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      Gut Microbiota and Acute Diverticulitis: Role of Probiotics in Management of This Delicate Pathophysiological Balance

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          Abstract

          How can the knowledge of probiotics and their mechanisms of action be translated into clinical practice when treating patients with diverticular disease and acute diverticulitis? Changes in microbiota composition have been observed in patients who were developing acute diverticulitis, with a reduction of taxa with anti-inflammatory activity, such as Clostridium cluster IV, Lactobacilli and Bacteroides. Recent observations supported that a dysbiosis characterised by decreased presence of anti-inflammatory bacterial species might be linked to mucosal inflammation, and a vicious cycle results from a mucosal inflammation driving dysbiosis at the same time. An alteration in gut microbiota can lead to an altered activation of nerve fibres, and subsequent neuronal and muscular dysfunction, thus favoring abdominal symptoms’ development. The possible role of dysbiosis and mucosal inflammation in leading to dysmotility is linked, in turn, to bacterial translocation from the lumen of the diverticulum to perivisceral area. There, a possible activation of Toll-like receptors has been described, with a subsequent inflammatory reaction at the level of the perivisceral tissues. Being aware that bacterial colonisation of diverticula is involved in the pathogenesis of acute diverticulitis, the rationale for the potential role of probiotics in the treatment of this disease becomes clearer. For this review, articles were identified using the electronic PubMed database through a comprehensive search conducted by combining key terms such as “gut microbiota”, “probiotics and gut disease”, “probiotics and acute diverticulitis”, “probiotics and diverticular disease”, “probiotics mechanism of action”. However, the amount of data present on this matter is not sufficient to draw robust conclusions on the efficacy of probiotics for symptoms’ management in diverticular disease.

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          Most cited references64

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          Role of the microbiota in immunity and inflammation.

          The microbiota plays a fundamental role on the induction, training, and function of the host immune system. In return, the immune system has largely evolved as a means to maintain the symbiotic relationship of the host with these highly diverse and evolving microbes. When operating optimally, this immune system-microbiota alliance allows the induction of protective responses to pathogens and the maintenance of regulatory pathways involved in the maintenance of tolerance to innocuous antigens. However, in high-income countries, overuse of antibiotics, changes in diet, and elimination of constitutive partners, such as nematodes, may have selected for a microbiota that lack the resilience and diversity required to establish balanced immune responses. This phenomenon is proposed to account for some of the dramatic rise in autoimmune and inflammatory disorders in parts of the world where our symbiotic relationship with the microbiota has been the most affected. Copyright © 2014 Elsevier Inc. All rights reserved.
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            Induction of colonic regulatory T cells by indigenous Clostridium species.

            CD4(+) T regulatory cells (T(regs)), which express the Foxp3 transcription factor, play a critical role in the maintenance of immune homeostasis. Here, we show that in mice, T(regs) were most abundant in the colonic mucosa. The spore-forming component of indigenous intestinal microbiota, particularly clusters IV and XIVa of the genus Clostridium, promoted T(reg) cell accumulation. Colonization of mice by a defined mix of Clostridium strains provided an environment rich in transforming growth factor-β and affected Foxp3(+) T(reg) number and function in the colon. Oral inoculation of Clostridium during the early life of conventionally reared mice resulted in resistance to colitis and systemic immunoglobulin E responses in adult mice, suggesting a new therapeutic approach to autoimmunity and allergy.
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              The Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota.

              Mucosal surfaces constantly encounter microbes. Toll-like receptors (TLRs) mediate recognition of microbial patterns to eliminate pathogens. By contrast, we demonstrate that the prominent gut commensal Bacteroides fragilis activates the TLR pathway to establish host-microbial symbiosis. TLR2 on CD4(+) T cells is required for B. fragilis colonization of a unique mucosal niche in mice during homeostasis. A symbiosis factor (PSA, polysaccharide A) of B. fragilis signals through TLR2 directly on Foxp3(+) regulatory T cells to promote immunologic tolerance. B. fragilis lacking PSA is unable to restrain T helper 17 cell responses and is defective in niche-specific mucosal colonization. Therefore, commensal bacteria exploit the TLR pathway to actively suppress immunity. We propose that the immune system can discriminate between pathogens and the microbiota through recognition of symbiotic bacterial molecules in a process that engenders commensal colonization.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                J Pers Med
                J Pers Med
                jpm
                Journal of Personalized Medicine
                MDPI
                2075-4426
                14 April 2021
                April 2021
                : 11
                : 4
                : 298
                Affiliations
                [1 ]Emergency Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, 1-00168 Rome, Italy; marcello.covino@ 123456policlinicogemelli.it (M.C.); marcello.candelli@ 123456policlinicogemelli.it (M.C.); veronica.ojetti@ 123456unicatt.it (V.O.); francesco.franceschi@ 123456unicatt.it (F.F.)
                [2 ]Università Cattolica del Sacro Cuore, 1-00168 Rome, Italy; laura.franza@ 123456policlicnigemelli.it (L.F.); christian.zanza@ 123456live.it (C.Z.); rikho88@ 123456gmail.com (E.T.); martina.petrucci@ 123456policlinicogemelli.it (M.P.); rebecca.nicolo@ 123456policlinicogemelli.it (R.N.); saviange@ 123456libero.it (A.S.)
                [3 ]Unit of Gastroenterology, Department of Systems Medicine, Tor Vergata University, 2-00133 Rome, Italy; mattiabrigida@ 123456hotmail.it
                Author notes
                Author information
                https://orcid.org/0000-0001-5703-8737
                https://orcid.org/0000-0001-8443-7880
                Article
                jpm-11-00298
                10.3390/jpm11040298
                8070761
                33919818
                1e898ae5-3d9e-4256-a450-feea835f02cc
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 20 February 2021
                : 11 April 2021
                Categories
                Review

                gut microbiota,probiotics and gut disease,probiotics and acute diverticulitis,probiotics and diverticular disease,probiotics mechanism of action

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