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      Caecal infusion of the short‐chain fatty acid propionate affects the microbiota and expression of inflammatory cytokines in the colon in a fistula pig model

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          Summary

          Short‐chain fatty acids ( SCFAs), particularly butyrate, are known to suppress inflammation, and regulate the gut bacterial ecology. However, little is known about propionate. We report here that propionate infusion in the caecum dramatically affected the structure of colonic microbiota of pigs based on 16s rRNA high‐throughput sequencing. Sixteen pig models were perfused with saline or sodium propionate by a fistula in the caecum. At d 28, all pigs were slaughtered for analysing bacterial metabolites, colonic microbiota and the expression of genes related to inflammation. The results showed that caecal infusion of sodium propionate increased the concentration of propionate and decreased the butyrate concentration in colonic content. For biogenic amines, the tyramine concentration was increased, while the concentration of cadaverine was decreased by infusion of sodium propionate. Furthermore, at the level of phylum, propionate increased the abundance of Bacteroidetes and reduced the abundance of Firmicutes. Prevotella and Bacteroides counts were increased, while Turicibacter abundance was decreased at the level of genus. Real‐time qPCR showed that the expression of NF‐κB and IL‐18 was upregulated by propionate infusion, whereas no significant differences were observed for the expression of other genes related to inflammatory processes. Taken together, these results provide a new evidence for the role of short‐chain fatty acid propionate on the composition of microbial community and inflammatory cytokines.

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          Most cited references26

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          Has the microbiota played a critical role in the evolution of the adaptive immune system?

          Although microbes have been classically viewed as pathogens, it is now well established that the majority of host-bacterial interactions are symbiotic. During development and into adulthood, gut bacteria shape the tissues, cells, and molecular profile of our gastrointestinal immune system. This partnership, forged over many millennia of coevolution, is based on a molecular exchange involving bacterial signals that are recognized by host receptors to mediate beneficial outcomes for both microbes and humans. We explore how specific aspects of the adaptive immune system are influenced by intestinal commensal bacteria. Understanding the molecular mechanisms that mediate symbiosis between commensal bacteria and humans may redefine how we view the evolution of adaptive immunity and consequently how we approach the treatment of numerous immunologic disorders.
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            Anti-inflammatory properties of the short-chain fatty acids acetate and propionate: a study with relevance to inflammatory bowel disease.

            To compare the anti-inflammatory properties of butyrate with two other SCFAs, namely acetate and propionate, which have less well-documented effects on inflammation. The effect of SCFAs on cytokine release from human neutrophils was studied with ELISA. SCFA-dependent modulation of NF-kappaB reporter activity was assessed in the human colon adenocarcinoma cell line, Colo320DM. Finally, the effect of SCFAs on gene expression and cytokine release, measured with RT-PCR and ELISA, respectively, was studied in mouse colon organ cultures established from colitic mice. Acetate, propionate and butyrate at 30 mmol/L decreased LPS-stimulated TNFalpha release from neutrophils, without affecting IL-8 protein release. All SCFAs dose dependently inhibited NF-kappaB reporter activity in Colo320DM cells. Propionate dose-dependently suppressed IL-6 mRNA and protein release from colon organ cultures and comparative studies revealed that propionate and butyrate at 30 mmol/L caused a strong inhibition of immune-related gene expression, whereas acetate was less effective. A similar inhibition was achieved with the proteasome inhibitor MG-132, but not the p38 MAPK inhibitor SB203580. All SCFAs decreased IL-6 protein release from organ cultures. In the present study propionate and butyrate were equipotent, whereas acetate was less effective, at suppressing NF-kappaB reporter activity, immune-related gene expression and cytokine release in vitro. Our findings suggest that propionate and acetate, in addition to butyrate, could be useful in the treatment of inflammatory disorders, including IBD.
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              Suppressive effect of short-chain fatty acids on production of proinflammatory mediators by neutrophils.

              Short chain fatty acids (SCFAs) are fermentation products of anaerobic bacteria. More than just being an important energy source for intestinal epithelial cells, these compounds are modulators of leukocyte function and potential targets for the development of new drugs. The aim of this study was to evaluate the effects of SCFAs (acetate, propionate and butyrate) on production of nitric oxide (NO) and proinflammatory cytokines [tumor necrosis factor α (TNF-α) and cytokine-induced neutrophil chemoattractant-2 (CINC-2αβ)] by rat neutrophils. The involvement of nuclear factor κB (NF-κB) and histone deacetylase (HDAC) was examined. The effect of butyrate was also investigated in vivo after oral administration of tributyrin (a pro-drug of butyrate). Propionate and butyrate diminished TNF-α, CINC-2αβ and NO production by LPS-stimulated neutrophils. We also observed that these fatty acids inhibit HDAC activity and NF-κB activation, which might be involved in the attenuation of the LPS response. Products of cyclooxygenase and 5-lipoxygenase are not involved in the effects of SCFAs as indicated by the results obtained with the inhibitors of these enzymes. The recruitment of neutrophils to the peritonium after intraperitoneal administration of a glycogen solution (1%) and the ex vivo production of cytokines and NO by neutrophils were attenuated in rats that previously received tributyrin. These results argue that this triglyceride may be effective in the treatment of inflammatory conditions. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                yukaifan@njau.edu.cn
                Journal
                Microb Biotechnol
                Microb Biotechnol
                10.1111/(ISSN)1751-7915
                MBT2
                Microbial Biotechnology
                John Wiley and Sons Inc. (Hoboken )
                1751-7915
                01 June 2018
                September 2018
                : 11
                : 5 , Thematic Issue on Microbiomes, Microbiota and Microbial Consortia ( doiID: 10.1111/mbt2.2018.11.issue-5 )
                : 859-868
                Affiliations
                [ 1 ] Laboratory of Gastrointestinal Microbiology Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health College of Animal Science and Technology Nanjing Agricultural University Nanjing 210095 China
                [ 2 ] National Center for International Research on Animal Gut Nutrition Nanjing Agricultural University Nanjing 210095 China
                Author notes
                [*] [* ]For correspondence. E‐mail yukaifan@ 123456njau.edu.cn ; Tel. +86 25 8439 5523; Fax +86 25 8439 5314.
                [†]

                These authors contributed equally to this work.

                Author information
                http://orcid.org/0000-0003-4828-8130
                http://orcid.org/0000-0002-5018-3744
                Article
                MBT213282
                10.1111/1751-7915.13282
                6116746
                29856120
                5e7b5d3e-8ede-40e6-942b-fbb24d7db243
                © 2018 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 19 September 2017
                : 25 April 2018
                : 26 April 2018
                Page count
                Figures: 7, Tables: 2, Pages: 10, Words: 5776
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 31501962
                Funded by: Fundamental Research Funds for the Central Universities
                Award ID: KYZ201535
                Award ID: KJQN201609
                Funded by: National Basic Research Program of China
                Award ID: 2013CB127300
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                mbt213282
                September 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.4.7.1 mode:remove_FC converted:03.09.2018

                Biotechnology
                Biotechnology

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