Effect of short-chain fatty acids on the expression of genes involved in short-chain fatty acid transporters and inflammatory response in goat jejunum epithelial cells

  • Kang Zhan
  • MaoCheng Jiang
  • Xiaoxiao Gong
  • GuoQi Zhao


Short-chain fatty acids (SCFAs) produced by microbial fermentation of dietary fibers are utilized by intestinal epithelial cells to provide an energy source for the ruminant. Although the regulation of mRNA expression and inflammatory response involved in SCFAs is established in other animals and tissues, the underlying mechanisms of the inflammatory response by SCFAs in goat jejunum epithelial cells (GJECs) have not been understood. Therefore, the objective of the study is to investigate the underlying mechanisms of the effects of SCFAs on SCFA transporters and inflammatory response in GJECs. These results showed that the acetate, butyrate, and SCFA concentration were markedly reduced in GJECs (p < 0.01). In addition, the propionate concentration was significantly decreased in GJECs (p < 0.05). The mRNA abundance of monocarboxylate transporter 1 (MCT1), MCT4, NHE1, and putative anion transporter 1 (PAT1) was elevated (p < 0.05) by 20 mM SCFAs at pH 7.4 compared with exposure to the pH group. The anion exchanger 2 (AE2) was increased (p < 0.05) by 20 mM SCFAs at pH 6.2. The mRNA abundance of vH+ ATPase B subunit (vH+ ATPase) was attenuated by SCFAs. For inflammatory responses, IL-1β and TNF-α were increased with SCFAs (p < 0.05). In addition, IκBα involved in NF-κB signaling pathways was disrupted by SCFAs. Consistently, p-p65 signaling molecule was enhanced by adding SCFAs. However, IL-6 was attenuated by adding SCFAs (p < 0.05). Furthermore, p-ErK1/2 mitogen-activated protein kinase (MAPK) signaling pathway was downregulated by adding SCFAs. In conclusion, these novel findings demonstrated that mRNA abundance involved in SCFA absorption is probably associated to SCFAs and pH value, and mechanism of the inflammatory response by SCFAs may be involved in NF-κB and p-ErK1/2 MAPK signaling pathways in GJECs. These pathways may mediate protective inflammation response in GJECs.


SCFAs Goat intestinal epithelial cells Inflammatory response 


Funding information

This study was supported by the China Agriculture Research System (CARS-36) and the National Natural Science Foundation of China (No. 31572430).

Compliance with ethical standards

Animal slaughter followed the Ethics Committee of the Institute of Yangzhou University.


  1. Albrecht E, Kolisek M, Viergutz T, Zitnan R, Schweigel M (2008) Molecular identification, immunolocalization, and functional activity of a vacuolar-type H(+)-ATPase in bovine rumen epithelium. J Comp Physiol B 178(3):285–295Google Scholar
  2. Aschenbach JR, Penner GB, Stumpff F, Gäbel G (2011) Ruminant nutrition symposium: role of fermentation acid absorption in the regulation of ruminal pH. J Anim Sci 89(4):1092–1107. CrossRefPubMedGoogle Scholar
  3. Böcker U, Nebe T, Herweck F, Holt L, Panja A, Jobin C, Rossol S, Sartor R B, Singer MV (2003) Butyrate modulates intestinal epithelial cell-mediated neutrophil migration. Clin Exp Immunol 131(1):53–60. CrossRefPubMedPubMedCentralGoogle Scholar
  4. Bondzio A, Gabler C, Badewien-Rentzsch B, Schulze P, Martens H, Einspanier R (2011) Identification of differentially expressed proteins in ruminal epithelium in response to a concentrate supplemented diet. Am J Physiol Gastrointest Liver Physiol 301(2):G260–G268. CrossRefPubMedGoogle Scholar
  5. Erwin ES, Marco GJ, Emery EM (1961) Volatile fatty acid analyses of blood and rumen fluid by gas chromatography. J Dairy Sci 44(9):1768–1771Google Scholar
  6. Etschmann B, Heipertz KS, von der Schulenburg A, Schweigel M (2006) A vH+-ATPase is present in cultured sheep ruminal epithelial cells. Am J Physiol Gastrointest Liver Physiol 291(6):G1171–9Google Scholar
  7. Dagmar K, Thomas S (2006) NF-κB and cytokines. Vitam Horm 74:283–300CrossRefGoogle Scholar
  8. George SP, Wang Y, Mathew S, Srinivasan K, Khurana S (2007) Dimerization and actin-bundling properties of villin and its role in the assembly of epithelial cell brush borders. J Biol Chem 282(36):26528–26265. CrossRefPubMedGoogle Scholar
  9. Hadjiagapiou C, Schmidt L, Dudeja PK, Layden TJ, Ramaswamy K (2000) Mechanism(s) of butyrate transport in Caco-2 cells: role of monocarboxylate transporter 1. Am J Physiol Gastrointest Liver Physiol 279(4):G775–G780. CrossRefPubMedGoogle Scholar
  10. Hamer HM, De Preter V, Windey K, Verbeke K (2012) Functional analysis of colonic bacterial metabolism: relevant to health? Am J Physiol Gastrointest Liver Physiol 302:1–9CrossRefGoogle Scholar
  11. Hass R, Busche R, Luciano L, Reale E, Engelhardt WV (1997) Lack of butyrate is associated with induction of BAX and subsequent apoptosis in the proximal colon of guinea pig. Gastroenterology 112(3):875–881. CrossRefPubMedGoogle Scholar
  12. Ihara T, Tsujikawa T, Fujiyama Y, Bamba T (2000) Regulation of PepT1 transporter expression in the rat small intestine under malnourished condition. Digestion 61(1):59–67. CrossRefPubMedGoogle Scholar
  13. Inan MS, Rasoulpour RJ, Yin L, Hubbard AK, Rosenberg DW, Giardina C (2000) The luminal short-chain fatty acid butyrate modulates NF-B activity in a human colonic epithelial cell line. Gastroenterology 118(4):724–734. CrossRefPubMedGoogle Scholar
  14. Kim MH, Kang SG, Park JH, Yanagisawa M, Kim CH (2013) Short-chain fatty acids activate GPR41 and GPR43 on intestinal epithelial cells to promote inflammatory responses in mice. Gastroenterology 145(2):396–406. CrossRefPubMedGoogle Scholar
  15. Kles KA, Chang EB (2006) Short-chain fatty acids impact on intestinal adaptation, inflammation, carcinoma, and failure. Gastroenterology 130(2):S100–S105. CrossRefPubMedGoogle Scholar
  16. Le PE, Loison C, Struyf S, Springael JY, Lannoy V, Decobecq ME, Brezillon S, Dupriez V, Vassart G, Van Damme J, Parmentier M, Detheux M (2003) Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation. J Biol Chem 278(28):25481–25489. CrossRefGoogle Scholar
  17. Leonhard-Marek S, Stumpff F, Martens H (2010) Transport of cations and anions across forestomach epithelia: conclusions from in vitro studies. Animal 4(07):1037–1056. CrossRefPubMedGoogle Scholar
  18. Lu Z, Yao L, Jiang Z, Aschenbach JR, Martens H, Shen Z (2016) Acidic pH and short-chain fatty acids activate Na+ transport but differentially modulate expression of Na+/H+ exchanger isoforms 1, 2, and 3 in omasal epithelium. J Dairy Sci 99(1):733–745. CrossRefPubMedGoogle Scholar
  19. Macia L, Thorburn AN, Binge LC, Marino E, Rogers KE, Maslowski KM, Vieira AT, Kranich J, Mackay CR (2012) Microbial influences on epithelial integrity and immune function as a basis for inflammatory diseases. Immunol Rev 245(1):164–176. CrossRefPubMedGoogle Scholar
  20. Maslowski KM, Mackay CR (2011) Diet, gut microbiota and immune responses. Nat Immunol 12(1):5–9. CrossRefPubMedGoogle Scholar
  21. Maslowski KM, Vieira AT, Ng A, Kranich J, Sierro F, Yu D, Schilter HC, Rolph MS, Mackay F, Artis D, Xavier RJ, Teixeira MM, Mackay CR (2009) Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 461(7268):1282–1286. CrossRefPubMedPubMedCentralGoogle Scholar
  22. Metzler-Zebeli BU, Hollmann M, Sabitzer S, Podstatzky-Lichtenstein L, Klein D, Zebeli Q (2013) Epithelial response to high-grain diets involves alteration in nutrient transporters and Na+/K+-ATPase mRNA expression in rumen and colon of goats. J Anim Sci 91(9):4256–4266. CrossRefPubMedGoogle Scholar
  23. Miyazawa K, Hondo T, Kanaya T, Tanaka S, Takakura I, Itani W, Rose MT, Kitazawa H, Yamaguchi T, Aso H (2010) Characterization of newly established bovine intestinal epithelial cell line. Histochem Cell Biol 133(1):125–134. CrossRefPubMedGoogle Scholar
  24. Oh DY, Talukdar S, Bae EJ, Imamura T, Morinaga H, Fan W, Li P, Lu WJ, Watkins SM, Olefsky JM (2010) Gpr120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell 142(5):687–698. CrossRefPubMedPubMedCentralGoogle Scholar
  25. Scheidereit C (2006) IkappaB kinase complexes: gateways to NF-kappaB activation and transcription. Oncogene 25(51):6685–6705. CrossRefPubMedGoogle Scholar
  26. Scheppach W (1996) Treatment of distal ulcerative colitis with short-chain fatty acid enemas. A placebo-controlled trial. German-Austrian SCFA Study Group. Dig Dis Sci 41(11):2254–2259. CrossRefPubMedGoogle Scholar
  27. Steele MA, Vandervoort G, AlZahal O, Hook SE, Matthews JC, McBride BW (2011) Rumen epithelial adaptation to high-grain diets involves the coordinated regulation of genes involved in cholesterol homeostasis. Physiol Genomics 43(6):308–316. CrossRefPubMedGoogle Scholar
  28. Somers J, Smith C, Donnison M, Wells DN, Henderson H, McLeay L, Pfeffer PL (2006) Gene expression profiling of individual bovine nuclear transfer blastocysts. Reproduction 131(6):1073–1084Google Scholar
  29. Tedelind S, Westberg F, Kjerrulf M, Vidal A (2007) Anti-inflammatory properties of the short-chain fatty acids acetate and propionate: a study with relevance to inflammatory bowel disease. World J Gastroenterol 13(20):2826–2832. CrossRefPubMedPubMedCentralGoogle Scholar
  30. Thwaites DT, Anderson CM (2007) H+-coupled nutrient, micronutrient and drug transporters in the mammalian small intestine. Exp Physiol 92(4):603–619. CrossRefPubMedPubMedCentralGoogle Scholar
  31. Wu J, Zhou Z, Hu Y, Dong S (2012) Butyrate-induced GPR41 activation inhibits histone acetylation and cell growth. J Genet Genomics 39(8):375–384. CrossRefPubMedGoogle Scholar
  32. Yan L, Zhang B, Shen Z (2014) Dietary modulation of the expression of genes involved in short-chain fatty acid absorption in the rumen epithelium is related to short-chain fatty acid concentration and pH in the rumen of goats. J Dairy Sci 97(9):5668–5675. CrossRefPubMedGoogle Scholar
  33. Yang W, Shen Z, Martens H (2012) An energy-rich diet enhances expression of Na+/H+ exchanger isoform 1 and 3 messenger RNA in rumen epithelium of goat. J Anim Sci 90(1):307–317. CrossRefPubMedGoogle Scholar

Copyright information

© The Society for In Vitro Biology 2018

Authors and Affiliations

  • Kang Zhan
    • 1
  • MaoCheng Jiang
    • 1
  • Xiaoxiao Gong
    • 1
  • GuoQi Zhao
    • 1
  1. 1.Institute of Animal Culture Collection and Application, College of Animal Science and TechnologyYangzhou UniversityYangzhouChina

Personalised recommendations