Gut Online First, published on October 14, 2013 as 10.1136/gutjnl-2013-305799 Commentary

and maintenance of immunity such as 9 : a novel guilty regulatory T cell homeostasis. Although Gut: first published as 10.1136/gutjnl-2013-305799 on 14 October 2013. Downloaded from the concentrations of short-chain fatty player in ulcerative colitis acids (SCFA) were not significantly lower in the Machiels study in UC patients com- pathogenesis? pared with healthy controls, several other studies have shown that SCFA concentra- 1 2 Herbert Tilg, Silvio Danese tions are impaired in IBD patients. Surprisingly, the current knowledge of R hominis and especially its role in immun- Inflammatory bowel diseases (IBD) such as cytokines such as interleukin 12, interferon- ity and inflammation is very sparse and its Crohn’s disease (CD) or ulcerative colitis gamma, interleukin 2 or tumour necrosis potential role in intestinal inflammation 3 (UC) comprise the two most common factor-α. Whereas earlier studies demon- can only be speculated from one of its forms of intestinal inflammation charac- strated no major differences in the gut’s main properties, namely butyrate produc- terised by a chronic relapsing disease course. microbiota between healthy individuals and tion. Interestingly, iron availability might 4 The aetiology of both disorders has still patients with UC in remission, others affect Roseburia spp. concentrations as not yet been identified. Whereas it has observed marked differences between very low iron concentrations resulted in a been elegantly demonstrated in many healthy subjects and UC patients, especially decrease in Roseburia spp. in an in vitro 5 studies in the last years that genetic factors at the mucosal level. Besides the rather colonic fermentation model after inocula- are crucially involved, other so-called envir- well-established reduction of microbiota tion with immobilised faecal microbiota.10 onmental factors are much less well diversity in IBD patients, recent studies Intestinal iron availability is commonly defined.1 In recent years evidence was accu- have proposed a potential role for certain impaired in IBD patients and the relation- mulating that the gut microbiota and its such as Fusobacterium varium ship between iron stores and concentra- manipulation might constitute one of those strains as rather proinflammatory and detri- tions of R hominis in IBD patients would relevant ‘environmental’ factors. Trillions of mental, whereas other bacteria such as be another major interest of further microbes compose the intestinal microbiota F prausnitzii exert protective properties. studies. of healthy individuals and several studies Indeed, Fprausnitzii, a commensal under- Even though Machiels et al8 have repli- have demonstrated in the past that IBD represented in UC patients both during cated their findings of decreased R patients exhibit a pronounced dysbiosis. It active disease and in remission, shows hominis concentrations in UC patients in remains, however, speculative whether prominent anti-inflammatory activities in a second cohort,8 other studies so far observed changes are causally involved in vitro and in certain in vivo models.6 have failed to show this type of dysbiosis IBD pathogenesis or reflect simply epiphe- Importantly, it has been recently demon- in UC patients.45Only a small study nomena due to inflammation.2 strated that the recovery of Fprausnitzii described a reduction in Roseburia spp. in Whereas several clinical aspects strongly after disease relapse in UC patients was UC patients.11 Despite these challenging

support a role for intestinal bacteria in CD associated with maintenance of clinical and exciting data introducing a ‘poten- http://gut.bmj.com/ such as improvement of inflammation after remission.7 Overall, so far only a very few tially new player in UC’, several questions diversion of the faecal stream or improve- strains of the gut’s microbiota have been have to be addressed in the near future: ment of disease during antibiotic therapy, linked with a potential role in the pathogen- first of all, further clinical studies have to 8 similar observations are mostly not available esis of UC. Machiels et al propose that confirm this association. In vitro studies for UC. However, other aspects are suggest- another member of the microbiota, that is, should mechanistically demonstrate how ing a role for bacteria in the pathogenesis Roseburia hominis, might play a role in UC. R hominis might affect mucosal cytokine of UC as, for example, abnormal In this large clinical trial where 127 UC cascades. Does R hominis also exert on October 1, 2021 by guest. Protected copyright. mucosal secretion of IgG antibodies against patients and 87 age-matched and sex- mainly anti-inflammatory activities similar certain commensals. Several preclinical and matched controls were studied, the main to F prausnitzii? Is the whole R hominis clinical studies have recently supported the microbial signature consisted of a decrease necessary or a simple antigen needed? notion that some bacterial strains such as in the butyrate-producing R hominis Preclinical animal experiments must Lactobacillus casei, Lactobacillus plan- and F prausnitzii, both members of the investigate their effects in various estab- tarum or Faecalibacterium prausnitzii are phylum, as assessed by denatur- lished models of experimental colitis and able to suppress the production of potent ing gradient gel electrophoresis and PCR finally if all these studies reveal promising proinflammatory cytokines or even induce confirmation, whereas other species typic- results the final ‘human proof’ for a role anti-inflammatory cytokines such as inter- ally being altered in CD remained of this interesting commensal in UC war- leukin 10, whereas others such as non- unaffected. Interestingly, both R hominis rants prospective clinical trials using a ‘R pathogenic Escherichia coli strongly and F prausnitzii were inversely correlated hominis probiotic’ as a novel potential stimulate the synthesis of proinflammatory with disease activity suggesting that their treatment option. depletion might negatively influence intes- Overall, evidence is increasing that a tinal inflammation. It remains, however, 1Department of Internal Medicine I, Gastroenterology, microbial signature exists differentiating Endocrinology & Metabolism, Medical University unclear whether other environmental the two forms of IBD from each other Innsbruck, Innsbruck, Austria; 2Department of factors such as dietary factors, certain medi- and from healthy individuals. Whether Gastroenterology, IBD Center, IRCCS Humanitas, cations and others might have affected these findings have any implications in Rozzano, Italy obtained results. Overall, R hominis might understanding disease pathogenesis or Correspondence to Professor Herbert Tilg, be added as another member of the micro- even affect treatment strategies remains to Department of Internal Medicine I, Gastroenterology, flora playing potentially a role in UC. Endocrinology & Metabolism, Medical University be investigated. Commensals and IBD are Innsbruck, 6020 Innsbruck, Austria; herbert.tilg@i-med. Butyrate-producing commensals are currently a fascinating and exciting topic, ac.at assumed to play a major role in gut health whether this promise will hold its

CopyrightTilg H, et al .ArticleGut Month author 2013 Vol 0(or No 0their employer) 2013. Produced by BMJ Publishing Group Ltd (& BSG) under licence.1 Commentary expectations will be clarified hopefully in REFERENCES 7 Varela E, Manichanh C, Gallart M, et al. Colonisation the next years. 1 Parkes M. Evidence from genetics for a role of by Faecalibacterium prausnitzii and maintenance of Gut: first published as 10.1136/gutjnl-2013-305799 on 14 October 2013. Downloaded from autophagy and innate immunity in IBD pathogenesis. clinical remission in patients with ulcerative colitis. – Competing interests None. Dig Dis 2012;30:330–3. Aliment Pharmacol Ther 2013;38:151 61. 2 Danese S, Fiocchi C. Ulcerative colitis. N Engl J Med 8 Machiels K, Joossens M, Sabino J, et al. A decrease Provenance and peer review Commissioned; 2011;365:1713–25. of the butyrate-producing species Roseburia hominis internally peer reviewed. 3 Hart AL, Lammers K, Brigidi P, et al. Modulation of and Faecalibacterium prausnitzii defines dysbiosis in To cite Tilg H, Danese S. Gut Published Online First: human dendritic cell phenotype and function by patients with ulcerative colitis. Gut Published [please include Day Month Year] doi:10.1136/gutjnl- probiotic bacteria. Gut 2004;53:1602–9. Online First: 10 Sep 2013. doi:10.1136/gutjnl- 2013-305799 4 Willing BP, Dicksved J, Halfvarson J, et al. 2013-304833 A pyrosequencing study in twins shows that 9 Smith PM, Howitt MR, Panikov N, et al. The Received 17 September 2013 gastrointestinal microbial profiles vary with microbial metabolites, short-chain fatty acids, Accepted 20 September 2013 inflammatory bowel disease phenotypes. regulate colonic Treg cell homeostasis. Science Gastroenterology 2010;139:1844–54.e1. 2013;341:569–73. 5 Lepage P, Hasler R, Spehlmann ME, et al. Twin study 10 Dostal A, Fehlbaum S, Chassard C, et al. Low iron indicates loss of interaction between microbiota and availability in continuous in vitro colonic mucosa of patients with ulcerative colitis. fermentations induces strong dysbiosis of the child Gastroenterology 2011;141:227–36. gut microbial consortium and a decrease in main 6 Sokol H, Pigneur B, Watterlot L, et al. metabolites. FEMS Microbiol Ecol 2013;83:161–75. Faecalibacterium prausnitzii is an anti-inflammatory 11 Rajilic-Stojanovic M, Shanahan F, Guarner F, et al. ▸ http://dx.doi.org/10.1136/gutjnl-2013-304833 commensal bacterium identified by gut microbiota Phylogenetic analysis of dysbiosis in ulcerative colitis analysis of Crohn disease patients. Proc Natl Acad during remission. Inflamm Bowel Dis Gut 2013;0:1–2. doi:10.1136/gutjnl-2013-305799 Sci USA 2008;105:16731–6. 2013;19:481–8. http://gut.bmj.com/ on October 1, 2021 by guest. Protected copyright.

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