmful’ bacteria, such as Proteobacteria and Desulfovibrionaceae (P < 0.05), whereas it decreased relative abundance of ‘beneficial’ bacteria, such as Bacteroidetes, Lachnospiraceae, Bacteroidales S24-7 (P < 0.05). Surprisingly, the intake of iTFA increased the abundance of the probiotic Lactobacillaceae (P < 0.05). Additionally, the intake of iTFA induced increase of inflammatory parameters, as well as a numerical decrease of fecal butyric acid and valeric acid.

Conclusions

This study, to our knowledge, is the first to demonstrate that the consumption of iTFA resulted in a significant dysbiosis of gut microbiota, which may contribute to the development of chronic diseases associated with iTFA.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Abbreviations

TFA:

Trans-fatty acid

iTFA:

Industrial originated trans-fatty acids

SCFA:

Short-chain fatty acid

GC:

Gas chromatography

IBD:

Inflammatory bowel disease

SRB:

Sulfate-reducing bacteria

IL6:

Interleukin 6

TNF-α:

Tumor necrosis factor alpha

NAFLD:

Nonalcoholic fatty liver disease

NASH:

Nonalcoholic steatohepatitis

References

  1. 1.

    Sekirov I, Russell SL, Antunes LC, Finlay BB (2010) Gut microbiota in health and disease. Physiol Rev 90(3):859–904. https://doi.org/10.1152/physrev.00045.2009

    CAS  Article  Google Scholar 

  2. 2.

    Round JL, Mazmanian SK (2009) The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol 9(5):313–323. https://doi.org/10.1038/nri2515

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  3. 3.

    Cani PD, Bibiloni R, Knauf C, Waget A, Neyrinck AM, Delzenne NM, Burcelin R (2008) Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 57(6):1470–1481. https://doi.org/10.2337/db07-1403

    CAS  Article  Google Scholar 

  4. 4.

    Brennan CA, Garrett WS (2016) Gut microbiota, inflammation, and colorectal cancer. Annu Rev Microbiol 70:395–411. https://doi.org/10.1146/annurev-micro-102215-095513

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Velagapudi VR, Hezaveh R, Reigstad CS, Gopalacharyulu P, Yetukuri L, Islam S, Felin J, Perkins R, Boren J, Oresic M, Backhed F (2010) The gut microbiota modulates host energy and lipid metabolism in mice. J Lipid Res 51(5):1101–1112. https://doi.org/10.1194/jlr.M002774

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Macfarlane GT, Blackett KL, Nakayama T, Steed H, Macfarlane S (2009) The gut microbiota in inflammatory bowel disease. Curr Pharm Des 15(13):1528–1536

    CAS  Article  Google Scholar 

  7. 7.

    De Filippo C, Cavalieri D, Di Paola M, Ramazzotti M, Poullet JB, Massart S, Collini S, Pieraccini G, Lionetti P (2010) Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci USA 107(33):14691–14696. https://doi.org/10.1073/pnas.1005963107

    Article  PubMed  Google Scholar 

  8. 8.

    Daniel H, Gholami AM, Berry D, Desmarchelier C, Hahne H, Loh G, Mondot S, Lepage P, Rothballer M, Walker A, Bohm C, Wenning M, Wagner M, Blaut M, Schmitt-Kopplin P, Kuster B, Haller D, Clavel T (2014) High-fat diet alters gut microbiota physiology in mice. ISME J 8(2):295–308. https://doi.org/10.1038/ismej.2013.155

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Zhang C, Zhang M, Pang X, Zhao Y, Wang L, Zhao L (2012) Structural resilience of the gut microbiota in adult mice under high-fat dietary perturbations. ISME J 6(10):1848–1857. https://doi.org/10.1038/ismej.2012.27

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Etxeberria U, Fernandez-Quintela A, Milagro FI, Aguirre L, Martinez JA, Portillo MP (2013) Impact of polyphenols and polyphenol-rich dietary sources on gut microbiota composition. J Agric Food Chem 61(40):9517–9533. https://doi.org/10.1021/jf402506c

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Chassaing B, Koren O, Goodrich JK, Poole AC, Srinivasan S, Ley RE, Gewirtz AT (2015) Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome. Nature 519(7541):92–96. https://doi.org/10.1038/nature14232

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Hildebrandt MA, Hoffmann C, Sherrill-Mix SA, Keilbaugh SA, Hamady M, Chen YY, Knight R, Ahima RS, Bushman F, Wu GD (2009) High-fat diet determines the composition of the murine gut microbiome independently of obesity. Gastroenterology 137(5):1716–1724. https://doi.org/10.1053/j.gastro.2009.08.042

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Yu HN, Zhu J, Pan WS, Shen SR, Shan WG, Das UN (2014) Effects of fish oil with a high content of n-3 polyunsaturated fatty acids on mouse gut microbiota. Arch Med Res 45(3):195–202. https://doi.org/10.1016/j.arcmed.2014.03.008

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Micha R, Mozaffarian D (2009) Trans fatty acids: effects on metabolic syndrome, heart disease and diabetes. Nat Rev Endocrinol 5(6):335–344. https://doi.org/10.1038/nrendo.2009.79

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Okada Y, Tsuzuki Y, Ueda T, Hozumi H, Sato S, Hokari R, Kurihara C, Watanabe C, Tomita K, Komoto S, Kawaguchi A, Nagao S, Miura S (2013) Trans fatty acids in diets act as a precipitating factor for gut inflammation? J Gastroenterol Hepatol 28(Suppl 4):29–32. https://doi.org/10.1111/jgh.12270

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Smith BK, Robinson LE, Nam R, Ma DW (2009) Trans-fatty acids and cancer: a mini-review. Br J Nutr 102(9):1254–1266. https://doi.org/10.1017/S0007114509991437

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Wilczek MM, Olszewski R, Krupienicz A (2017) Trans-fatty acids and cardiovascular disease: urgent need for legislation. Cardiology 138(4):254–258. https://doi.org/10.1159/000479956

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Ley RE, Turnbaugh PJ, Klein S, Gordon JI (2006) Microbial ecology: human gut microbes associated with obesity. Nature 444(7122):1022–1023. https://doi.org/10.1038/4441022a

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Kuczynski J, Stombaugh J, Walters WA, Gonzalez A, Caporaso JG, Knight R (2012) Using QIIME to analyze 16S rRNA gene sequences from microbial communities. Curr Protoc Microbiol. https://doi.org/10.1002/9780471729259.mc01e05s27 (Chap. 1:Unit 1E 5)

    Article  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Quast C, Pruesse E, Yilmaz P, Gerken J, Schweer T, Yarza P, Peplies J, Glockner FO (2013) The SILVA ribosomal RNA gene database project: improved data processing and web-based tools. Nucleic Acids Res 41(Database issue):D590–D596. https://doi.org/10.1093/nar/gks1219

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Wu Q, Shah NP (2014) Effects of elaidic acid, a predominant industrial trans fatty acid, on bacterial growth and cell surface hydrophobicity of lactobacilli. J Food Sci 79(12):M2485–M2490. https://doi.org/10.1111/1750-3841.12695

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Liu W, Crott JW, Lyu L, Pfalzer AC, Li J, Choi SW, Yang Y, Mason JB, Liu Z (2016) Diet- and genetically-induced obesity produces alterations in the microbiome, inflammation and wnt pathway in the intestine of Apc(+/1638N) mice: comparisons and contrasts. J Cancer 7(13):1780–1790. https://doi.org/10.7150/jca.15792

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Fan P, Liu P, Song P, Chen X, Ma X (2017) Moderate dietary protein restriction alters the composition of gut microbiota and improves ileal barrier function in adult pig model. Sci Rep 7:43412. https://doi.org/10.1038/srep43412

    Article  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Zhao X, Jiang Z, Yang F, Wang Y, Gao X, Wang Y, Chai X, Pan G, Zhu Y (2016) Sensitive and simplified detection of antibiotic influence on the dynamic and versatile changes of fecal short-chain fatty acids. PLoS One 11(12):e0167032. https://doi.org/10.1371/journal.pone.0167032

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Segata N, Izard J, Waldron L, Gevers D, Miropolsky L, Garrett WS, Huttenhower C (2011) Metagenomic biomarker discovery and explanation. Genome Biol 12(6):R60. https://doi.org/10.1186/gb-2011-12-6-r60

    Article  PubMed  PubMed Central  Google Scholar 

  26. 26.

    Atal S, Zamowski MJ, Cushman SW, Sampugna J (1994) Comparison of body weight and adipose tissue in male C57BI/6J mice fed diets with and without trans fatty acids. Lipids 29(5):319–325. https://doi.org/10.1007/BF02537184

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Dotan I, Werner L, Vigodman S, Weiss S, Brazowski E, Maharshak N, Chen O, Tulchinsky H, Halpern Z, Guzner-Gur H (2010) CXCL12 is a constitutive and inflammatory chemokine in the intestinal immune system. Inflamm Bowel Dis 16(4):583–592. https://doi.org/10.1002/ibd.21106

    Article  PubMed  Google Scholar 

  28. 28.

    Hernandez-Ruiz M, Zlotnik A (2017) Mucosal chemokines. J Interferon Cytokine Res 37(2):62–70. https://doi.org/10.1089/jir.2016.0076

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Mikami S, Nakase H, Yamamoto S, Takeda Y, Yoshino T, Kasahara K, Ueno S, Uza N, Oishi S, Fujii N, Nagasawa T, Chiba T (2008) Blockade of CXCL12/CXCR4 axis ameliorates murine experimental colitis. J Pharmacol Exp Ther 327(2):383–392. https://doi.org/10.1124/jpet.108.141085

    CAS  Article  PubMed  Google Scholar 

  30. 30.

    Turnbaugh PJ, Ridaura VK, Faith JJ, Rey FE, Knight R, Gordon JI (2009) The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice. Sci Transl Med 1(6):6ra14. https://doi.org/10.1126/scitranslmed.3000322

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Mozaffarian D, Katan MB, Ascherio A, Stampfer MJ, Willett WC (2006) Trans fatty acids and cardiovascular disease. N Engl J Med 354(15):1601–1613. https://doi.org/10.1056/NEJMra054035

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    Dinakaran V, Rathinavel A, Pushpanathan M, Sivakumar R, Gunasekaran P, Rajendhran J (2014) Elevated levels of circulating DNA in cardiovascular disease patients: metagenomic profiling of microbiome in the circulation. PLoS One 9(8):e105221. https://doi.org/10.1371/journal.pone.0105221

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Shin NR, Whon TW, Bae JW (2015) Proteobacteria: microbial signature of dysbiosis in gut microbiota. Trends Biotechnol 33(9):496–503. https://doi.org/10.1016/j.tibtech.2015.06.011

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  34. 34.

    Mujico JR, Baccan GC, Gheorghe A, Diaz LE, Marcos A (2013) Changes in gut microbiota due to supplemented fatty acids in diet-induced obese mice. Br J Nutr 110(4):711–720. https://doi.org/10.1017/S0007114512005612

    CAS  Article  PubMed  Google Scholar 

  35. 35.

    Hwang I, Park YJ, Kim YR, Kim YN, Ka S, Lee HY, Seong JK, Seok YJ, Kim JB (2015) Alteration of gut microbiota by vancomycin and bacitracin improves insulin resistance via glucagon-like peptide 1 in diet-induced obesity. FASEB J 29(6):2397–2411. https://doi.org/10.1096/fj.14-265983

    CAS  Article  PubMed  Google Scholar 

  36. 36.

    Yamashita T, Emoto T, Sasaki N, Hirata KI (2016) Gut microbiota and coronary artery disease. Int Heart J 57(6):663–671. https://doi.org/10.1536/ihj.16-414

    CAS  Article  PubMed  Google Scholar 

  37. 37.

    Tomasova L, Konopelski P, Ufnal M (2016) Gut bacteria and hydrogen sulfide: the new old players in circulatory system homeostasis. Molecules 21(11). https://doi.org/10.3390/molecules21111558

  38. 38.

    Figliuolo VR, Dos Santos LM, Abalo A, Nanini H, Santos A, Brittes NM, Bernardazzi C, de Souza HSP, Vieira LQ, Coutinho-Silva R, Coutinho C (2017) Sulfate-reducing bacteria stimulate gut immune responses and contribute to inflammation in experimental colitis. Life Sci 189:29–38. https://doi.org/10.1016/j.lfs.2017.09.014

    CAS  Article  PubMed  Google Scholar 

  39. 39.

    Ijssennagger N, van der Meer R, van Mil SWC (2016) Sulfide as a mucus barrier-breaker in inflammatory bowel disease? Trends Mol Med 22(3):190–199. https://doi.org/10.1016/j.molmed.2016.01.002

    CAS  Article  PubMed  Google Scholar 

  40. 40.

    Endo Y, Kamisada S, Fujimoto K, Saito T (2006) Trans fatty acids promote the growth of some Lactobacillus strains. J Gen Appl Microbiol 52(1):29–35

    CAS  Article  Google Scholar 

  41. 41.

    Zeng H, Liu J, Jackson MI, Zhao FQ, Yan L, Combs GF Jr (2013) Fatty liver accompanies an increase in Lactobacillus species in the hind gut of C57BL/6 mice fed a high-fat diet. J Nutr 143(5):627–631. https://doi.org/10.3945/jn.112.172460

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  42. 42.

    Consolandi C, Turroni S, Emmi G, Severgnini M, Fiori J, Peano C, Biagi E, Grassi A, Rampelli S, Silvestri E, Centanni M, Cianchi F, Gotti R, Emmi L, Brigidi P, Bizzaro N, De Bellis G, Prisco D, Candela M, D’Elios MM (2015) Behcet’s syndrome patients exhibit specific microbiome signature. Autoimmun Rev 14(4):269–276. https://doi.org/10.1016/j.autrev.2014.11.009

    Article  PubMed  Google Scholar 

  43. 43.

    Reeves AE, Koenigsknecht MJ, Bergin IL, Young VB (2012) Suppression of Clostridium difficile in the gastrointestinal tracts of germfree mice inoculated with a murine isolate from the family Lachnospiraceae. Infect Immun 80(11):3786–3794. https://doi.org/10.1128/IAI.00647-12

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  44. 44.

    Wang T, Cai G, Qiu Y, Fei N, Zhang M, Pang X, Jia W, Cai S, Zhao L (2012) Structural segregation of gut microbiota between colorectal cancer patients and healthy volunteers. ISME J 6(2):320–329. https://doi.org/10.1038/ismej.2011.109

    CAS  Article  PubMed  Google Scholar 

  45. 45.

    Marques TM, Wall R, O’Sullivan O, Fitzgerald GF, Shanahan F, Quigley EM, Cotter PD, Cryan JF, Dinan TG, Ross RP, Stanton C (2015) Dietary trans-10, cis-12-conjugated linoleic acid alters fatty acid metabolism and microbiota composition in mice. Br J Nutr 113(5):728–738. https://doi.org/10.1017/S0007114514004206

    CAS  Article  PubMed  Google Scholar 

  46. 46.

    Del Chierico F, Nobili V, Vernocchi P, Russo A, Stefanis C, Gnani D, Furlanello C, Zandona A, Paci P, Capuani G, Dallapiccola B, Miccheli A, Alisi A, Putignani L (2017) Gut microbiota profiling of pediatric nonalcoholic fatty liver disease and obese patients unveiled by an integrated meta-omics-based approach. Hepatology 65(2):451–464. https://doi.org/10.1002/hep.28572

    CAS  Article  PubMed  Google Scholar 

  47. 47.

    Obara N, Fukushima K, Ueno Y, Wakui Y, Kimura O, Tamai K, Kakazu E, Inoue J, Kondo Y, Ogawa N, Sato K, Tsuduki T, Ishida K, Shimosegawa T (2010) Possible involvement and the mechanisms of excess trans-fatty acid consumption in severe NAFLD in mice. J Hepatol 53(2):326–334. https://doi.org/10.1016/j.jhep.2010.02.029

    CAS  Article  PubMed  Google Scholar 

  48. 48.

    Neuschwander-Tetri BA, Ford DA, Acharya S, Gilkey G, Basaranoglu M, Tetri LH, Brunt EM (2012) Dietary trans-fatty acid induced NASH is normalized following loss of trans-fatty acids from hepatic lipid pools. Lipids 47(10):941–950. https://doi.org/10.1007/s11745-012-3709-7

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  49. 49.

    Henkel J, Coleman CD, Schraplau A, Jhrens K, Weber D, Castro JP, Hugo M, Schulz TJ, Kramer S, Schurmann A, Puschel GP (2017) Induction of steatohepatitis (NASH) with insulin resistance in wildtype B6 mice by a western-type diet containing soybean oil and cholesterol. Mol Med. https://doi.org/10.2119/molmed.2016.00203

    Article  PubMed  PubMed Central  Google Scholar 

  50. 50.

    Jeyapal S, Putcha UK, Mullapudi VS, Ghosh S, Sakamuri A, Kona SR, Vadakattu SS, Madakasira C, Ibrahim A (2017) Chronic consumption of fructose in combination with trans fatty acids but not with saturated fatty acids induces nonalcoholic steatohepatitis with fibrosis in rats. Eur J Nutr. https://doi.org/10.1007/s00394-017-1492-1

    Article  PubMed  Google Scholar 

  51. 51.

    Sun J, Kato I (2016) Gut microbiota, inflammation and colorectal cancer. Genes Dis 3(2):130–143. https://doi.org/10.1016/j.gendis.2016.03.004

    Article  PubMed  PubMed Central  Google Scholar 

  52. 52.

    Kavanagh K, Jones KL, Sawyer J, Kelley K, Carr JJ, Wagner JD, Rudel LL (2007) Trans fat diet induces abdominal obesity and changes in insulin sensitivity in monkeys. Obesity (Silver Spring) 15(7):1675–1684. https://doi.org/10.1038/oby.2007.200

    CAS  Article  Google Scholar 

  53. 53.

    Chajes V, Biessy C, Ferrari P, Romieu I, Freisling H, Huybrechts I, Scalbert A, Bueno de Mesquita B, Romaguera D, Gunter MJ, Vineis P, Hansen CP, Jakobsen MU, Clavel-Chapelon F, Fagherazzi G, Boutron-Ruault MC, Katzke V, Neamat-Allah J, Boeing H, Bachlechner U, Trichopoulou A, Naska A, Orfanos P, Pala V, Masala G, Mattiello A, Skeie G, Weiderpass E, Agudo A, Huerta JM, Ardanaz E, Sanchez MJ, Dorronsoro M, Quiros JR, Johansson I, Winkvist A, Sonested E, Key T, Khaw KT, Wareham NJ, Peeters PH, Slimani N (2015) Plasma elaidic acid level as biomarker of industrial trans fatty acids and risk of weight change: report from the EPIC study. PLoS One 10(2):e0118206. https://doi.org/10.1371/journal.pone.0118206

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  54. 54.

    Machado RM, Stefano JT, Oliveira CP, Mello ES, Ferreira FD, Nunes VS, de Lima VM, Quintao EC, Catanozi S, Nakandakare ER, Lottenberg AM (2010) Intake of trans fatty acids causes nonalcoholic steatohepatitis and reduces adipose tissue fat content. J Nutr 140(6):1127–1132. https://doi.org/10.3945/jn.109.117937

    CAS  Article  PubMed  Google Scholar 

Download references

Funding

This project is supported by National Natural Science Foundation of China (31401487).

Author information

Affiliations

Authors

Corresponding authors

Correspondence to Wei Liu or Bin Qiu.

Ethics declarations

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 424 KB)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Ge, Y., Liu, W., Tao, H. et al. Effect of industrial trans-fatty acids-enriched diet on gut microbiota of C57BL/6 mice. Eur J Nutr 58, 2625–2638 (2019). https://doi.org/10.1007/s00394-018-1810-2

Download citation

Keywords

  • Trans-fatty acid
  • Gut microbiota
  • Short-chain fatty acid
  • 16S rRNA gene sequencing