The Triple Alliance: Microbiome, Mitochondria, and Metabolites in the Context of Age-Related Cognitive Decline and Alzheimer’s Disease

Abstract Alzheimer’s disease (AD) is a progressive, age-related neurodegenerative disorder that affects a large proportion of the older population. It currently lacks effective treatments, placing a heavy burden on patients, families, health care systems, and society. This is mainly due to our limit...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:The journals of gerontology. Series A, Biological sciences and medical sciences Biological sciences and medical sciences, 2023-12, Vol.78 (12), p.2187-2202
Hauptverfasser: Prajapati, Santosh K, Shah, Ria, Alford, Nicholas, Mishra, Sidharth P, Jain, Shalini, Hansen, Barbara, Sanberg, Paul, Molina, Anthony J A, Yadav, Hariom
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 2202
container_issue 12
container_start_page 2187
container_title The journals of gerontology. Series A, Biological sciences and medical sciences
container_volume 78
creator Prajapati, Santosh K
Shah, Ria
Alford, Nicholas
Mishra, Sidharth P
Jain, Shalini
Hansen, Barbara
Sanberg, Paul
Molina, Anthony J A
Yadav, Hariom
description Abstract Alzheimer’s disease (AD) is a progressive, age-related neurodegenerative disorder that affects a large proportion of the older population. It currently lacks effective treatments, placing a heavy burden on patients, families, health care systems, and society. This is mainly due to our limited comprehension of the pathophysiology of AD progression, as well as the lack of effective drug targets and intervention timing to address the underlying pathology. AD is a multifactorial condition, and emerging evidence suggests that abnormalities in the gut microbiota play a significant role as environmental and multifaceted contributors to AD, although the exact mechanisms are yet to be fully explored. Changes in the composition of microbiota influence host neuronal health through their metabolites. These metabolites regulate intestinal epithelia, blood-brain barrier permeability, and neuroinflammation by affecting mitochondrial function. The decline in the proportion of beneficial microbes and their essential metabolites during aging and AD is directly linked to poor mitochondrial function, although the specific mechanisms remain unclear. In this review, we discuss recent developments in understanding the impact of the microbiome and its metabolites on various cell types, their influence on the integrity of the gut and blood-brain barriers, systemic and brain inflammation, and cell-specific effects in AD pathology. This information is expected to pave the way for a new understanding of the interactions between microbiota and mitochondria in AD, providing a foundation for the development of novel treatments for AD.
doi_str_mv 10.1093/gerona/glad226
format Article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10692438</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><oup_id>10.1093/gerona/glad226</oup_id><sourcerecordid>2868118715</sourcerecordid><originalsourceid>FETCH-LOGICAL-c413t-7d7ab6f90c459404a5f8193e3e98b2306c92e01454ffd7fcf41076b1ce2520703</originalsourceid><addsrcrecordid>eNqFkc9u1DAQxiMEoqVw5YgscQGpaf0nThwuaLWlFKkVElokbpbjTLKuHHuxnQo4ceQVeD2epG53qYALc5mR_ZtPM_MVxVOCjwhu2fEIwTt1PFrVU1rfK_ZJw0XJGf90P9e4aUuOcb1XPIrxEt8Epw-LPdY0TNRU7Bc_VmtAq2A2FtDCWqOchlfowujgO-MnOMx18nrtXR-MOkTK9egCkuq8NQkiMg6lrLD0LsGXhPyAFiOUH8CqBH1-Hp1J5grQCWhrHNz2L-y3NZgJwq_vPyM6MRFUhMfFg0HZCE92-aD4ePpmtTwrz9-_fbdcnJe6IiyVTd-orh5arCveVrhSfBCkZcCgFR1luNYtBUwqXg1D3wx6qPIR6o5ooJziBrOD4vVWdzN3E_QaXArKyk0wkwpfpVdG_v3jzFqO_koSXLe0YiIrvNgpBP95hpjkZKIGa5UDP0dJRS0IEQ3hGX3-D3rp5-DyfpK22RdBKWaZOtpS-egxBhjupiFY3rgsty7Lncu54dmfO9zhv23NwMst4OfN_8SuAQJltW0</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2900682203</pqid></control><display><type>article</type><title>The Triple Alliance: Microbiome, Mitochondria, and Metabolites in the Context of Age-Related Cognitive Decline and Alzheimer’s Disease</title><source>MEDLINE</source><source>Oxford University Press Journals All Titles (1996-Current)</source><source>Alma/SFX Local Collection</source><creator>Prajapati, Santosh K ; Shah, Ria ; Alford, Nicholas ; Mishra, Sidharth P ; Jain, Shalini ; Hansen, Barbara ; Sanberg, Paul ; Molina, Anthony J A ; Yadav, Hariom</creator><contributor>Duque, Gustavo</contributor><creatorcontrib>Prajapati, Santosh K ; Shah, Ria ; Alford, Nicholas ; Mishra, Sidharth P ; Jain, Shalini ; Hansen, Barbara ; Sanberg, Paul ; Molina, Anthony J A ; Yadav, Hariom ; Duque, Gustavo</creatorcontrib><description>Abstract Alzheimer’s disease (AD) is a progressive, age-related neurodegenerative disorder that affects a large proportion of the older population. It currently lacks effective treatments, placing a heavy burden on patients, families, health care systems, and society. This is mainly due to our limited comprehension of the pathophysiology of AD progression, as well as the lack of effective drug targets and intervention timing to address the underlying pathology. AD is a multifactorial condition, and emerging evidence suggests that abnormalities in the gut microbiota play a significant role as environmental and multifaceted contributors to AD, although the exact mechanisms are yet to be fully explored. Changes in the composition of microbiota influence host neuronal health through their metabolites. These metabolites regulate intestinal epithelia, blood-brain barrier permeability, and neuroinflammation by affecting mitochondrial function. The decline in the proportion of beneficial microbes and their essential metabolites during aging and AD is directly linked to poor mitochondrial function, although the specific mechanisms remain unclear. In this review, we discuss recent developments in understanding the impact of the microbiome and its metabolites on various cell types, their influence on the integrity of the gut and blood-brain barriers, systemic and brain inflammation, and cell-specific effects in AD pathology. This information is expected to pave the way for a new understanding of the interactions between microbiota and mitochondria in AD, providing a foundation for the development of novel treatments for AD.</description><identifier>ISSN: 1079-5006</identifier><identifier>ISSN: 1758-535X</identifier><identifier>EISSN: 1758-535X</identifier><identifier>DOI: 10.1093/gerona/glad226</identifier><identifier>PMID: 37738628</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Aging ; Alzheimer Disease ; Alzheimer's disease ; Blood-brain barrier ; Brain ; Cognitive ability ; Cognitive Dysfunction ; Digestive system ; Gastrointestinal Microbiome ; Gastrointestinal tract ; Humans ; Inflammation ; Intestinal microflora ; Membrane permeability ; Metabolites ; Microbiomes ; Microbiota ; Mitochondria ; Nerve Degeneration ; Neurodegenerative diseases ; Pathology ; Pathophysiology ; THE JOURNAL OF GERONTOLOGY: Biological Sciences ; Therapeutic targets</subject><ispartof>The journals of gerontology. Series A, Biological sciences and medical sciences, 2023-12, Vol.78 (12), p.2187-2202</ispartof><rights>The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. 2023</rights><rights>The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.</rights><rights>Copyright Oxford University Press Dec 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c413t-7d7ab6f90c459404a5f8193e3e98b2306c92e01454ffd7fcf41076b1ce2520703</citedby><cites>FETCH-LOGICAL-c413t-7d7ab6f90c459404a5f8193e3e98b2306c92e01454ffd7fcf41076b1ce2520703</cites><orcidid>0000-0003-4504-1597</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,1584,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37738628$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Duque, Gustavo</contributor><creatorcontrib>Prajapati, Santosh K</creatorcontrib><creatorcontrib>Shah, Ria</creatorcontrib><creatorcontrib>Alford, Nicholas</creatorcontrib><creatorcontrib>Mishra, Sidharth P</creatorcontrib><creatorcontrib>Jain, Shalini</creatorcontrib><creatorcontrib>Hansen, Barbara</creatorcontrib><creatorcontrib>Sanberg, Paul</creatorcontrib><creatorcontrib>Molina, Anthony J A</creatorcontrib><creatorcontrib>Yadav, Hariom</creatorcontrib><title>The Triple Alliance: Microbiome, Mitochondria, and Metabolites in the Context of Age-Related Cognitive Decline and Alzheimer’s Disease</title><title>The journals of gerontology. Series A, Biological sciences and medical sciences</title><addtitle>J Gerontol A Biol Sci Med Sci</addtitle><description>Abstract Alzheimer’s disease (AD) is a progressive, age-related neurodegenerative disorder that affects a large proportion of the older population. It currently lacks effective treatments, placing a heavy burden on patients, families, health care systems, and society. This is mainly due to our limited comprehension of the pathophysiology of AD progression, as well as the lack of effective drug targets and intervention timing to address the underlying pathology. AD is a multifactorial condition, and emerging evidence suggests that abnormalities in the gut microbiota play a significant role as environmental and multifaceted contributors to AD, although the exact mechanisms are yet to be fully explored. Changes in the composition of microbiota influence host neuronal health through their metabolites. These metabolites regulate intestinal epithelia, blood-brain barrier permeability, and neuroinflammation by affecting mitochondrial function. The decline in the proportion of beneficial microbes and their essential metabolites during aging and AD is directly linked to poor mitochondrial function, although the specific mechanisms remain unclear. In this review, we discuss recent developments in understanding the impact of the microbiome and its metabolites on various cell types, their influence on the integrity of the gut and blood-brain barriers, systemic and brain inflammation, and cell-specific effects in AD pathology. This information is expected to pave the way for a new understanding of the interactions between microbiota and mitochondria in AD, providing a foundation for the development of novel treatments for AD.</description><subject>Aging</subject><subject>Alzheimer Disease</subject><subject>Alzheimer's disease</subject><subject>Blood-brain barrier</subject><subject>Brain</subject><subject>Cognitive ability</subject><subject>Cognitive Dysfunction</subject><subject>Digestive system</subject><subject>Gastrointestinal Microbiome</subject><subject>Gastrointestinal tract</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Intestinal microflora</subject><subject>Membrane permeability</subject><subject>Metabolites</subject><subject>Microbiomes</subject><subject>Microbiota</subject><subject>Mitochondria</subject><subject>Nerve Degeneration</subject><subject>Neurodegenerative diseases</subject><subject>Pathology</subject><subject>Pathophysiology</subject><subject>THE JOURNAL OF GERONTOLOGY: Biological Sciences</subject><subject>Therapeutic targets</subject><issn>1079-5006</issn><issn>1758-535X</issn><issn>1758-535X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc9u1DAQxiMEoqVw5YgscQGpaf0nThwuaLWlFKkVElokbpbjTLKuHHuxnQo4ceQVeD2epG53qYALc5mR_ZtPM_MVxVOCjwhu2fEIwTt1PFrVU1rfK_ZJw0XJGf90P9e4aUuOcb1XPIrxEt8Epw-LPdY0TNRU7Bc_VmtAq2A2FtDCWqOchlfowujgO-MnOMx18nrtXR-MOkTK9egCkuq8NQkiMg6lrLD0LsGXhPyAFiOUH8CqBH1-Hp1J5grQCWhrHNz2L-y3NZgJwq_vPyM6MRFUhMfFg0HZCE92-aD4ePpmtTwrz9-_fbdcnJe6IiyVTd-orh5arCveVrhSfBCkZcCgFR1luNYtBUwqXg1D3wx6qPIR6o5ooJziBrOD4vVWdzN3E_QaXArKyk0wkwpfpVdG_v3jzFqO_koSXLe0YiIrvNgpBP95hpjkZKIGa5UDP0dJRS0IEQ3hGX3-D3rp5-DyfpK22RdBKWaZOtpS-egxBhjupiFY3rgsty7Lncu54dmfO9zhv23NwMst4OfN_8SuAQJltW0</recordid><startdate>20231201</startdate><enddate>20231201</enddate><creator>Prajapati, Santosh K</creator><creator>Shah, Ria</creator><creator>Alford, Nicholas</creator><creator>Mishra, Sidharth P</creator><creator>Jain, Shalini</creator><creator>Hansen, Barbara</creator><creator>Sanberg, Paul</creator><creator>Molina, Anthony J A</creator><creator>Yadav, Hariom</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-4504-1597</orcidid></search><sort><creationdate>20231201</creationdate><title>The Triple Alliance: Microbiome, Mitochondria, and Metabolites in the Context of Age-Related Cognitive Decline and Alzheimer’s Disease</title><author>Prajapati, Santosh K ; Shah, Ria ; Alford, Nicholas ; Mishra, Sidharth P ; Jain, Shalini ; Hansen, Barbara ; Sanberg, Paul ; Molina, Anthony J A ; Yadav, Hariom</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c413t-7d7ab6f90c459404a5f8193e3e98b2306c92e01454ffd7fcf41076b1ce2520703</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Aging</topic><topic>Alzheimer Disease</topic><topic>Alzheimer's disease</topic><topic>Blood-brain barrier</topic><topic>Brain</topic><topic>Cognitive ability</topic><topic>Cognitive Dysfunction</topic><topic>Digestive system</topic><topic>Gastrointestinal Microbiome</topic><topic>Gastrointestinal tract</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Intestinal microflora</topic><topic>Membrane permeability</topic><topic>Metabolites</topic><topic>Microbiomes</topic><topic>Microbiota</topic><topic>Mitochondria</topic><topic>Nerve Degeneration</topic><topic>Neurodegenerative diseases</topic><topic>Pathology</topic><topic>Pathophysiology</topic><topic>THE JOURNAL OF GERONTOLOGY: Biological Sciences</topic><topic>Therapeutic targets</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Prajapati, Santosh K</creatorcontrib><creatorcontrib>Shah, Ria</creatorcontrib><creatorcontrib>Alford, Nicholas</creatorcontrib><creatorcontrib>Mishra, Sidharth P</creatorcontrib><creatorcontrib>Jain, Shalini</creatorcontrib><creatorcontrib>Hansen, Barbara</creatorcontrib><creatorcontrib>Sanberg, Paul</creatorcontrib><creatorcontrib>Molina, Anthony J A</creatorcontrib><creatorcontrib>Yadav, Hariom</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The journals of gerontology. Series A, Biological sciences and medical sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Prajapati, Santosh K</au><au>Shah, Ria</au><au>Alford, Nicholas</au><au>Mishra, Sidharth P</au><au>Jain, Shalini</au><au>Hansen, Barbara</au><au>Sanberg, Paul</au><au>Molina, Anthony J A</au><au>Yadav, Hariom</au><au>Duque, Gustavo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Triple Alliance: Microbiome, Mitochondria, and Metabolites in the Context of Age-Related Cognitive Decline and Alzheimer’s Disease</atitle><jtitle>The journals of gerontology. Series A, Biological sciences and medical sciences</jtitle><addtitle>J Gerontol A Biol Sci Med Sci</addtitle><date>2023-12-01</date><risdate>2023</risdate><volume>78</volume><issue>12</issue><spage>2187</spage><epage>2202</epage><pages>2187-2202</pages><issn>1079-5006</issn><issn>1758-535X</issn><eissn>1758-535X</eissn><abstract>Abstract Alzheimer’s disease (AD) is a progressive, age-related neurodegenerative disorder that affects a large proportion of the older population. It currently lacks effective treatments, placing a heavy burden on patients, families, health care systems, and society. This is mainly due to our limited comprehension of the pathophysiology of AD progression, as well as the lack of effective drug targets and intervention timing to address the underlying pathology. AD is a multifactorial condition, and emerging evidence suggests that abnormalities in the gut microbiota play a significant role as environmental and multifaceted contributors to AD, although the exact mechanisms are yet to be fully explored. Changes in the composition of microbiota influence host neuronal health through their metabolites. These metabolites regulate intestinal epithelia, blood-brain barrier permeability, and neuroinflammation by affecting mitochondrial function. The decline in the proportion of beneficial microbes and their essential metabolites during aging and AD is directly linked to poor mitochondrial function, although the specific mechanisms remain unclear. In this review, we discuss recent developments in understanding the impact of the microbiome and its metabolites on various cell types, their influence on the integrity of the gut and blood-brain barriers, systemic and brain inflammation, and cell-specific effects in AD pathology. This information is expected to pave the way for a new understanding of the interactions between microbiota and mitochondria in AD, providing a foundation for the development of novel treatments for AD.</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>37738628</pmid><doi>10.1093/gerona/glad226</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0003-4504-1597</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1079-5006
ispartof The journals of gerontology. Series A, Biological sciences and medical sciences, 2023-12, Vol.78 (12), p.2187-2202
issn 1079-5006
1758-535X
1758-535X
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10692438
source MEDLINE; Oxford University Press Journals All Titles (1996-Current); Alma/SFX Local Collection
subjects Aging
Alzheimer Disease
Alzheimer's disease
Blood-brain barrier
Brain
Cognitive ability
Cognitive Dysfunction
Digestive system
Gastrointestinal Microbiome
Gastrointestinal tract
Humans
Inflammation
Intestinal microflora
Membrane permeability
Metabolites
Microbiomes
Microbiota
Mitochondria
Nerve Degeneration
Neurodegenerative diseases
Pathology
Pathophysiology
THE JOURNAL OF GERONTOLOGY: Biological Sciences
Therapeutic targets
title The Triple Alliance: Microbiome, Mitochondria, and Metabolites in the Context of Age-Related Cognitive Decline and Alzheimer’s Disease
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-20T02%3A12%3A33IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20Triple%20Alliance:%20Microbiome,%20Mitochondria,%20and%20Metabolites%20in%20the%20Context%20of%20Age-Related%20Cognitive%20Decline%20and%20Alzheimer%E2%80%99s%20Disease&rft.jtitle=The%20journals%20of%20gerontology.%20Series%20A,%20Biological%20sciences%20and%20medical%20sciences&rft.au=Prajapati,%20Santosh%20K&rft.date=2023-12-01&rft.volume=78&rft.issue=12&rft.spage=2187&rft.epage=2202&rft.pages=2187-2202&rft.issn=1079-5006&rft.eissn=1758-535X&rft_id=info:doi/10.1093/gerona/glad226&rft_dat=%3Cproquest_pubme%3E2868118715%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2900682203&rft_id=info:pmid/37738628&rft_oup_id=10.1093/gerona/glad226&rfr_iscdi=true