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The gut microbiome: a key player in the complexity of amyotrophic lateral sclerosis (ALS)

BACKGROUND: Much progress has been made in mapping genetic abnormalities linked to amyotrophic lateral sclerosis (ALS), but the majority of cases still present with no known underlying cause. Furthermore, even in families with a shared genetic abnormality there is significant phenotypic variability,...

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Autores principales: Boddy, Sarah L., Giovannelli, Ilaria, Sassani, Matilde, Cooper-Knock, Johnathan, Snyder, Michael P., Segal, Eran, Elinav, Eran, Barker, Lynne A., Shaw, Pamela J., McDermott, Christopher J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816375/
https://www.ncbi.nlm.nih.gov/pubmed/33468103
http://dx.doi.org/10.1186/s12916-020-01885-3
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author Boddy, Sarah L.
Giovannelli, Ilaria
Sassani, Matilde
Cooper-Knock, Johnathan
Snyder, Michael P.
Segal, Eran
Elinav, Eran
Barker, Lynne A.
Shaw, Pamela J.
McDermott, Christopher J.
author_facet Boddy, Sarah L.
Giovannelli, Ilaria
Sassani, Matilde
Cooper-Knock, Johnathan
Snyder, Michael P.
Segal, Eran
Elinav, Eran
Barker, Lynne A.
Shaw, Pamela J.
McDermott, Christopher J.
author_sort Boddy, Sarah L.
collection PubMed
description BACKGROUND: Much progress has been made in mapping genetic abnormalities linked to amyotrophic lateral sclerosis (ALS), but the majority of cases still present with no known underlying cause. Furthermore, even in families with a shared genetic abnormality there is significant phenotypic variability, suggesting that non-genetic elements may modify pathogenesis. Identification of such disease-modifiers is important as they might represent new therapeutic targets. A growing body of research has begun to shed light on the role played by the gut microbiome in health and disease with a number of studies linking abnormalities to ALS. MAIN BODY: The microbiome refers to the genes belonging to the myriad different microorganisms that live within and upon us, collectively known as the microbiota. Most of these microbes are found in the intestines, where they play important roles in digestion and the generation of key metabolites including neurotransmitters. The gut microbiota is an important aspect of the environment in which our bodies operate and inter-individual differences may be key to explaining the different disease outcomes seen in ALS. Work has begun to investigate animal models of the disease, and the gut microbiomes of people living with ALS, revealing changes in the microbial communities of these groups. The current body of knowledge will be summarised in this review. Advances in microbiome sequencing methods will be highlighted, as their improved resolution now enables researchers to further explore differences at a functional level. Proposed mechanisms connecting the gut microbiome to neurodegeneration will also be considered, including direct effects via metabolites released into the host circulation and indirect effects on bioavailability of nutrients and even medications. CONCLUSION: Profiling of the gut microbiome has the potential to add an environmental component to rapidly advancing studies of ALS genetics and move research a step further towards personalised medicine for this disease. Moreover, should compelling evidence of upstream neurotoxicity or neuroprotection initiated by gut microbiota emerge, modification of the microbiome will represent a potential new avenue for disease modifying therapies. For an intractable condition with few current therapeutic options, further research into the ALS microbiome is of crucial importance.
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spelling pubmed-78163752021-01-21 The gut microbiome: a key player in the complexity of amyotrophic lateral sclerosis (ALS) Boddy, Sarah L. Giovannelli, Ilaria Sassani, Matilde Cooper-Knock, Johnathan Snyder, Michael P. Segal, Eran Elinav, Eran Barker, Lynne A. Shaw, Pamela J. McDermott, Christopher J. BMC Med Review BACKGROUND: Much progress has been made in mapping genetic abnormalities linked to amyotrophic lateral sclerosis (ALS), but the majority of cases still present with no known underlying cause. Furthermore, even in families with a shared genetic abnormality there is significant phenotypic variability, suggesting that non-genetic elements may modify pathogenesis. Identification of such disease-modifiers is important as they might represent new therapeutic targets. A growing body of research has begun to shed light on the role played by the gut microbiome in health and disease with a number of studies linking abnormalities to ALS. MAIN BODY: The microbiome refers to the genes belonging to the myriad different microorganisms that live within and upon us, collectively known as the microbiota. Most of these microbes are found in the intestines, where they play important roles in digestion and the generation of key metabolites including neurotransmitters. The gut microbiota is an important aspect of the environment in which our bodies operate and inter-individual differences may be key to explaining the different disease outcomes seen in ALS. Work has begun to investigate animal models of the disease, and the gut microbiomes of people living with ALS, revealing changes in the microbial communities of these groups. The current body of knowledge will be summarised in this review. Advances in microbiome sequencing methods will be highlighted, as their improved resolution now enables researchers to further explore differences at a functional level. Proposed mechanisms connecting the gut microbiome to neurodegeneration will also be considered, including direct effects via metabolites released into the host circulation and indirect effects on bioavailability of nutrients and even medications. CONCLUSION: Profiling of the gut microbiome has the potential to add an environmental component to rapidly advancing studies of ALS genetics and move research a step further towards personalised medicine for this disease. Moreover, should compelling evidence of upstream neurotoxicity or neuroprotection initiated by gut microbiota emerge, modification of the microbiome will represent a potential new avenue for disease modifying therapies. For an intractable condition with few current therapeutic options, further research into the ALS microbiome is of crucial importance. BioMed Central 2021-01-20 /pmc/articles/PMC7816375/ /pubmed/33468103 http://dx.doi.org/10.1186/s12916-020-01885-3 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Review
Boddy, Sarah L.
Giovannelli, Ilaria
Sassani, Matilde
Cooper-Knock, Johnathan
Snyder, Michael P.
Segal, Eran
Elinav, Eran
Barker, Lynne A.
Shaw, Pamela J.
McDermott, Christopher J.
The gut microbiome: a key player in the complexity of amyotrophic lateral sclerosis (ALS)
title The gut microbiome: a key player in the complexity of amyotrophic lateral sclerosis (ALS)
title_full The gut microbiome: a key player in the complexity of amyotrophic lateral sclerosis (ALS)
title_fullStr The gut microbiome: a key player in the complexity of amyotrophic lateral sclerosis (ALS)
title_full_unstemmed The gut microbiome: a key player in the complexity of amyotrophic lateral sclerosis (ALS)
title_short The gut microbiome: a key player in the complexity of amyotrophic lateral sclerosis (ALS)
title_sort gut microbiome: a key player in the complexity of amyotrophic lateral sclerosis (als)
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816375/
https://www.ncbi.nlm.nih.gov/pubmed/33468103
http://dx.doi.org/10.1186/s12916-020-01885-3
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