Download PDF
Drug Res (Stuttg) 2016; 66(06): 300-305
DOI: 10.1055/s-0035-1569414
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Probiotic Yogurt Culture Bifidobacterium Animalis Subsp. Lactis BB-12 and Lactobacillus Acidophilus LA-5 Modulate the Cytokine Secretion by Peripheral Blood Mononuclear Cells from Patients with Ulcerative Colitis

A. Sheikhi
1   Department of Immunology, Faculty of Medicine, Dezful University of Medical Sciences, Dezful, Iran
2   Cellular and Molecular Immunology Research laboratory, Faculty of Medicine, Dezful University of Medical Sciences, Dezful, Iran
,
M. Shakerian
3   Sherkat Pegah Khoozestan, Dezful, Iran
,
H. Giti
4   Tehran Chemie Pharmaceutical Company, Tehran, Iran
,
M. Baghaeifar
3   Sherkat Pegah Khoozestan, Dezful, Iran
,
A. Jafarzadeh
5   Department of Immunology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
,
V. Ghaed
1   Department of Immunology, Faculty of Medicine, Dezful University of Medical Sciences, Dezful, Iran
,
M. R. Heibor
1   Department of Immunology, Faculty of Medicine, Dezful University of Medical Sciences, Dezful, Iran
,
N. Baharifar
6   Department of Microbiology, Azad University, Boroujerd, Iran
,
Z. Dadafarin
7   Department of Microbiology, Azad University, Arak, Iran
,
G. Bashirpour
8   Department of Internal Medicine, School of Medicine, Dezful University of Medical Sciences, Dezful, Iran
› Author Affiliations
Further Information

Publication History

received 26 November 2015

accepted 17 January 2016

Publication Date:
24 February 2016 (online)

Also available at
   Permissions and Reprints

Abstract

Background: There are some evidences for the immunomodulation disorders in the response to intestinal microbiota in inflammatory bowel disease. Yogurt is a fermented milk product made with a starter culture consisting of different probiotics which could be colonized in intestine. However, the role of probiotics in the aetiopathogenesis of ulcerative colitis (UC) has not been clarified. To determine how the immune system responds to these bacteria this study was planned.

Methods: Bifidobacterium lactis BB-12 (B. lactis) and Lactobacillus acidophilus LA-5 (L. acidophilus) were cultivated on MRS broth. PBMCs of 36 UC patients were separated by Ficoll-Hypaque centrifugation and co-cultured with different concentrations of UV killed bacteria in RPMI-1 640 plus 10% FCS for 48/72 h. IL-10, TGF-β, IFN-γ and TNF-α were measured in supernatant of PBMCs by ELISA.

Results: Both bacteria significantly augmented IL-10, TGF-β, IFN-γ and TNF-α compared to control (p<0.001). The secretion levels of IL-10 and TGF-β by B. lactis- compared to L. acidophilus-stimulated PBMCs were significantly higher (p<0.05, p<0.01 respectively). The secretion levels of TNF-α and IFN-γ by PBMCs after 72 h were significantly lower compared to 48 h stimulation by B. lactis (p<0.001, p<0.035 respectively).

Conclusion: These data show that both probiotics may trigger the pro- and anti-inflammatory immune response of UC patients. It seems that IL-10/TGF-β uprising by B. lactis could be the reason of TNF-α/IFN-γ reduction. Therefore albeit B. lactis still stimulates the effector Th cells but because of more stimulatory effect on Tregs, it could be a good potential therapeutic candidate for further investigation.

Key words

immunomodulation - ulcerative colitis - bifidobacterium lactis - lactobacillus acidophilus - probiotics
 

  • References

  • 1 Molodecky NA, Soon IS, Rabi DM et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology 2012; 142: 46-54 e42
    CrossrefPubMedGoogle Scholar
  • 2 Podolsky DK. Inflammatory bowel disease. N Engl J Med 2002; 347: 417-429
    CrossrefPubMedGoogle Scholar
  • 3 Zoetendal EG, Rajilic-Stojanovic M, de Vos WM. High-throughput diversity and functionality analysis of the gastrointestinal tract microbiota. Gut 2008; 57: 1605-1615
    CrossrefPubMedGoogle Scholar
  • 4 Meydani SN, Ha WK. Immunologic effects of yogurt. Am J Clin Nutr 2000; 71: 861-872 Review
    PubMedGoogle Scholar
  • 5 Sartor RB. Therapeutic manipulation of the enteric microflora in inflammatory bowel diseases: antibiotics, probiotics, and prebiotics. Gastroenterology 2004; 126: 1620-1633
    CrossrefPubMedGoogle Scholar
  • 6 Campieri M, Gionchetti P. Probiotics in inflammatory bowel disease: new insight to pathogenesis or a possible therapeutic alternative?. Gastroenterology 1999; 116: 1246-1249
    CrossrefPubMedGoogle Scholar
  • 7 Niers LE, Timmerman HM, Rijkers GT et al. Identification of strong interleukin-10 inducing lactic acid bacteria which downregulate T helper type 2 cytokines. Clin Exp Allergy 2005; 35: 1481-1489
    CrossrefPubMedGoogle Scholar
  • 8 Hirahara K, Poholek A, Vahedi G et al. Mechanisms underlying helper T-cell plasticity: implications for immune-mediated disease. J Allergy Clin Immunol 2013; 131: 1276-1287
    CrossrefPubMedGoogle Scholar
  • 9 Yamane H, Paul WE. Early signaling events that underlie fate decisions of naive CD4(+) T cells toward distinct T-helper cell subsets. Immunol Rev 2013; 252: 12-23
    CrossrefPubMedGoogle Scholar
  • 10 Lavasani S, Dzhambazov B, Nouri M et al. A novel probiotic mixture exerts a therapeutic effect on experimental autoimmune encephalomyelitis mediated by IL-10 producing regulatory T cells. PLoS ONE 2010; 5: 1-11
    PubMedGoogle Scholar
  • 11 Dahlén R, Magnusson MK, Bajor A et al. Global mucosal and serum cytokine profile in patients with ulcerative colitis undergoing anti-TNF therapy. Scand J Gastroenterol. 2015; 16: 1-9
    PubMedGoogle Scholar
  • 12 Ghouri YA, Richards DM, Rahimi EF et al. Systematic review of randomized controlled trials of probiotics, prebiotics, and synbiotics in inflammatory bowel disease. Clin Exp Gastroenterol 2014; 9: 473-487 Review
    PubMedGoogle Scholar
  • 13 Berg D, Clemente JC, Colombel JF. Can inflammatory bowel disease be permanently treated with short-term interventions on the microbiome?. Expert Rev Gastroenterol Hepatol 2015; 10: 1-15
    PubMedGoogle Scholar
  • 14 Sheikhi A, Saadati K, Jafarzadeh A et al. Augmenting the expression of NKp44 molecule and the natural killer activity in peripheral blood mononuclear cells from patients with malignant colorectal carcinoma. Drug Res (Stuttg) 2014; 64: 281-286
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Sheikhi A, Saadati K, Salmani R et al. In vitro modulation of natural killer activity of human peripheral blood mononuclear cells against prostate tumor cell line. Immunopharmacol Immunotoxicol 2011; 33: 700-708
    CrossrefPubMedGoogle Scholar
  • 16 Sheikhi A, Nazarian M, Khadem-Al-Melleh A et al. In-vitro effects of Mycobacterium bovis BCG-lysate and its derived heat shock proteins on cytokines secretion by blood mononuclear cells of rheumatoid arthritis patients in comparison with healthy controls. Int Immunopharmacol 2008; 8: 887-892
    CrossrefPubMedGoogle Scholar
  • 17 Amirghofran Z, Sheikhi AK, Kumar PV et al. Soluble HLA class I molecules in malignant pleural and peritoneal effusions and its possible role on NK and LAK cytotoxicity. J Cancer Res Clin Oncol 2002; 128: 443-448
    CrossrefPubMedGoogle Scholar
  • 18 Fuss IJ, Neurath M, Boirivant M et al. Disparate CD4+lamina propria (LP) lymphokine secretion profiles in inflammatory bowel disease. Crohn’s disease LP cells manifest increased secretion of IFNgamma, whereas ulcerative colitis LP cells manifest increased secretion of IL-5. J Immunol 1996; 157: 1261-1270
    PubMedGoogle Scholar
  • 19 Heller F, Florian P, Bojarski C et al. Interleukin-13 is the key effector Th2 cytokine in ulcerative colitis that affects epithelial tight junctions, apoptosis, and cell restitution. Gastroenterology 2005; 129: 550-564
    CrossrefPubMedGoogle Scholar
  • 20 Strober W, Fuss I, Mannon P. The fundamental basis of inflammatory bowel disease. J Clin Invest 2007; 117: 514-521
    CrossrefPubMedGoogle Scholar
  • 21 Abraham C, Medzhitov R. Interactions between the host innate immune system and microbes in inflammatory bowel disease. Gastroenterology 2011; 140: 1729-1737
    CrossrefPubMedGoogle Scholar
  • 22 Danese S. Immune and nonimmune components orchestrate the pathogenesis of inflammatory bowel disease. Am J Physiol Gastrointest Liver Physiol 2011; 300: G716-G722
    CrossrefPubMedGoogle Scholar
  • 23 Hanauer SB. Medical therapy for ulcerative colitis. Gastroenterology 2004; 126: 1582-1592
    CrossrefPubMedGoogle Scholar
  • 24 Zheng B, van Bergenhenegouwen J, Overbeek S et al Bifidobacterium breve attenuates murine dextran sodium sulfate-induced colitis and increases regulatory T cell responses. PLoS One 2014; 9: e95441
    CrossrefPubMedGoogle Scholar
  • 25 Imaoka A, Shima T, Kato K et al. Anti-inflammatory activity of probiotic Bifidobacterium: Enhancement of IL-10 production in peripheral blood mononuclear cells from ulcerative colitis patients and inhibition of IL-8 secretion in HT-29 cells. World J Gastroenterol 2008; 14: 2511-2516
    CrossrefPubMedGoogle Scholar
  • 26 Kato K, Mizuno S, Umesaki Y et al. Randomized placebo-controlled trial assessing the effect of bifidobacteria-fermented milk on active ulcerative colitis. Aliment Pharmacol Ther 2004; 20: 1133-1141
    CrossrefPubMedGoogle Scholar
  • 27 Peran L, Camuesco D, Comalada M et al. A comparative study of the preventative effects exerted by three probiotics, Bifidobacterium lactis, Lactobacillus casei and Lactobacillus acidophilus, in the TNBS model of rat colitis. J Appl Microbiol 2007; 103: 836-844
    CrossrefPubMedGoogle Scholar
  • 28 Ohman L, Dahlen R, Isaksson S et al. Serum IL-17A in newly diagnosed treatment-naive patients with ulcerative colitis reflects clinical disease severity and predicts the course of disease. Inflamm Bowel Dis 2013; 19: 2433-2439
    CrossrefPubMedGoogle Scholar
  • 29 Rismo R, Olsen T, Cui G et al. Mucosal cytokine gene expression profiles as biomarkers of response to infliximab in ulcerative colitis. Scand J Gastroenterol 2012; 47: 538-547
    CrossrefPubMedGoogle Scholar
  • 30 Olsen T, Goll R, Cui G et al. Tissue levels of tumor necrosis factor-alpha correlates with grade of inflammation in untreated ulcerative colitis. Scand J Gastroenterol 2007; 42: 1312-1320
    CrossrefPubMedGoogle Scholar
  • 31 Rodriguez-Peralvarez ML, Garcia-Sanchez V, Villar- Pastor CM et al. Role of serum cytokine profile in ulcerative colitis assessment. Inflamm Bowel Dis 2012; 18: 1864-1871
    CrossrefPubMedGoogle Scholar
  • 32 Holmen N, Lundgren A, Lundin S et al. Functional CD4+CD25 high regulatory T cells are enriched in the colonic mucosa of patients with active ulcerative colitis and increase with disease activity. Inflamm Bowel Dis 2006; 12: 447-456
    CrossrefPubMedGoogle Scholar
  • 33 Olsen T, Cui G, Goll R et al. Infliximab therapy decreases the levels of TNF-alpha and IFN-gamma mRNA in colonic mucosa of ulcerative colitis. Scand J Gastroenterol 2009; 44: 727-735
    CrossrefPubMedGoogle Scholar
  • 34 Hassan C, Ierardi E, Burattini O et al. Tumour necrosis factor alpha downregulation parallels inflammatory regression in ulcerative colitis patients treated with infliximab. Dig Liver Dis 2007; 39: 811-817
    CrossrefPubMedGoogle Scholar
  • 35 Masuda H, Iwai S, Tanaka T et al. Expression of IL-8, TNF-alpha and IFN-gamma m-RNA in ulcerative colitis, particularly in patients with inactive phase. J Clin Lab Immunol 1995; 46: 111-123
    PubMedGoogle Scholar
  • 36 Singh B, Read S, Asseman C et al. Control of intestinal inflammation by regulatory T cells. Immunol Rev 2001; 182: 190-200
    CrossrefPubMedGoogle Scholar
  • 37 Mottet C, Uhlig HH, Powrie F. Cutting edge: cure of colitis by CD4+CD25+ regulatory T cells. J Immunol 2003; 170: 3939-3943
    CrossrefPubMedGoogle Scholar
  • 38 Uhlig HH, Coombes J, Mottet C et al. Characterization of Foxp3+CD4+CD25+ and IL-10-secreting CD4+CD25+ T cells during cure of colitis. J Immunol 2006; 177: 5852-5860
    CrossrefPubMedGoogle Scholar
  • 39 Bacchetta R, Passerini L, Gambineri E et al. Defective regulatory and effector T cell functions in patients with FOXP3 mutations. J Clin Invest 2006; 116: 1713-1722
    CrossrefPubMedGoogle Scholar
  • 40 McMurchy AN, Di Nunzio S, Roncarolo MG et al. Molecular regulation of cellular immunity by FOXP3. Adv Exp Med Biol 2009; 665: 30-46
    PubMedGoogle Scholar
  • 41 Himmel ME, Yao Y, Orban PC et al. Regulatory T-cell therapy for inflammatory bowel disease: more questions than answers. Immunology 2012; 136: 115-122
    CrossrefPubMedGoogle Scholar
  • 42 Pronio A, Montesani C, Butteroni C et al. Probiotic administration in patients with ileal pouch-anal anastomosis for ulcerative colitis is associated with expansion of mucosal regulatory cells. Inflamm Bowel Dis 2008; 14: 662-668
    CrossrefPubMedGoogle Scholar
  • 43 Al-Hassi HO, Mann ER, Sanchez B et al. Altered human gut dendritic cell properties in ulcerative colitis are reversed by Lactobacillus plantarum extracellular encrypted peptide STp. Mol Nutr Food Res 2014; 58: 1132-1143
    CrossrefPubMedGoogle Scholar