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      Fecal microbiota transplantation decreases intestinal loads of multi-drug resistant Pseudomonas aeruginosa in murine carriers

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          Abstract

          Intestinal carriage of multi-drug resistant (MDR) Gram-negative bacteria including Pseudomonas aeruginosa (Psae) constitutes a pivotal prerequisite for subsequent fatal endogenous infections in patients at risk. We here addressed whether fecal microbiota transplantation (FMT) could effectively combat MDR-Psae carriage. Therefore, secondary abiotic mice were challenged with MDR-Psae by gavage. One week later, mice were subjected to peroral FMT from either murine or human donors on 3 consecutive days. Irrespective of murine or human origin of fecal transplant, intestinal MDR-Psae loads decreased as early as 24 h after the initial FMT. Remarkably, the murine FMT could lower intestinal MDR-Psae burdens by approximately 4 log orders of magnitude within 1 week. In another intervention study, mice harboring a human gut microbiota were perorally challenged with MDR-Psae and subjected to murine FMT on 3 consecutive days, 1 week later. Strikingly, within 5 days, murine FMT resulted in lower loads and carrier rates of MDR-Psae in mice with a human gut microbiota. In conclusion, FMT might be a promising antibiotics-independent option to combat intestinal MDR-Psae carriage and thus prevent from future endogenous infections of patients at risk.

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          Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis

          The spread of antibiotic-resistant bacteria poses a substantial threat to morbidity and mortality worldwide. Due to its large public health and societal implications, multidrug-resistant tuberculosis has been long regarded by WHO as a global priority for investment in new drugs. In 2016, WHO was requested by member states to create a priority list of other antibiotic-resistant bacteria to support research and development of effective drugs.
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            Colonic health: fermentation and short chain fatty acids.

            Interest has been recently rekindled in short chain fatty acids (SCFAs) with the emergence of prebiotics and probiotics aimed at improving colonic and systemic health. Dietary carbohydrates, specifically resistant starches and dietary fiber, are substrates for fermentation that produce SCFAs, primarily acetate, propionate, and butyrate, as end products. The rate and amount of SCFA production depends on the species and amounts of microflora present in the colon, the substrate source and gut transit time. SCFAs are readily absorbed. Butyrate is the major energy source for colonocytes. Propionate is largely taken up by the liver. Acetate enters the peripheral circulation to be metabolized by peripheral tissues. Specific SCFA may reduce the risk of developing gastrointestinal disorders, cancer, and cardiovascular disease. Acetate is the principal SCFA in the colon, and after absorption it has been shown to increase cholesterol synthesis. However, propionate, a gluconeogenerator, has been shown to inhibit cholesterol synthesis. Therefore, substrates that can decrease the acetate: propionate ratio may reduce serum lipids and possibly cardiovascular disease risk. Butyrate has been studied for its role in nourishing the colonic mucosa and in the prevention of cancer of the colon, by promoting cell differentiation, cell-cycle arrest and apoptosis of transformed colonocytes; inhibiting the enzyme histone deacetylase and decreasing the transformation of primary to secondary bile acids as a result of colonic acidification. Therefore, a greater increase in SCFA production and potentially a greater delivery of SCFA, specifically butyrate, to the distal colon may result in a protective effect. Butyrate irrigation (enema) has also been suggested in the treatment of colitis. More human studies are now needed, especially, given the diverse nature of carbohydrate substrates and the SCFA patterns resulting from their fermentation. Short-term and long-term human studies are particularly required on SCFAs in relation to markers of cancer risk. These studies will be key to the success of dietary recommendations to maximize colonic disease prevention.
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              Bacteriocin production as a mechanism for the antiinfective activity of Lactobacillus salivarius UCC118.

              The mechanisms by which probiotic strains enhance the health of the host remain largely uncharacterized. Here we demonstrate that Lactobacillus salivarius UCC118, a recently sequenced and genetically tractable probiotic strain of human origin, produces a bacteriocin in vivo that can significantly protect mice against infection with the invasive foodborne pathogen Listeria monocytogenes. A stable mutant of Lb. salivarius UCC118 that is unable to produce the Abp118 bacteriocin also failed to protect mice against infection with two strains of L. monocytogenes, EGDe and LO28, confirming that bacteriocin production is the primary mediator of protection against this organism. Furthermore, Lb. salivarius UCC118 did not offer any protection when mice were infected with a strain of L. monocytogenes expressing the cognate Abp118 immunity protein AbpIM, confirming that the antimicrobial effect is a result of direct antagonism between Lb. salivarius and the pathogen, mediated by the bacteriocin Abp118.
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                Author and article information

                Journal
                1886
                European Journal of Microbiology and Immunology
                Akadémiai Kiadó
                2062-8633
                March 2019
                : 9
                : 1
                : 14-22
                Affiliations
                [1]Institute of Microbiology, Infectious Diseases and Immunology, Gastrointestinal Microbiology Research Group, Charité – University Medicine Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health , Berlin, Germany
                Author notes
                [*]

                Author for correspondence: Charité – University Medicine Berlin, CC5, Department of Microbiology, Infectious Diseases and Immunology, Campus Benjamin Franklin, FEM, Garystr. 5, D-14195 Berlin, Germany; markus.heimesaat@ 123456charite.de ; Tel: +49-30-450524318.

                Article
                10.1556/1886.2019.00002
                6444800
                30967971
                1d4e21bb-25ef-4774-ae35-d3dd6620035c
                © 2019 The Author(s)

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and reproduction in any medium for non-commercial purposes, provided the original author and source are credited, a link to the CC License is provided, and changes - if any - are indicated.

                History
                : 14 January 2019
                : 2 February 2019
                : 4 March 2019
                Page count
                Pages: 9
                Categories
                Original Research Paper

                Medicine,Immunology,Public health,Microbiology & Virology,Infectious disease & Microbiology
                human microbiota associated mice,pro-inflammatory immune responses,Multi-drug resistant Pseudomonas aeruginosa ,fecal microbiota transplantation,intestinal multi-drug resistant Gram-negative bacterial carriage,antibiotics-independent intervention strategies,host-pathogen-interaction

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