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      Low-fat/high-fibre diet prehabilitation improves anastomotic healing via the microbiome: an experimental model : Diet and anastomotic healing after colonic surgery

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          Abstract

          Both obesity and the presence of collagenolytic bacterial strains ( Enterococcus faecalis ) can increase the risk of anastomotic leak. The aim of this study was to determine whether mice chronically fed a high-fat Western-type diet (WD) develop anastomotic leak in association with altered microbiota, and whether this can be mitigated by a short course of standard chow diet (SD; low fat/high fibre) before surgery. Male C57BL/6 mice were assigned to either SD or an obesogenic WD for 6 weeks followed by preoperative antibiotics and colonic anastomosis. Microbiota were analysed longitudinally after operation and correlated with healing using an established anastomotic healing score. In reiterative experiments, mice fed a WD for 6 weeks were exposed to a SD for 2, 4 and 6 days before colonic surgery, and anastomotic healing and colonic microbiota analysed. Compared with SD-fed mice, WD-fed mice demonstrated an increased risk of anastomotic leak, with a bloom in the abundance of Enterococcus in lumen and expelled stool (65–90 per cent for WD versus 4–15 per cent for SD; P = 0·010 for lumen, P = 0·013 for stool). Microbiota of SD-fed mice, but not those fed WD, were restored to their preoperative composition after surgery. Anastomotic healing was significantly improved when WD-fed mice were exposed to a SD diet for 2 days before antibiotics and surgery (P < 0·001). The adverse effects of chronic feeding of a WD on the microbiota and anastomotic healing can be prevented by a short course of SD in mice.

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          Most cited references25

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          The role and application of enterococci in food and health.

          The genus Enterococcus is the most controversial group of lactic acid bacteria. Studies on the microbiota of many traditional cheeses in the Mediterranean countries have indicated that enterococci play an important role in the ripening of these cheeses, probably through proteolysis, lipolysis, and citrate breakdown, hence contributing to their typical taste and flavour. Enterococci are also present in other fermented foods, such as sausages and olives. However, their role in these products has not been fully elucidated. Furthermore, the production of bacteriocins by enterococci is well documented. Moreover, enterococci are nowadays used as probiotics. At the same time, however, enterococci have been associated with a number of human infections. Several virulence factors have been described and the number of vancomycin-resistant enterococci is increasing. The controversial nature of enterococci has prompted an enormous increase in scientific papers and reviews in recent years, where researchers have been divided into two groups, namely pro and contra enterococci. To the authors' impression, the negative traits have been focused on very extensively. The aim of the present review is to give a balanced overview of both beneficial and virulence features of this divisive group of microorganisms, because it is only acquaintance with both sides that may allow their safe exploitation as starter cultures or co-cultures.
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            Collagen degradation and MMP9 activation by Enterococcus faecalis contribute to intestinal anastomotic leak.

            Even under the most expert care, a properly constructed intestinal anastomosis can fail to heal, resulting in leakage of its contents, peritonitis, and sepsis. The cause of anastomotic leak remains unknown, and its incidence has not changed in decades. We demonstrate that the commensal bacterium Enterococcus faecalis contributes to the pathogenesis of anastomotic leak through its capacity to degrade collagen and to activate tissue matrix metalloproteinase 9 (MMP9) in host intestinal tissues. We demonstrate in rats that leaking anastomotic tissues were colonized by E. faecalis strains that showed an increased collagen-degrading activity and also an increased ability to activate host MMP9, both of which contributed to anastomotic leakage. We demonstrate that the E. faecalis genes gelE and sprE were required for E. faecalis-mediated MMP9 activation. Either elimination of E. faecalis strains through direct topical antibiotics applied to rat intestinal tissues or pharmacological suppression of intestinal MMP9 activation prevented anastomotic leak in rats. In contrast, the standard recommended intravenous antibiotics used in patients undergoing colorectal surgery did not eliminate E. faecalis at anastomotic tissues nor did they prevent leak in our rat model. Finally, we show in humans undergoing colon surgery and treated with the standard recommended intravenous antibiotics that their anastomotic tissues still contained E. faecalis and other bacterial strains with collagen-degrading/MMP9-activating activity. We suggest that intestinal microbes with the capacity to produce collagenases and to activate host metalloproteinase MMP9 may break down collagen in the intestinal tissue contributing to anastomotic leak.
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              Risk Factors for Anastomotic Leak After Colon Resection for Cancer: Multivariate Analysis and Nomogram From a Multicentric, Prospective, National Study With 3193 Patients.

              To determine pre-/intraoperative risk factors for anastomotic leak after colon resection for cancer and to create a practical instrument for predicting anastomotic leak risk.
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                Author and article information

                Journal
                BJS
                British Journal of Surgery
                Br J Surg
                Wiley
                00071323
                December 26 2019
                Affiliations
                [1 ]Department of Surgery; University of Chicago; Chicago Illinois USA
                [2 ]Department of Surgery; Radboud University Medical Centre; Nijmegen the Netherlands
                Article
                10.1002/bjs.11388
                7875206
                31879948
                7b9aebe1-ab22-4b81-ae1d-7a7cf3826fc4
                © 2019

                http://doi.wiley.com/10.1002/tdm_license_1.1

                http://onlinelibrary.wiley.com/termsAndConditions#vor

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