Faecalibacterium prausnitzii prevents physiological damages in a chronic low-grade inflammation murine model

BMC Microbiology

Luis G Bermúdez-Humarán³  Philippe Langella¹  Elena F Verdu¹  Premysl Bercik¹  Vassilia Theodorou²  Harry Sokol⁴  Jun Lu¹  Jennifer Jury¹  Jane M Natividad¹  Florian Chain³  Sylvie Miquel³  Rebeca Martín¹ 

[1] Farncombe Family Digestive Health Research Institute, McMaster University, 1200 Main St West, H.Sc. 3N6, Hamilton, Ontario, Canada;INRA, Neuro-Gastroenterology and Nutrition Team, UMR 1331 Toxalim, Toulouse, F-31931, France;AgroParisTech, UMR1319 Micalis, Jouy-en-Josas, F-78350, France;Department of Gastroenterology and Nutrition, AP-HP, Hôpital Saint-Antoine F-75012 and UPMC Univ Paris 06F-75005, Paris, France

关键词: Probiotics;    Low-grade inflammation;    IBD-remission;    Dysbiosis;    Microbiota;   

Others  :  1221684
DOI  :  10.1186/s12866-015-0400-1

 received in 2014-07-18, accepted in 2015-03-02,  发布年份 2015

【 摘 要 】

Background

The human gut houses one of the most complex and abundant ecosystems composed of up to 10¹³-10¹⁴ microorganisms. The importance of this intestinal microbiota is highlighted when a disruption of the intestinal ecosystem equilibrium appears (a phenomenon called dysbiosis) leading to an illness status, such as inflammatory bowel diseases (IBD). Indeed, the reduction of the commensal bacterium Faecalibacterium prausnitzii (one of the most prevalent intestinal bacterial species in healthy adults) has been correlated with several diseases, including IBD, and most importantly, it has been shown that this bacterium has anti-inflammatory and protective effects in pre-clinical models of colitis. Some dysbiosis disorders are characterized by functional and physiological alterations. Here, we report the beneficial effects of F. prausnitzii in the physiological changes induced by a chronic low-grade inflammation in a murine model. Chronic low-grade inflammation and gut dysfunction were induced in mice by two episodes of dinitro-benzene sulfonic acid (DNBS) instillations. Markers of inflammation, gut permeability, colonic serotonin and cytokine levels were studied. The effects of F. prausnitzii strain A2-165 and its culture supernatant (SN) were then investigated.

Results

No significant differences were observed in classical inflammation markers confirming that inflammation was subclinical. However, gut permeability, colonic serotonin levels and the colonic levels of the cytokines IL-6, INF-γ, IL-4 and IL-22 were higher in DNBS-treated than in untreated mice. Importantly, mice treated with either F. prausnitzii or its SN exhibited significant decreases in intestinal permeability, tissue cytokines and serotonin levels.

Conclusions

Our results show that F. prausnitzii and its SN had beneficial effects on intestinal epithelial barrier impairment in a chronic low-grade inflammation model. These observations confirm the potential of this bacterium as a novel probiotic treatment in the management of gut dysfunction and low-grade inflammation.

【 授权许可】

   
2015 Martín et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 6.

Figure 6.

【 参考文献 】

• [1]Martin R, Miquel S, Ulmer J, Langella P, Bermudez-Humaran LG. Gut ecosystem: how microbes help us. Benef Microbes. 2014; 5(3):219-33.
• [2]Tap J, Mondot S, Levenez F, Pelletier E, Caron C, Furet JP et al.. Towards the human intestinal microbiota phylogenetic core. Environ Microbiol. 2009; 11(10):2574-84.
• [3]Sokol H, Lay C, Seksik P, Tannock GW. Analysis of bacterial bowel communities of IBD patients: what has it revealed? Inflamm Bowel Dis. 2008; 14(6):858-67.
• [4]Kostic AD, Xavier RJ, Gevers D. The microbiome in inflammatory bowel disease: current status and the future ahead. Gastroenterology. 2014; 146(6):1489-99.
• [5]Rajilic-Stojanovic M, Biagi E, Heilig HG, Kajander K, Kekkonen RA, Tims S et al.. Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome. Gastroenterology. 2011; 141(5):1792-801.
• [6]Khan S, Chang L. Diagnosis and management of IBS. Nat Rev Gastroenterol Hepatol. 2010; 7(10):565-81.
• [7]Rana SV, Sharma S, Sinha SK, Parsad KK, Malik A, Singh K. Pro-inflammatory and anti-inflammatory cytokine response in diarrhoea-predominant irritable bowel syndrome patients. Trop Gastroenterol. 2012; 33(4):251-6.
• [8]Barbara G, Cremon C, Stanghellini V. Inflammatory bowel disease and irritable bowel syndrome: similarities and differences. Curr Opin Gastroenterol. 2014; 30(4):352-8.
• [9]Collins SM. Is the irritable gut an inflamed gut? Scand J Gastroenterol Suppl. 1992; 192:102-5.
• [10]Peterson J, Garges S, Giovanni M, McInnes P, Wang L, Schloss JA et al.. The NIH Human Microbiome Project. Genome Res. 2009; 19(12):2317-23.
• [11]Akiho H, Ihara E, Nakamura K. Low-grade inflammation plays a pivotal role in gastrointestinal dysfunction in irritable bowel syndrome. World J Gastrointest Pathophysiol. 2010; 1(3):97-105.
• [12]Vivinus-Nebot M, Frin-Mathy G, Bzioueche H, Dainese R, Bernard G, Anty R et al.. Functional bowel symptoms in quiescent inflammatory bowel diseases: role of epithelial barrier disruption and low-grade inflammation. Gut. 2014; 63(5):9.
• [13]Halpin SJ, Ford AC. Prevalence of symptoms meeting criteria for irritable bowel syndrome in inflammatory bowel disease: systematic review and meta-analysis. Am J Gastroenterol. 2012; 107(10):1474-82.
• [14]Simren M, Axelsson J, Gillberg R, Abrahamsson H, Svedlund J, Bjornsson ES. Quality of life in inflammatory bowel disease in remission: the impact of IBS-like symptoms and associated psychological factors. Am J Gastroenterol. 2002; 97(2):389-96.
• [15]Moss AC. The meaning of low-grade inflammation in clinically quiescent inflammatory bowel disease. Curr Opin Gastroenterol. 2014; 30(4):365-9.
• [16]Fries W, Belvedere A, Vetrano S. Sealing the broken barrier in IBD: intestinal permeability, epithelial cells and junctions. Curr Drug Targets. 2013; 14(12):1460-70.
• [17]Spiller R, Lam C. The shifting interface between IBS and IBD. Curr Opin Pharmacol. 2011; 11(6):586-92.
• [18]Edelblum KL, Turner JR. The tight junction in inflammatory disease: communication breakdown. Curr Opin Pharmacol. 2009; 9(6):715-20.
• [19]Lee BJ, Bak YT. Irritable bowel syndrome, gut microbiota and probiotics. J Neurogastroenterol Motil. 2011; 17(3):252-66.
• [20]DuPont AW, DuPont HL. The intestinal microbiota and chronic disorders of the gut. Nat Rev Gastroenterol Hepatol. 2011; 8(9):523-31.
• [21]Miquel S, Martin R, Rossi O, Bermudez-Humaran LG, Chatel JM, Sokol H, et al. Faecalibacterium prausnitzii and human intestinal health. Curr Opin Microbiol. 16(3):255–261.
• [22]Sokol H, Pigneur B, Watterlot L, Lakhdari O, Bermudez-Humaran LG, Gratadoux JJ et al.. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci U S A. 2008; 105(43):16731-6.
• [23]Miquel S, Martin R, Rossi O, Bermudez-Humaran L, Chatel J, Sokol H et al.. Faecalibacterium prausnitzii and human intestinal health. Curr Opin Microbiol. 2014; 16(3):255-61.
• [24]Varela E, Manichanh C, Gallart M, Torrejon A, Borruel N, Casellas F et al.. Colonisation by Faecalibacterium prausnitzii and maintenance of clinical remission in patients with ulcerative colitis. Aliment Pharmacol Ther. 2013; 38(2):151-61.
• [25]Martin R, Chain F, Miquel S, Lu J, Gratadoux JJ, Sokol H et al.. The commensal bacterium faecalibacterium prausnitzii Is protective in DNBS-induced chronic moderate and severe colitis models. Inflamm Bowel Dis. 2014; 20(3):417-20.
• [26]Ohman L, Simren M. New insights into the pathogenesis and pathophysiology of irritable bowel syndrome. Dig Liver Dis. 2007; 39(3):201-15.
• [27]Bonaz B. Inflammatory bowel diseases: a dysfunction of brain-gut interactions? Minerva Gastroenterol Dietol. 2013; 59(3):241-59.
• [28]Tornblom H, Abrahamsson H, Barbara G, Hellstrom PM, Lindberg G, Nyhlin H et al.. Inflammation as a cause of functional bowel disorders. Scand J Gastroenterol. 2005; 40(10):1140-8.
• [29]Bercik P, Collins SM, Verdu EF. Microbes and the gut-brain axis. Neurogastroenterol Motil. 2012; 24(5):405-13.
• [30]Bolino CM, Bercik P. Pathogenic factors involved in the development of irritable bowel syndrome: focus on a microbial role. Infect Dis Clin North Am. 2010; 24(4):961-75. ix
• [31]Clarke G, Cryan JF, Dinan TG, Quigley EM. Review article: probiotics for the treatment of irritable bowel syndrome–focus on lactic acid bacteria. Aliment Pharmacol Ther. 2012; 35(4):403-13.
• [32]Wrzosek L, Miquel S, Noordine ML, Bouet S, Joncquel Chevalier-Curt M, Robert V et al.. Bacteroides thetaiotaomicron and Faecalibacterium prausnitzii influence the production of mucus glycans and the development of goblet cells in the colonic epithelium of a gnotobiotic model rodent. BMC Biol. 2013; 11:61. BioMed Central Full Text
• [33]Qin HY, Xiao HT, Wu JC, Berman BM, Sung JJ, Bian ZX. Key factors in developing the trinitrobenzene sulfonic acid-induced post-inflammatory irritable bowel syndrome model in rats. World J Gastroenterol. 2012; 18(20):2481-92.
• [34]Wallace JL, Le T, Carter L, Appleyard CB, Beck PL. Hapten-induced chronic colitis in the rat: alternatives to trinitrobenzene sulfonic acid. J Pharmacol Toxicol Methods. 1995; 33(4):237-9.
• [35]Wang Y, Lam KS, Kraegen EW, Sweeney G, Zhang J, Tso AW et al.. Lipocalin-2 is an inflammatory marker closely associated with obesity, insulin resistance, and hyperglycemia in humans. Clin Chem. 2007; 53(1):34-41.
• [36]Shashidharamurthy R, Machiah D, Aitken JD, Putty K, Srinivasan G, Chassaing B et al.. Differential role of lipocalin 2 during immune complex-mediated acute and chronic inflammation in mice. Arthritis Rheum. 2013; 65(4):1064-73.
• [37]Vijay-Kumar M, Wu H, Jones R, Grant G, Babbin B, King TP et al.. Flagellin suppresses epithelial apoptosis and limits disease during enteric infection. Am J Pathol. 2006; 169(5):1686-700.
• [38]Suzuki T. Regulation of intestinal epithelial permeability by tight junctions. Cellular and molecular life sciences : CMLS. 2013; 70(4):631-59.
• [39]Tian T, Yu S, Ma D. Th22 and related cytokines in inflammatory and autoimmune diseases. Expert Opin Ther Targets. 2013; 17(2):113-25.
• [40]Van Dyken SJ, Locksley RM. Interleukin-4- and interleukin-13-mediated alternatively activated macrophages: roles in homeostasis and disease. Annu Rev Immunol. 2013; 31:317-43.
• [41]Sanchez-Munoz F, Dominguez-Lopez A, Yamamoto-Furusho JK. Role of cytokines in inflammatory bowel disease. World J Gastroenterol. 2008; 14(27):4280-8.
• [42]Luzina IG, Keegan AD, Heller NM, Rook GA, Shea-Donohue T, Atamas SP. Regulation of inflammation by interleukin-4: a review of “alternatives”. J Leukoc Biol. 2012; 92(4):753-64.
• [43]Al-Sadi R, Boivin M, Ma T. Mechanism of cytokine modulation of epithelial tight junction barrier. Front Biosci. 2009; 14:2765-78.
• [44]Capaldo CT, Nusrat A. Cytokine regulation of tight junctions. Biochim Biophys Acta. 2009; 1788(4):864-71.
• [45]Kiesslich R, Duckworth CA, Moussata D, Gloeckner A, Lim LG, Goetz M et al.. Local barrier dysfunction identified by confocal laser endomicroscopy predicts relapse in inflammatory bowel disease. Gut. 2012; 61(8):1146-53.
• [46]Carlsson AH, Yakymenko O, Olivier I, Hakansson F, Postma E, Keita AV et al.. Faecalibacterium prausnitzii supernatant improves intestinal barrier function in mice DSS colitis. Scand J Gastroenterol. 2013; 48(10):1136-44.
• [47]Talley NJ. Irritable bowel syndrome. Intern Med J. 2006; 36(11):724-8.
• [48]Coates MD, Johnson AC, Greenwood-Van Meerveld B, Mawe GM. Effects of serotonin transporter inhibition on gastrointestinal motility and colonic sensitivity in the mouse. Neurogastroenterol Motil. 2006; 18(6):464-71.
• [49]Khan WI, Ghia JE. Gut hormones: emerging role in immune activation and inflammation. Clin Exp Immunol. 2010; 161(1):19-27.
• [50]Bertrand PP, Barajas-Espinosa A, Neshat S, Bertrand RL, Lomax AE. Analysis of real-time serotonin (5-HT) availability during experimental colitis in mouse. Am J Physiol Gastrointest Liver Physiol. 2010; 298(3):G446-55.
• [51]Clarke G, Quigley EM, Cryan JF, Dinan TG. Irritable bowel syndrome: towards biomarker identification. Trends Mol Med. 2009; 15(10):478-89.
• [52]Spiller R. Serotonin and GI clinical disorders. Neuropharmacology. 2008; 55(6):1072-80.
• [53]Foley KF, Pantano C, Ciolino A, Mawe GM. IFN-gamma and TNF-alpha decrease serotonin transporter function and expression in Caco2 cells. Am J Physiol Gastrointest Liver Physiol. 2007; 292(3):G779-84.
• [54]Linden DR, Foley KF, McQuoid C, Simpson J, Sharkey KA, Mawe GM. Serotonin transporter function and expression are reduced in mice with TNBS-induced colitis. Neurogastroenterol Motil. 2005; 17(4):565-74.
• [55]Urdaci MC, Sanchez B. Some immunomodulatory effects of probiotic bacteria might be due to porcine neutrophil elastase inhibitor, a serpin present in MRS broth. Immunol Lett. 2009; 122(1):99-100.
• [56]Galipeau HJ, Rulli NE, Jury J, Huang X, Araya R, Murray JA et al.. Sensitization to gliadin induces moderate enteropathy and insulitis in nonobese diabetic-DQ8 mice. J Immunol. 2011; 187(8):4338-46.
• [57]Natividad JM, Huang X, Slack E, Jury J, Sanz Y, David C et al.. Host responses to intestinal microbial antigens in gluten-sensitive mice. PLoS One. 2009; 4(7):e6472.
• [58]Tambuwala MM, Cummins EP, Lenihan CR, Kiss J, Stauch M, Scholz CC et al.. Loss of prolyl hydroxylase-1 protects against colitis through reduced epithelial cell apoptosis and increased barrier function. Gastroenterology. 2010; 139(6):2093-101.
• [59]Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987; 162(1):156-9.