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      The Gut Microbiota and Short-Chain Fatty Acids Profile in Postural Orthostatic Tachycardia Syndrome


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          Postural orthostatic tachycardia syndrome (POTS) is a devastating chronic form of orthostatic intolerance associated with excessive heart rate increase without hypotension during upright posture. POTS patients exhibit increased circulating norepinephrine levels with exaggerated sympathetic nervous system response upon standing. Emerging evidence suggests a role for the gut microbiome in cardiovascular disorders. However, the etiology of POTS and whether the gut microbiome plays a role are not fully elucidated. We assessed whether the gut microbiome and fecal short-chain fatty acids were different in POTS patients ( N = 25) compared to healthy control ( N = 23) women. Patients underwent hemodynamic measurements while supine and upon standing. Fecal samples were collected and analyzed using shotgun sequencing and Liquid Chromatography-High Resolution Mass Spectrometry and dietary habits were measured with a fitness application. We found that POTS patients in the standing position had higher circulating norepinephrine and epinephrine levels and increased heart rate. There were no differences in diet composition between groups. Of note dietary salt intake was also similar despite the fact that these patients are advised to consume a high salt diet. Alpha and beta diversity were similar between groups. We observed no differences in bacteria at the phylum levels or Firmicutes to Bacteroidetes ratio. We found no significant differences at the genus level, but observed trends in certain bacteria. Lachnoclostridium genus were higher in POTS when compared to the control group. On the other hand, Coprococcus and Coprobacter, were lower in POTS patients compared to controls. Although our KEGG metabolic pathways indicated differences related to short-chain fatty acids (SCFAs), we found that both POTS patients and healthy controls had similar levels of SCFAs. These results suggest POTs per se may have limited effects on gut microbiota composition and derived SCFAs. Further studies are needed to assess the role of the alterations observed at the genus level.

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          The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication

          A substantial body of evidence supports that the gut microbiota plays a pivotal role in the regulation of metabolic, endocrine and immune functions. In recent years, there has been growing recognition of the involvement of the gut microbiota in the modulation of multiple neurochemical pathways through the highly interconnected gut-brain axis. Although amazing scientific breakthroughs over the last few years have expanded our knowledge on the communication between microbes and their hosts, the underpinnings of microbiota-gut-brain crosstalk remain to be determined. Short-chain fatty acids (SCFAs), the main metabolites produced in the colon by bacterial fermentation of dietary fibers and resistant starch, are speculated to play a key role in neuro-immunoendocrine regulation. However, the underlying mechanisms through which SCFAs might influence brain physiology and behavior have not been fully elucidated. In this review, we outline the current knowledge about the involvement of SCFAs in microbiota-gut-brain interactions. We also highlight how the development of future treatments for central nervous system (CNS) disorders can take advantage of the intimate and mutual interactions of the gut microbiota with the brain by exploring the role of SCFAs in the regulation of neuro-immunoendocrine function.
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            The neuroactive potential of the human gut microbiota in quality of life and depression

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              Using MicrobiomeAnalyst for comprehensive statistical, functional, and meta-analysis of microbiome data

              MicrobiomeAnalyst is an easy-to-use, web-based platform for comprehensive analysis of common data outputs generated from current microbiome studies. It enables researchers and clinicians with little or no bioinformatics training to explore a wide variety of well-established methods for microbiome data processing, statistical analysis, functional profiling and comparison with public datasets or known microbial signatures. MicrobiomeAnalyst currently contains four modules: Marker-gene Data Profiling (MDP), Shotgun Data Profiling (SDP), Projection with Public Data (PPD), and Taxon Set Enrichment Analysis (TSEA). This protocol will first introduce the MDP module by providing a step-wise description of how to prepare, process and normalize data; perform community profiling; identify important features; and conduct correlation and classification analysis. We will then demonstrate how to perform predictive functional profiling and introduce several unique features of the SDP module for functional analysis. The last two sections will describe the key steps involved in using the PPD and TSEA modules for meta-analysis and visual exploration of the results. In summary, MicrobiomeAnalyst offers a one-stop shop that enables microbiome researchers to thoroughly explore their preprocessed microbiome data via intuitive web interfaces. The complete protocol can be executed in ~70 min.

                Author and article information

                Front Physiol
                Front Physiol
                Front. Physiol.
                Frontiers in Physiology
                Frontiers Media S.A.
                02 June 2022
                : 13
                : 879012
                Division of Clinical Pharmacology , Department of Medicine Vanderbilt University Medical Center and Department of Molecular Physiology and Biophysics , Vanderbilt University , Nashville, TN, United States
                Author notes

                Edited by: Karen-Anne McVey Neufeld, McMaster University, Canada

                Reviewed by: Francine Marques, Monash University, Australia

                Jasenka Zubcevic, University of Toledo, United States

                *Correspondence: Annet Kirabo, Annet.Kirabo@ 123456vumc.org ; Cyndya A. Shibao, Cyndya.shibao@ 123456vanderbilt.edu

                This article was submitted to Autonomic Neuroscience, a section of the journal Frontiers in Physiology

                Copyright © 2022 Ishimwe, Breier, Saleem, Kastner, Kirabo and Shibao.

                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.

                : 18 February 2022
                : 29 April 2022
                Funded by: National Heart, Lung, and Blood Institute , doi 10.13039/100000050;
                Original Research

                Anatomy & Physiology
                short-chain fatty acids,norepinephrine,hypotension,pots,gut microbiota
                Anatomy & Physiology
                short-chain fatty acids, norepinephrine, hypotension, pots, gut microbiota


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