Cargando…

Overview of Brain-to-Gut Axis Exposed to Chronic CNS Bacterial Infection(s) and a Predictive Urinary Metabolic Profile of a Brain Infected by Mycobacterium tuberculosis

A new paradigm in neuroscience has recently emerged – the brain–gut axis (BGA). The contemporary focus in this paradigm has been gut → brain (“bottom-up”), in which the gut-microbiome, and its perturbations, affects one’s psychological state-of-mind and behavior, and is pivotal in neurodegenerative...

Descripción completa

Detalles Bibliográficos
Autores principales: Isaiah, Simon, Loots, Du Toit, Solomons, Regan, van der Kuip, Martijn, Tutu Van Furth, A. Marceline, Mason, Shayne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186443/
https://www.ncbi.nlm.nih.gov/pubmed/32372900
http://dx.doi.org/10.3389/fnins.2020.00296
_version_ 1783526951273627648
author Isaiah, Simon
Loots, Du Toit
Solomons, Regan
van der Kuip, Martijn
Tutu Van Furth, A. Marceline
Mason, Shayne
author_facet Isaiah, Simon
Loots, Du Toit
Solomons, Regan
van der Kuip, Martijn
Tutu Van Furth, A. Marceline
Mason, Shayne
author_sort Isaiah, Simon
collection PubMed
description A new paradigm in neuroscience has recently emerged – the brain–gut axis (BGA). The contemporary focus in this paradigm has been gut → brain (“bottom-up”), in which the gut-microbiome, and its perturbations, affects one’s psychological state-of-mind and behavior, and is pivotal in neurodegenerative disorders. The emerging brain → gut (“top-down”) concept, the subject of this review, proposes that dysfunctional brain health can alter the gut-microbiome. Feedback of this alternative bidirectional highway subsequently aggravates the neurological pathology. This paradigm shift, however, focuses upon non-communicable neurological diseases (progressive neuroinflammation). What of infectious diseases, in which pathogenic bacteria penetrate the blood–brain barrier and interact with the brain, and what is this effect on the BGA in bacterial infection(s) that cause chronic neuroinflammation? Persistent immune activity in the CNS due to chronic neuroinflammation can lead to irreversible neurodegeneration and neuronal death. The properties of cerebrospinal fluid (CSF), such as immunological markers, are used to diagnose brain disorders. But what of metabolic markers for such purposes? If a BGA exists, then chronic CNS bacterial infection(s) should theoretically be reflected in the urine. The premise here is that chronic CNS bacterial infection(s) will affect the gut-microbiome and that perturbed metabolism in both the CNS and gut will release metabolites into the blood that are filtered (kidneys) and excreted in the urine. Here we assess the literature on the effects of chronic neuroinflammatory diseases on the gut-microbiome caused by bacterial infection(s) of the CNS, in the context of information attained via metabolomics-based studies of urine. Furthermore, we take a severe chronic neuroinflammatory infectious disease – tuberculous meningitis (TBM), caused by Mycobacterium tuberculosis, and examine three previously validated CSF immunological biomarkers – vascular endothelial growth factor, interferon-gamma and myeloperoxidase – in terms of the expected changes in normal brain metabolism. We then model the downstream metabolic effects expected, predicting pivotal altered metabolic pathways that would be reflected in the urinary profiles of TBM subjects. Our cascading metabolic model should be adjustable to account for other types of CNS bacterial infection(s) associated with chronic neuroinflammation, typically prevalent, and difficult to distinguish from TBM, in the resource-constrained settings of poor communities.
format Online
Article
Text
id pubmed-7186443
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-71864432020-05-05 Overview of Brain-to-Gut Axis Exposed to Chronic CNS Bacterial Infection(s) and a Predictive Urinary Metabolic Profile of a Brain Infected by Mycobacterium tuberculosis Isaiah, Simon Loots, Du Toit Solomons, Regan van der Kuip, Martijn Tutu Van Furth, A. Marceline Mason, Shayne Front Neurosci Neuroscience A new paradigm in neuroscience has recently emerged – the brain–gut axis (BGA). The contemporary focus in this paradigm has been gut → brain (“bottom-up”), in which the gut-microbiome, and its perturbations, affects one’s psychological state-of-mind and behavior, and is pivotal in neurodegenerative disorders. The emerging brain → gut (“top-down”) concept, the subject of this review, proposes that dysfunctional brain health can alter the gut-microbiome. Feedback of this alternative bidirectional highway subsequently aggravates the neurological pathology. This paradigm shift, however, focuses upon non-communicable neurological diseases (progressive neuroinflammation). What of infectious diseases, in which pathogenic bacteria penetrate the blood–brain barrier and interact with the brain, and what is this effect on the BGA in bacterial infection(s) that cause chronic neuroinflammation? Persistent immune activity in the CNS due to chronic neuroinflammation can lead to irreversible neurodegeneration and neuronal death. The properties of cerebrospinal fluid (CSF), such as immunological markers, are used to diagnose brain disorders. But what of metabolic markers for such purposes? If a BGA exists, then chronic CNS bacterial infection(s) should theoretically be reflected in the urine. The premise here is that chronic CNS bacterial infection(s) will affect the gut-microbiome and that perturbed metabolism in both the CNS and gut will release metabolites into the blood that are filtered (kidneys) and excreted in the urine. Here we assess the literature on the effects of chronic neuroinflammatory diseases on the gut-microbiome caused by bacterial infection(s) of the CNS, in the context of information attained via metabolomics-based studies of urine. Furthermore, we take a severe chronic neuroinflammatory infectious disease – tuberculous meningitis (TBM), caused by Mycobacterium tuberculosis, and examine three previously validated CSF immunological biomarkers – vascular endothelial growth factor, interferon-gamma and myeloperoxidase – in terms of the expected changes in normal brain metabolism. We then model the downstream metabolic effects expected, predicting pivotal altered metabolic pathways that would be reflected in the urinary profiles of TBM subjects. Our cascading metabolic model should be adjustable to account for other types of CNS bacterial infection(s) associated with chronic neuroinflammation, typically prevalent, and difficult to distinguish from TBM, in the resource-constrained settings of poor communities. Frontiers Media S.A. 2020-04-21 /pmc/articles/PMC7186443/ /pubmed/32372900 http://dx.doi.org/10.3389/fnins.2020.00296 Text en Copyright © 2020 Isaiah, Loots, Solomons, van der Kuip, Tutu Van Furth and Mason. http://creativecommons.org/licenses/by/4.0/ 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.
spellingShingle Neuroscience
Isaiah, Simon
Loots, Du Toit
Solomons, Regan
van der Kuip, Martijn
Tutu Van Furth, A. Marceline
Mason, Shayne
Overview of Brain-to-Gut Axis Exposed to Chronic CNS Bacterial Infection(s) and a Predictive Urinary Metabolic Profile of a Brain Infected by Mycobacterium tuberculosis
title Overview of Brain-to-Gut Axis Exposed to Chronic CNS Bacterial Infection(s) and a Predictive Urinary Metabolic Profile of a Brain Infected by Mycobacterium tuberculosis
title_full Overview of Brain-to-Gut Axis Exposed to Chronic CNS Bacterial Infection(s) and a Predictive Urinary Metabolic Profile of a Brain Infected by Mycobacterium tuberculosis
title_fullStr Overview of Brain-to-Gut Axis Exposed to Chronic CNS Bacterial Infection(s) and a Predictive Urinary Metabolic Profile of a Brain Infected by Mycobacterium tuberculosis
title_full_unstemmed Overview of Brain-to-Gut Axis Exposed to Chronic CNS Bacterial Infection(s) and a Predictive Urinary Metabolic Profile of a Brain Infected by Mycobacterium tuberculosis
title_short Overview of Brain-to-Gut Axis Exposed to Chronic CNS Bacterial Infection(s) and a Predictive Urinary Metabolic Profile of a Brain Infected by Mycobacterium tuberculosis
title_sort overview of brain-to-gut axis exposed to chronic cns bacterial infection(s) and a predictive urinary metabolic profile of a brain infected by mycobacterium tuberculosis
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186443/
https://www.ncbi.nlm.nih.gov/pubmed/32372900
http://dx.doi.org/10.3389/fnins.2020.00296
work_keys_str_mv AT isaiahsimon overviewofbraintogutaxisexposedtochroniccnsbacterialinfectionsandapredictiveurinarymetabolicprofileofabraininfectedbymycobacteriumtuberculosis
AT lootsdutoit overviewofbraintogutaxisexposedtochroniccnsbacterialinfectionsandapredictiveurinarymetabolicprofileofabraininfectedbymycobacteriumtuberculosis
AT solomonsregan overviewofbraintogutaxisexposedtochroniccnsbacterialinfectionsandapredictiveurinarymetabolicprofileofabraininfectedbymycobacteriumtuberculosis
AT vanderkuipmartijn overviewofbraintogutaxisexposedtochroniccnsbacterialinfectionsandapredictiveurinarymetabolicprofileofabraininfectedbymycobacteriumtuberculosis
AT tutuvanfurthamarceline overviewofbraintogutaxisexposedtochroniccnsbacterialinfectionsandapredictiveurinarymetabolicprofileofabraininfectedbymycobacteriumtuberculosis
AT masonshayne overviewofbraintogutaxisexposedtochroniccnsbacterialinfectionsandapredictiveurinarymetabolicprofileofabraininfectedbymycobacteriumtuberculosis