Abstract
Background
Intestinal homeostasis plays an important role in bacteria-derived complications in cirrhosis. Intestinal lymphocytes are responsible for immune effector functions and can be modulated by certain probiotics. We evaluate the interaction between Bifidobacterium pseudocatenulatum CECT7765 and intestinal lymphocytes in mice with cirrhosis.
Animals and methods
Cirrhosis was induced by intragastrical administration of carbon tetrachloride in Balb/C mice. One week prior to laparotomy, animals received B. pseudocatenulatum CECT7765 (107, 109 or 1010 cfu/daily) or placebo. Chemokine receptor and cytokine expression were evaluated in intestinal lymphocytes. Gut permeability was studied by FITC-LPS recovery in vivo. Luminal antigens, inflammation and functional markers were evaluated in liver samples.
Results
Bifidobacterium pseudocatenulatum CECT7765 decreased the expression of pro-inflammatory chemokine receptors CCR6, CCR9, CXCR3 and CXCR6 in intestinal lymphocytes from cirrhotic mice in a concentration-dependent manner. The bifidobacterial strain induced a shift towards an anti-inflammatory cytokine profile in this cell subset. B. pseudocatenulatum CECT7765-induced inflammatory modulation was TLR2-mediated, as in vitro TLR2 blockade inhibited the reduction of TNF-alpha and its receptors and the increase of IL-10 and IL-10 receptor secretion. The recovery rate of administered fluorescence-labelled endotoxin was significantly and dose-dependently lowered with the bifidobacterial strain. The reduced intestinal permeability was associated with a decreased burden of bacterial antigens in the liver of mice treated with B. pseudocatenulatum CECT7765. Liver function and inflammation were improved with the use of the bifidobacterial strain at the highest dose tested (1010 cfu).
Conclusion
Bifidobacterium pseudocatenulatum CECT7765 improves gut homeostasis and prevents gut-derived complications in experimental chronic liver disease.
Similar content being viewed by others
References
Berg RD (1992) Bacterial translocation from the gastrointestinal tract. J Med 23:217–244
Wiest R, Garcia-Tsao G (2005) Bacterial translocation (BT) in cirrhosis. Hepatology 41:422–433
Yan AW, Fouts DE, Brandl J, Starkel P, Torralba M, Schott E et al (2011) Enteric dysbiosis associated with a mouse model of alcoholic liver disease. Hepatology 53:96–105
Gomez-Hurtado I, Santacruz A, Peiro G, Zapater P, Gutierrez A, Perez-Mateo M et al (2011) Gut microbiota dysbiosis is associated with inflammation and bacterial translocation in mice with CCl4-induced fibrosis. PLoSOne 6:e23037
Kirpich IA, McClain CJ (2012) Probiotics in the treatment of the liver diseases. J Am Coll Nutr 31:14–23
Stadlbauer V, Mookerjee RP, Hodges S, Wright GA, Davies NA, Jalan R (2008) Effect of probiotic treatment on deranged neutrophil function and cytokine responses in patients with compensated alcoholic cirrhosis. J Hepatol 48:945–951
Pereg D, Kotliroff A, Gadoth N, Hadary R, Lishner M, Kitay-Cohen Y (2011) Probiotics for patients with compensated liver cirrhosis: a double-blind placebo-controlled study. Nutrition 27:177–181
Moratalla A, Gomez-Hurtado I, Santacruz A, Moya A, Peiro G, Zapater P, et al. (2014) Protective effect of Bifidobacterium pseudocatenulatum CECT7765 against induced bacterial antigen translocation in experimental cirrhosis. Liver Int 34:850–858
Agace WW (2006) Tissue-tropic effector T cells: generation and targeting opportunities. Nat Rev Immunol 6:682–692
de Kivit S, Tobin MC, Forsyth CB, Keshavarzian A, Landay AL (2014) Regulation of intestinal immune responses through TLR activation: implications for pro- and prebiotics. Front Immunol 5:60
Jeon SG, Kayama H, Ueda Y, Takahashi T, Asahara T, Tsuji H et al (2012) Probiotic Bifidobacterium breve induces IL-10-producing Tr1 cells in the colon. PLoS Pathog 8:e1002714
Isono A, Katsuno T, Sato T, Nakagawa T, Kato Y, Sato N et al (2007) Clostridium butyricum TO-A culture supernatant downregulates TLR4 in human colonic epithelial cells. Dig Dis Sci 52:2963–2971
Hayashi A, Sato T, Kamada N, Mikami Y, Matsuoka K, Hisamatsu T et al (2013) A single strain of Clostridium butyricum induces intestinal IL-10-producing macrophages to suppress acute experimental colitis in mice. Cell Host Microbe 13:711–722
Mazmanian SK, Round JL, Kasper DL (2008) A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 453:620–625
Vizoso Pinto MG, Rodriguez Gomez M, Seifert S, Watzl B, Holzapfel WH, Franz CM (2009) Lactobacilli stimulate the innate immune response and modulate the TLR expression of HT29 intestinal epithelial cells in vitro. Int J Food Microbiol 133:86–93
Furrie E, Macfarlane S, Thomson G, Macfarlane GT, Microbiology and Gut Biology Group et al (2005) Toll-like receptors-2, -3 and -4 expression patterns on human colon and their regulation by mucosal-associated bacteria. Immunology 115:565–574
Kingma SD, Li N, Sun F, Valladares RB, Neu J, Lorca GL (2011) Lactobacillus johnsonii N6.2 stimulates the innate immune response through Toll-like receptor 9 in Caco-2 cells and increases intestinal crypt Paneth cell number in biobreeding diabetes-prone rats. J Nutr 141:1023–1028
Such J, Frances R, Munoz C, Zapater P, Casellas JA, Cifuentes A et al (2002) Detection and identification of bacterial DNA in patients with cirrhosis and culture-negative, nonneutrocytic ascites. Hepatology 36:135–141
Guarner C, Gonzalez-Navajas JM, Sanchez E, Soriano G, Frances R, Chiva M et al (2006) The detection of bacterial DNA in blood of rats with CCl(4)-induced cirrhosis with ascites represents episodes of bacterial translocation. Hepatology 44:633–639
Gautreaux MD, Gelder FB, Deitch EA, Berg RD (1995) Adoptive transfer of T lymphocytes to T-cell-depleted mice inhibits Escherichia coli translocation from the gastrointestinal tract. Infect Immun 63:3827–3834
Choudhry MA, Fazal N, Goto M, Gamelli RL, Sayeed MM (2002) Gut-associated lymphoid T cell suppression enhances bacterial translocation in alcohol and burn injury. Am J Physiol Gastrointest Liver Physiol 282:G937–G947
Stenstad H, Ericsson A, Johansson-Lindbom B, Svensson M, Marsal J, Mack M et al (2006) Gut-associated lymphoid tissue-primed CD4 + T cells display CCR9-dependent and -independent homing to the small intestine. Blood 107:3447–3454
Chu PS, Nakamoto N, Ebinuma H, Usui S, Saeki K, Matsumoto A et al (2013) C-C motif chemokine receptor 9 positive macrophages activate hepatic stellate cells and promote liver fibrosis in mice. Hepatology 58:337–350
Hammerich L, Bangen JM, Govaere O, Zimmermann HW, Gassler N, Huss S et al (2014) Chemokine receptor CCR6-dependent accumulation of gammadelta T cells in injured liver restricts hepatic inflammation and fibrosis. Hepatology 59:630–642
Helwig U, Lammers KM, Rizzello F, Brigidi P, Rohleder V, Caramelli E et al (2006) Lactobacilli, Bifidobacteria and E. coli nissle induce pro- and anti-inflammatory cytokines in peripheral blood mononuclear cells. World J Gastroenterol 12:5978–5986
Medina M, Izquierdo E, Ennahar S, Sanz Y (2007) Differential immunomodulatory properties of Bifidobacterium logum strains: relevance to probiotic selection and clinical applications. Clin Exp Immunol 150:531–538
Agrawal S, Agrawal A, Doughty B, Gerwitz A, Blenis J, Van Dyke T et al (2003) Cutting edge: different Toll-like receptor agonists instruct dendritic cells to induce distinct Th responses via differential modulation of extracellular signal-regulated kinase-mitogen-activated protein kinase and c-Fos. J Immunol 171:4984–4989
Dillon S, Agrawal A, Van Dyke T, Landreth G, McCauley L, Koh A et al (2004) A Toll-like receptor 2 ligand stimulates Th2 responses in vivo, via induction of extracellular signal-regulated kinase mitogen-activated protein kinase and c-Fos in dendritic cells. J Immunol 172:4733–4743
Redecke V, Hacker H, Datta SK, Fermin A, Pitha PM, Broide DH et al (2004) Cutting edge: activation of Toll-like receptor 2 induces a Th2 immune response and promotes experimental asthma. J Immunol 172:2739–2743
Plantinga TS, van Maren WW, van Bergenhenegouwen J, Hameetman M, Nierkens S, Jacobs C et al (2011) Differential Toll-like receptor recognition and induction of cytokine profile by Bifidobacterium breve and Lactobacillus strains of probiotics. Clin Vaccine Immunol 18:621–628
Hartmann P, Haimerl M, Mazagova M, Brenner DA, Schnabl B (2012) Toll-like receptor 2-mediated intestinal injury and enteric tumor necrosis factor receptor I contribute to liver fibrosis in mice. Gastroenterology 143(1330–1340):e1331
Frances R, Zapater P, Gonzalez-Navajas JM, Munoz C, Cano R, Moreu R et al (2008) Bacterial DNA in patients with cirrhosis and noninfected ascites mimics the soluble immune response established in patients with spontaneous bacterial peritonitis. Hepatology 47:978–985
Moorthy G, Murali MR, Devaraj SN (2009) Lactobacilli facilitate maintenance of intestinal membrane integrity during Shigella dysenteriae 1 infection in rats. Nutrition 25:350–358
Khailova L, Dvorak K, Arganbright KM, Halpern MD, Kinouchi T, Yajima M et al (2009) Bifidobacterium bifidum improves intestinal integrity in a rat model of necrotizing enterocolitis. Am J Physiol Gastrointest Liver Physiol 297:G940–G949
Mennigen R, Nolte K, Rijcken E, Utech M, Loeffler B, Senninger N et al (2009) Probiotic mixture VSL#3 protects the epithelial barrier by maintaining tight junction protein expression and preventing apoptosis in a murine model of colitis. Am J Physiol Gastrointest Liver Physiol 296:G1140–G1149
Zhou YK, Qin HL, Zhang M, Shen TY, Chen HQ, Ma YL et al (2012) Effects of Lactobacillus plantarum on gut barrier function in experimental obstructive jaundice. World J Gastroenterol 18:3977–3991
Sanchez E, Nieto JC, Boullosa A, Vidal S, Sancho FJ, Rossi G, et al. (2014) VSL#3 probiotic treatment decreases bacterial translocation in rats with carbon tetrachloride-induced cirrhosis. Liver Int 34:1504–1512
Velayudham A, Dolganiuc A, Ellis M, Petrasek J, Kodys K, Mandrekar P et al (2009) VSL#3 probiotic treatment attenuates fibrosis without changes in steatohepatitis in a diet-induced nonalcoholic steatohepatitis model in mice. Hepatology 49:989–997
Li Z, Yang S, Lin H, Huang J, Watkins PA, Moser AB et al (2003) Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease. Hepatology 37:343–350
Acknowledegments
This work has been supported by grants PI13/1443 from the Instituto de Salud Carlos III, Madrid, Spain, and AGL2011-25169 from MINECO, Spain; Moratalla A. is recipient of a grant ACIF-2012/015, Consellería d’Educació, Generalitat Valenciana, Spain. A. Moya is recipient of a FPU scholarship from MINECO, Spain.
Conflict of interest
On behalf of all authors, the corresponding author states that there is no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Moratalla, A., Gómez-Hurtado, I., Moya-Pérez, Á. et al. Bifidobacterium pseudocatenulatum CECT7765 promotes a TLR2-dependent anti-inflammatory response in intestinal lymphocytes from mice with cirrhosis. Eur J Nutr 55, 197–206 (2016). https://doi.org/10.1007/s00394-015-0837-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00394-015-0837-x