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      The Effects of Short-Chain Fatty Acids on Rat Colonic Hypermotility Induced by Water Avoidance Stress

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          Abstract

          Purpose

          Short-chain fatty acids (SCFAs) have been reported to play an important role in regulating gastrointestinal motility. The aim of this study is to investigate the possible role of SCFAs in water avoidance stress-induced colonic hypermotility.

          Methods

          A rat IBS model was established by water avoidance stress (WAS). Intestinal motility was assessed by fecal pellets expulsion. The fecal SCFA level was detected using gas chromatography-mass spectrometry (GC-MS). Western blotting was performed to assess the expression of SCFAs receptors. To determine the role of SCFAs in gut dysmotility, the rats of the WAS+SCFAS and SCFAs group were administrated with oral SCFAs. The colonic contractile activity was recorded with a RM6240 multichannel physiological signal system.

          Key Results

          WAS induced gastrointestinal hypermotility and increased defecation in rats. After repeated stress, the fecal SCFAs decreased significantly and the proportion of acetic acid, propionic acid, and butyric acid had changed from Control 2.6:1:1.5 to WAS 2:1:2.3. Protein levels of SCFAs receptors in the colon were promoted by WAS. In addition, oral SCFAs partly inhibited the colonic spontaneous motility both for SCFAs and WAS+SCFAs group in vivo. Meanwhile, we observed acetate had no effect on the contractile amplitudes of muscle strips, but it could slow down contractile frequency in a dose-dependent manner (1–100 mM). Propionate significantly inhibited the motor activity of colonic strips (1–30 mM). Butyrate inhibited the contractile amplitude of CM strips in a dose-dependent manner (1–30 mM), but for LM, it exhibited a stimulating effect at low concentrations of butyrate 1 mM–10 mM and was suppressed at high concentrations of 30 mM butyrate. Total SCFAs increased the contractile amplitude at low concentration (5–50 mM) and inhibited it at high concentration (50–150 mM). All SCFAs slowed down the frequency of colonic activity.

          Conclusion

          The stress-induced colonic hypermotility by WAS could be ameliorated through oral SCFA supplementation. SCFAs may have potential clinical therapeutic use in modulating gut motility.

          Most cited references46

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          The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon.

          The microbiome is being characterized by large-scale sequencing efforts, yet it is not known whether it regulates host metabolism in a general versus tissue-specific manner or which bacterial metabolites are important. Here, we demonstrate that microbiota have a strong effect on energy homeostasis in the colon compared to other tissues. This tissue specificity is due to colonocytes utilizing bacterially produced butyrate as their primary energy source. Colonocytes from germfree mice are in an energy-deprived state and exhibit decreased expression of enzymes that catalyze key steps in intermediary metabolism including the TCA cycle. Consequently, there is a marked decrease in NADH/NAD(+), oxidative phosphorylation, and ATP levels, which results in AMPK activation, p27(kip1) phosphorylation, and autophagy. When butyrate is added to germfree colonocytes, it rescues their deficit in mitochondrial respiration and prevents them from undergoing autophagy. The mechanism is due to butyrate acting as an energy source rather than as an HDAC inhibitor. Copyright © 2011 Elsevier Inc. All rights reserved.
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            The role of short-chain fatty acids in health and disease.

            There is now an abundance of evidence to show that short-chain fatty acids (SCFAs) play an important role in the maintenance of health and the development of disease. SCFAs are a subset of fatty acids that are produced by the gut microbiota during the fermentation of partially and nondigestible polysaccharides. The highest levels of SCFAs are found in the proximal colon, where they are used locally by enterocytes or transported across the gut epithelium into the bloodstream. Two major SCFA signaling mechanisms have been identified, inhibition of histone deacetylases (HDACs) and activation of G-protein-coupled receptors (GPCRs). Since HDACs regulate gene expression, inhibition of HDACs has a vast array of downstream consequences. Our understanding of SCFA-mediated inhibition of HDACs is still in its infancy. GPCRs, particularly GPR43, GPR41, and GPR109A, have been identified as receptors for SCFAs. Studies have implicated a major role for these GPCRs in the regulation of metabolism, inflammation, and disease. SCFAs have been shown to alter chemotaxis and phagocytosis; induce reactive oxygen species (ROS); change cell proliferation and function; have anti-inflammatory, antitumorigenic, and antimicrobial effects; and alter gut integrity. These findings highlight the role of SCFAs as a major player in maintenance of gut and immune homeostasis. Given the vast effects of SCFAs, and that their levels are regulated by diet, they provide a new basis to explain the increased prevalence of inflammatory disease in Westernized countries, as highlighted in this chapter.
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              Stress and Health: Psychological, Behavioral, and Biological Determinants

              Stressors have a major influence upon mood, our sense of well-being, behavior, and health. Acute stress responses in young, healthy individuals may be adaptive and typically do not impose a health burden. However, if the threat is unremitting, particularly in older or unhealthy individuals, the long-term effects of stressors can damage health. The relationship between psychosocial stressors and disease is affected by the nature, number, and persistence of the stressors as well as by the individual's biological vulnerability (i.e., genetics, constitutional factors), psychosocial resources, and learned patterns of coping. Psychosocial interventions have proven useful for treating stress-related disorders and may influence the course of chronic diseases.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                dddt
                dddt
                Drug Design, Development and Therapy
                Dove
                1177-8881
                02 November 2020
                2020
                : 14
                : 4671-4684
                Affiliations
                [1 ]Department of Gastroenterology, Renmin Hospital of Wuhan University , Wuhan, Hubei Province, People’s Republic of China
                [2 ]Key Laboratory of Hubei Province for Digestive System Diseases, Renmin Hospital of Wuhan University , Wuhan, Hubei Province, People’s Republic of China
                Author notes
                Correspondence: HeSheng Luo Email LHSxhnk@163.com
                [*]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0000-0002-0012-8835
                Article
                246619
                10.2147/DDDT.S246619
                7646441
                c0c0624e-067f-44de-b7ce-1bc9cb67b2c3
                © 2020 Yuan et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 19 January 2020
                : 24 September 2020
                Page count
                Figures: 7, Tables: 2, References: 46, Pages: 14
                Categories
                Original Research

                Pharmacology & Pharmaceutical medicine
                gastrointestinal motility,scfas,chronic stress,ibs
                Pharmacology & Pharmaceutical medicine
                gastrointestinal motility, scfas, chronic stress, ibs

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