Cargando…

Translocation of gut commensal bacteria to the brain

The gut-brain axis, a bidirectional signaling network between the intestine and the central nervous system, is crucial to the regulation of host physiology and inflammation. Recent advances suggest a strong correlation between gut dysbiosis and neurological diseases, however, relatively little is kn...

Descripción completa

Detalles Bibliográficos
Autores principales: Thapa, Manoj, Kumari, Anuradha, Chin, Chui-Yoke, Choby, Jacob E., Jin, Fengzhi, Bogati, Bikash, Chopyk, Daniel M., Koduri, Nitya, Pahnke, Andrew, Elrod, Elizabeth J., Burd, Eileen M., Weiss, David S., Grakoui, Arash
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10491268/
https://www.ncbi.nlm.nih.gov/pubmed/37693595
http://dx.doi.org/10.1101/2023.08.30.555630
_version_ 1785104025250693120
author Thapa, Manoj
Kumari, Anuradha
Chin, Chui-Yoke
Choby, Jacob E.
Jin, Fengzhi
Bogati, Bikash
Chopyk, Daniel M.
Koduri, Nitya
Pahnke, Andrew
Elrod, Elizabeth J.
Burd, Eileen M.
Weiss, David S.
Grakoui, Arash
author_facet Thapa, Manoj
Kumari, Anuradha
Chin, Chui-Yoke
Choby, Jacob E.
Jin, Fengzhi
Bogati, Bikash
Chopyk, Daniel M.
Koduri, Nitya
Pahnke, Andrew
Elrod, Elizabeth J.
Burd, Eileen M.
Weiss, David S.
Grakoui, Arash
author_sort Thapa, Manoj
collection PubMed
description The gut-brain axis, a bidirectional signaling network between the intestine and the central nervous system, is crucial to the regulation of host physiology and inflammation. Recent advances suggest a strong correlation between gut dysbiosis and neurological diseases, however, relatively little is known about how gut bacteria impact the brain. Here, we reveal that gut commensal bacteria can translocate directly to the brain when mice are fed an altered diet that causes dysbiosis and intestinal permeability, and that this also occurs without diet alteration in distinct murine models of neurological disease. The bacteria were not found in other systemic sites or the blood, but were detected in the vagus nerve. Unilateral cervical vagotomy significantly reduced the number of bacteria in the brain, implicating the vagus nerve as a conduit for translocation. The presence of bacteria in the brain correlated with microglial activation, a marker of neuroinflammation, and with neural protein aggregation, a hallmark of several neurodegenerative diseases. In at least one model, the presence of bacteria in the brain was reversible as a switch from high-fat to standard diet resulted in amelioration of intestinal permeability, led to a gradual loss of detectable bacteria in the brain, and reduced the number of neural protein aggregates. Further, in murine models of Alzheimer’s disease, Parkinson’s disease, and autism spectrum disorder, we observed gut dysbiosis, gut leakiness, bacterial translocation to the brain, and microglial activation. These data reveal a commensal bacterial translocation axis to the brain in models of diverse neurological diseases.
format Online
Article
Text
id pubmed-10491268
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Cold Spring Harbor Laboratory
record_format MEDLINE/PubMed
spelling pubmed-104912682023-09-09 Translocation of gut commensal bacteria to the brain Thapa, Manoj Kumari, Anuradha Chin, Chui-Yoke Choby, Jacob E. Jin, Fengzhi Bogati, Bikash Chopyk, Daniel M. Koduri, Nitya Pahnke, Andrew Elrod, Elizabeth J. Burd, Eileen M. Weiss, David S. Grakoui, Arash bioRxiv Article The gut-brain axis, a bidirectional signaling network between the intestine and the central nervous system, is crucial to the regulation of host physiology and inflammation. Recent advances suggest a strong correlation between gut dysbiosis and neurological diseases, however, relatively little is known about how gut bacteria impact the brain. Here, we reveal that gut commensal bacteria can translocate directly to the brain when mice are fed an altered diet that causes dysbiosis and intestinal permeability, and that this also occurs without diet alteration in distinct murine models of neurological disease. The bacteria were not found in other systemic sites or the blood, but were detected in the vagus nerve. Unilateral cervical vagotomy significantly reduced the number of bacteria in the brain, implicating the vagus nerve as a conduit for translocation. The presence of bacteria in the brain correlated with microglial activation, a marker of neuroinflammation, and with neural protein aggregation, a hallmark of several neurodegenerative diseases. In at least one model, the presence of bacteria in the brain was reversible as a switch from high-fat to standard diet resulted in amelioration of intestinal permeability, led to a gradual loss of detectable bacteria in the brain, and reduced the number of neural protein aggregates. Further, in murine models of Alzheimer’s disease, Parkinson’s disease, and autism spectrum disorder, we observed gut dysbiosis, gut leakiness, bacterial translocation to the brain, and microglial activation. These data reveal a commensal bacterial translocation axis to the brain in models of diverse neurological diseases. Cold Spring Harbor Laboratory 2023-09-01 /pmc/articles/PMC10491268/ /pubmed/37693595 http://dx.doi.org/10.1101/2023.08.30.555630 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Thapa, Manoj
Kumari, Anuradha
Chin, Chui-Yoke
Choby, Jacob E.
Jin, Fengzhi
Bogati, Bikash
Chopyk, Daniel M.
Koduri, Nitya
Pahnke, Andrew
Elrod, Elizabeth J.
Burd, Eileen M.
Weiss, David S.
Grakoui, Arash
Translocation of gut commensal bacteria to the brain
title Translocation of gut commensal bacteria to the brain
title_full Translocation of gut commensal bacteria to the brain
title_fullStr Translocation of gut commensal bacteria to the brain
title_full_unstemmed Translocation of gut commensal bacteria to the brain
title_short Translocation of gut commensal bacteria to the brain
title_sort translocation of gut commensal bacteria to the brain
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10491268/
https://www.ncbi.nlm.nih.gov/pubmed/37693595
http://dx.doi.org/10.1101/2023.08.30.555630
work_keys_str_mv AT thapamanoj translocationofgutcommensalbacteriatothebrain
AT kumarianuradha translocationofgutcommensalbacteriatothebrain
AT chinchuiyoke translocationofgutcommensalbacteriatothebrain
AT chobyjacobe translocationofgutcommensalbacteriatothebrain
AT jinfengzhi translocationofgutcommensalbacteriatothebrain
AT bogatibikash translocationofgutcommensalbacteriatothebrain
AT chopykdanielm translocationofgutcommensalbacteriatothebrain
AT kodurinitya translocationofgutcommensalbacteriatothebrain
AT pahnkeandrew translocationofgutcommensalbacteriatothebrain
AT elrodelizabethj translocationofgutcommensalbacteriatothebrain
AT burdeileenm translocationofgutcommensalbacteriatothebrain
AT weissdavids translocationofgutcommensalbacteriatothebrain
AT grakouiarash translocationofgutcommensalbacteriatothebrain