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      Higher Risk of Stroke Is Correlated With Increased Opportunistic Pathogen Load and Reduced Levels of Butyrate-Producing Bacteria in the Gut

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          Abstract

          Objective: Gut microbiota is a newly identified risk factor for stroke, and there are no large prospective studies linking the baseline gut microbiome to long-term risk of stroke. We present here the correlation between the gut microbiota and stroke risk in people with no prior stroke history.

          Methods: A total of 141 participants aged ≥60 years without prior history of stroke were recruited and divided into low-risk, medium-risk, and high-risk groups based on known risk factors and whether they were suffering from chronic diseases. The composition of their gut microbiomes was compared using 16S rRNA gene amplicon next-generation-sequencing and Quantitative Insights into Microbial Ecology (QIIME) analysis. Levels of fecal short-chain fatty acids were measured using gas chromatography.

          Results: We found that opportunistic pathogens (e.g., Enterobacteriaceae and Veillonellaceae) and lactate-producing bacteria (e.g., Bifidobacterium and Lactobacillus) were enriched, while butyrate-producing bacteria (e.g., Lachnospiraceae and Ruminococcaceae) were depleted, in the high-risk group compared to the low-risk group. Butyrate concentrations were also lower in the fecal samples obtained from the high-risk group than from the low-risk group. The concentrations of other short-chain fatty acids (e.g., acetate, propionate, isobutyrate, isovalerate, and valerate) in the gut were comparable among the three groups.

          Conclusion: Participants at high risk of stroke were characterized by the enrichment of opportunistic pathogens, low abundance of butyrate-producing bacteria, and reduced concentrations of fecal butyrate. More researches into the gut microbiota as a risk factor in stroke should be carried out in the near future.

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          Most cited references18

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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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            Host-derived nitrate boosts growth of E. coli in the inflamed gut.

            Changes in the microbial community structure are observed in individuals with intestinal inflammatory disorders. These changes are often characterized by a depletion of obligate anaerobic bacteria, whereas the relative abundance of facultative anaerobic Enterobacteriaceae increases. The mechanisms by which the host response shapes the microbial community structure, however, remain unknown. We show that nitrate generated as a by-product of the inflammatory response conferred a growth advantage to the commensal bacterium Escherichia coli in the large intestine of mice. Mice deficient in inducible nitric oxide synthase did not support the growth of E. coli by nitrate respiration, suggesting that the nitrate generated during inflammation was host-derived. Thus, the inflammatory host response selectively enhances the growth of commensal Enterobacteriaceae by generating electron acceptors for anaerobic respiration.
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              Butyrate, neuroepigenetics and the gut microbiome: Can a high fiber diet improve brain health?

              As interest in the gut microbiome has grown in recent years, attention has turned to the impact of our diet on our brain. The benefits of a high fiber diet in the colon have been well documented in epidemiological studies, but its potential impact on the brain has largely been understudied. Here, we will review evidence that butyrate, a short-chain fatty acid (SCFA) produced by bacterial fermentation of fiber in the colon, can improve brain health. Butyrate has been extensively studied as a histone deacetylase (HDAC) inhibitor but also functions as a ligand for a subset of G protein-coupled receptors and as an energy metabolite. These diverse modes of action make it well suited for solving the wide array of imbalances frequently encountered in neurological disorders. In this review, we will integrate evidence from the disparate fields of gastroenterology and neuroscience to hypothesize that the metabolism of a high fiber diet in the gut can alter gene expression in the brain to prevent neurodegeneration and promote regeneration.
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                Author and article information

                Contributors
                Journal
                Front Cell Infect Microbiol
                Front Cell Infect Microbiol
                Front. Cell. Infect. Microbiol.
                Frontiers in Cellular and Infection Microbiology
                Frontiers Media S.A.
                2235-2988
                04 February 2019
                2019
                : 9
                : 4
                Affiliations
                [1] 1Department of Neurology, Nanfang Hospital, Southern Medical University , Guangzhou, China
                [2] 2State Key Laboratory of Organ Failure Research, Microbiome Medicine Center, Division of Laboratory Medicine, Zhujiang Hospital, Southern Medical University , Guangzhou, China
                Author notes

                Edited by: Angela C. Poole, Cornell University, United States

                Reviewed by: David R. Jacobs, University of Minnesota Twin Cities, United States; Anna Heintz-Buschart, German Center for Integrative Biodiversity Research, Germany

                *Correspondence: Yan He 197053351@ 123456qq.com

                This article was submitted to Microbiome in Health and Disease, a section of the journal Frontiers in Cellular and Infection Microbiology

                †These authors have contributed equally to this work and share first authorship

                ‡These authors share last authorship

                Article
                10.3389/fcimb.2019.00004
                6369648
                30778376
                369e28d7-c673-4a33-a79d-30fbfbcbf4a1
                Copyright © 2019 Zeng, Gao, Peng, Wu, Zhu, Tan, Xia, You, Xu, Pan, Zhou, He and Yin.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 04 October 2018
                : 09 January 2019
                Page count
                Figures: 4, Tables: 2, Equations: 0, References: 50, Pages: 12, Words: 8738
                Categories
                Cellular and Infection Microbiology
                Original Research

                Infectious disease & Microbiology
                stroke risk,fecal,microbiota,16s rrna,short-chain fatty acids
                Infectious disease & Microbiology
                stroke risk, fecal, microbiota, 16s rrna, short-chain fatty acids

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