Transplantation of a bacterial consortium ameliorates trinitrobenzenesulfonic acid-induced colitis and intestinal dysbiosis in rats
Abstract
Aim: To investigate the effects of a defined bacterial consortium on trinitrobenzenesulfonic acid (TNBS)-induced colitis and intestinal dysbiosis in rats. Materials & methods: Rats with TNBS-induced colitis were treated with ceftriaxone and/or a mixture of ten bacterial strains isolated from mouse feces for continuous 24 days. Macroscopic and histopathological parameters in colonic tissue were compared, as were myeloperoxidase enzyme activity and cytokine levels. Patterns of intestinal microbiota were assessed by PCR-denaturing gradient gel electrophoresis, the abundance of selected microbial groups was evaluated by qPCR. Results & conclusion: Transplantation of the bacterial consortium showed anti-inflammatory activity in the intestines of rats with TNBS-induced colitis and contributed to the rapid re-establishment of intestinal microbial equilibrium. A defined bacterial consortium may be a viable therapeutic option for the treatment inflammatory bowel disease.
Papers of special note have been highlighted as:•• of considerable interest
References
- 1 . Clinical epidemiology of inflammatory bowel disease: incidence, prevalence, and environmental influences. Gastroenterology 126, 1504–1517 (2004).
- 2 . Unravelling the pathogenesis of inflammatory bowel disease. Nature 448, 427–434 (2007).
- 3 A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis. Gut 63, 1275–1283 (2014). •• Shows that differences in gut microbiota exist between ulcerative colitis patients with healthy individuals.
- 4 The treatment-naive microbiome in new-onset Crohn's disease. Cell Host Microbe 15, 382–392 (2014).
- 5 Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491, 119–124 (2012).
- 6 An evidence-based systematic review on medical therapies for inflammatory bowel disease. Am. J. Gastroenterol. 106(Suppl. 1), S2–S25 (2011).
- 7 Antibiotics and probiotics in treatment of inflammatory bowel disease. World J. Gastroenterol. 12, 3306–3313 (2006).
- 8 . Fecal microbiota transplantation for the treatment of clostridium difficile infection: a systematic review. J. Clin. Gastroenterol. 48, 693–702 (2014).
- 9 . Fecal microbiota transplantation and emerging applications. Nat. Rev. Gastroenterol. Hepatol. 9, 88–96 (2012).
- 10 Duodenal infusion of donor feces for recurrent Clostridium difficile. N. Engl. J. Med. 368, 407–415 (2013).
- 11 Microbiota transplantation restores normal fecal bile acid composition in recurrent Clostridium difficile infection. Am. J. Physiol. Gastrointest. Liver. Physiol. 306, G310–G319 (2014).
- 12 Safety, tolerability, and clinical response after fecal transplantation in children and young adults with ulcerative colitis. J. Pediatr. Gastr. Nutr. 56, 597–601 (2013).
- 13 . Fecal microbiota transplantation inducing remission in crohn's colitis and the associated changes in fecal microbial profile. J. Clin. Gastroenterol. 48, 625–628 (2014).
- 14 . Manipulation of the microbiota for treatment of IBS and IBD – challenges and controversies. Gastroenterology 146, 1554–1563 (2014).
- 15 . Intestinal microbiota and faecal transplantation as treatment modality for insulin resistance and Type 2 diabetes mellitus. Clini. Exp. Immunol. 177, 24–29 (2014).
- 16 . Therapeutic potential of fecal microbiota transplantation. Gastroenterology 145, 946–953 (2013).
- 17 Fecal microbiota transplantation induces remission in patients with active ulcerative colitis in a randomized controlled trial. Gastroenterology 149, 102–109 (2015).
- 18 Fecal microbiota transplantation improves the quality of life in patients with inflammatory bowel disease. Gastroenterol. Res. Pract. 2015, 517–597 (2015).
- 19 Alteration of intestinal dysbiosis by fecal microbiota transplantation does not induce remission in patients with chronic active ulcerative colitis. Inflamm. Bowel Dis. 19, 2155–2165 (2013). •• Clinical research showed that manipulation of intestinal dysbiosis through fecal microbiota transplantation did not induce remission in patients with ulcerative colitis.
- 20 Temporal bacterial community dynamics vary among ulcerative colitis patients after fecal microbiota transplantation. Am. J. Gastroenterol. 108, 1620–1630 (2013).
- 21 . Patient attitudes toward the use of fecal microbiota transplantation in the treatment of recurrent Clostridium difficile infection. Clin. Infect. Dis. 55, 1652–1658 (2012).
- 22 Targeted restoration of the intestinal microbiota with a simple, defined bacteriotherapy resolves relapsing clostridium difficile disease in mice. PLoS Pathog. 8, e1002995 (2012). •• Animal study that shows that a bacterial consortium can resolve Clostridium difficile infection in mice.
- 23 . Bacteriotherapy for chronic relapsing Clostridium difficile diarrhoea in six patients. Lancet 1, 1156–1160 (1989).
- 24 Stool substitute transplant therapy for the eradication of Clostridium difficile infection: ‘repoopulating’ the gut. Microbiome 1, 3 (2013).
- 25 . From stool transplants to next-generation microbiota therapeutics. Gastroenterology 146, 1573–1582 (2014).
- 26 . The microbiome in inflammatory bowel disease and its modulation as a therapeutic manoeuvre. Proc. Nutr. Soci. 73, 452–456 (2014).
- 27 . New approaches for bacteriotherapy: prebiotics, new-generation probiotics, and synbiotics. Clin. Infect. Dis. 60(Suppl. 2), S108–S121 (2015).
- 28 . Intestinal microbiota and the efficacy of fecal microbiota transplantation in gastrointestinal disease. Gastroenterol. Hepatol. 10(4), 230–237 (2014).
- 29 . Probiotics in the management of inflammatory bowel disease. A systematic review of intervention studies in adult patients. Drugs 72(6), 803–823 (2012).
- 30 Fecal microbiota transplantation and bacterial consortium transplantation have comparable effects on the re-establishment of mucosal barrier function in mice with intestinal dysbiosis. Front. Microbiol. 6, 692 (2015). •• Our previous work suggested that bacterial consortium transplantation had comparable effects with fecal microbiota transplantation in re-establishing mucosal barrier functions in mice.
- 31 . Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology 96, 795–803 (1989).
- 32 . Effects of tumour necrosis factor-alpha synthesis inhibitors on rat trinitrobenzene sulphonic acid-induced chronic colitis. Eur. J. Pharmacol. 431, 103–110 (2001).
- 33 . Inhibition of dextran sulphate sodium (DSS)-induced colitis in mice by intracolonically administered antibodies against adhesion molecules (endothelial leucocyte adhesion molecule-1 (ELAM-1) or intercellular adhesion molecule-1 (ICAM-1)). Clin. Exp. Immunol. 117, 462–468 (1999).
- 34 High-throughput method for comparative analysis of denaturing gradient gel electrophoresis profiles from human fecal samples reveals significant increases in two bifidobacterial species after inulin-type prebiotic intake. FEMS Microbiol. Ecol. 75, 343–349 (2011).
- 35 Butyricicoccus pullicaecorum in inflammatory bowel disease. Gut 62, 1745–1752 (2013).
- 36 Assessment of the modulating effects of fructo-oligosaccarides on fecal microbiota using human flora-associated piglets. Arch. Microbiol. 192, 959–968 (2010).
- 37 . Intestinal Bacteria and Health: an Introductory Narrative. Harcourt Brace Jovanovich Japan, Tokyo, Japan (1978).
- 38 A modular organization of the human intestinal mucosal microbiota and its association with inflammatory bowel disease. PLoS ONE 8, e80702 (2013).
- 39 Microbial fingerprinting detects intestinal microbiota dysbiosis in zebrafish models with chemically-induced enterocolitis. BMC Microbiol. 13, 289 (2013).
- 40 . The gut microbiota in mouse models of inflammatory bowel disease. Front. Cell Infect. Microbiol. 4, 28 (2014).
- 41 Fecal microbial transplant effect on clinical outcomes and fecal microbiome in active crohn's disease. Inflamm. Bowel Dis. 21, 556–563 (2015).
- 42 The impact of the level of the intestinal short chain fatty acids in inflammatory bowel disease patients versus healthy subjects. Open Biochem. J. 4, 53–58 (2010).
- 43 Crosstalk between microbiota-derived short-chain fatty acids and intestinal epithelial HIF augments tissue barrier function. Cell Host Microbe 17, 662–671 (2015).
- 44 Commensal bacteroides species induce colitis in host-genotype-specific fashion in a mouse model of inflammatory bowel disease. Cell Host Microbe 9, 390–403 (2011).
- 45 Escherichia fergusonii bacteremia in a diabetic patient with pancreatic cancer. J. Clin. Microbiol. 49, 4001–4002 (2011).
- 46 Specific members of the predominant gut microbiota predict pouchitis following colectomy and IPAA in UC. Gut
doi:10.1136/gutjnl-2015-309398 (2015) (Epub ahead of print). - 47 Patterns of antibiotic exposure and clinical disease activity in inflammatory bowel disease: a 4-year prospective study. Inflamm. Bowel Dis. 21(11), 2576–2582 (2015). •• A prospective study showing that antibiotic exposure amplifies the intestinal dysbiosis in inflammatory bowel disease patients.
- 48 Lactobacillus GG prevents recurrence of colitis in HLA-b27 transgenic rats after antibiotic treatment. Gut 52, 370–376 (2003).
- 49 . Long-term impacts of antibiotic exposure on the human intestinal microbiota. Microbiology 156, 3216–3223 (2010).
- 50 Decreased diversity of the fecal microbiome in recurrent Clostridium difficile-associated diarrhea. J. Infect. Dis. 197, 435–438 (2008).
- 51 . Role of colonic short-chain fatty acid transport in diarrhea. Annu. Rev. Physiol. 72, 297–313 (2010).
- 52 . Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proc. Natl Acad. Sci. USA 108(Suppl. 1), 4554–4561 (2011).
- 53 Treg induction by a rationally selected mixture of clostridia strains from the human microbiota. Nature 500, 232–236 (2013).