Disruptions of Anaerobic Gut Bacteria Are Associated with Stroke and Post-stroke Infection: a Prospective Case–Control Study
In recent years, preclinical studies have illustrated the potential role of intestinal bacterial composition in the risk of stroke and post-stroke infections. The results of these studies suggest that bacteria capable of producing volatile metabolites, including trimethylamine-N-oxide (TMAO) and but...
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| Veröffentlicht in: | Translational stroke research 2021-08, Vol.12 (4), p.581-592 |
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| creator | Haak, Bastiaan W. Westendorp, Willeke F. van Engelen, Tjitske S. R. Brands, Xanthe Brouwer, Matthijs C. Vermeij, Jan-Dirk Hugenholtz, Floor Verhoeven, Aswin Derks, Rico J. Giera, Martin Nederkoorn, Paul J. de Vos, Willem M. van de Beek, Diederik Wiersinga, W. Joost |
| description | In recent years, preclinical studies have illustrated the potential role of intestinal bacterial composition in the risk of stroke and post-stroke infections. The results of these studies suggest that bacteria capable of producing volatile metabolites, including trimethylamine-N-oxide (TMAO) and butyrate, play opposing, yet important roles in the cascade of events leading to stroke. However, no large-scale studies have been undertaken to determine the abundance of these bacterial communities in stroke patients and to assess the impact of disrupted compositions of the intestinal microbiota on patient outcomes. In this prospective case–control study, rectal swabs from 349 ischemic and hemorrhagic stroke patients (median age, 71 years; IQR: 67–75) were collected within 24 h of hospital admission. Samples were subjected to 16S rRNA amplicon sequencing and subsequently compared with samples obtained from 51 outpatient age- and sex-matched controls (median age, 72 years; IQR, 62–80) with similar cardiovascular risk profiles but without active signs of stroke. Plasma protein biomarkers were analyzed using a combination of nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography–mass spectrometry (LC-MS). Alpha and beta diversity analyses revealed higher disruption of intestinal communities during ischemic and hemorrhagic stroke compared with non-stroke matched control subjects. Additionally, we observed an enrichment of bacteria implicated in TMAO production and a loss of butyrate-producing bacteria. Stroke patients displayed two-fold lower plasma levels of TMAO than controls (median 1.97 vs 4.03 μM, Wilcoxon
p
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| doi_str_mv | 10.1007/s12975-020-00863-4 |
| format | Article |
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p
< 0.0001). Finally, lower abundance of butyrate-producing bacteria within 24 h of hospital admission was an independent predictor of enhanced risk of post-stroke infection (odds ratio 0.77,
p
= 0.005), but not of mortality or functional patient outcome. In conclusion, aberrations in trimethylamine- and butyrate-producing gut bacteria are associated with stroke and stroke-associated infections.</description><identifier>ISSN: 1868-4483</identifier><identifier>EISSN: 1868-601X</identifier><identifier>DOI: 10.1007/s12975-020-00863-4</identifier><identifier>PMID: 33052545</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Aged ; Anaerobiosis ; Antibiotics ; Bacteria ; Biomarkers ; Biomedical and Life Sciences ; Biomedicine ; Cardiology ; Case-Control Studies ; Diabetes ; Gastrointestinal Microbiome ; Hemorrhage ; Humans ; Infections ; Ischemia ; Metabolites ; Microbiota ; Neurology ; Neurosciences ; Neurosurgery ; NMR ; Nuclear magnetic resonance ; Original ; Original Article ; Pathogenesis ; Plasma ; Proteins ; RNA, Ribosomal, 16S - genetics ; Statistical analysis ; Stroke ; Vascular Surgery</subject><ispartof>Translational stroke research, 2021-08, Vol.12 (4), p.581-592</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-a24ee119f51d52d0526d5cee773cf56b9819a0969694f9fba17b0009e786d4a23</citedby><cites>FETCH-LOGICAL-c474t-a24ee119f51d52d0526d5cee773cf56b9819a0969694f9fba17b0009e786d4a23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12975-020-00863-4$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2919478104?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>230,314,776,780,881,21367,27901,27902,33721,33722,41464,42533,43781,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33052545$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Haak, Bastiaan W.</creatorcontrib><creatorcontrib>Westendorp, Willeke F.</creatorcontrib><creatorcontrib>van Engelen, Tjitske S. R.</creatorcontrib><creatorcontrib>Brands, Xanthe</creatorcontrib><creatorcontrib>Brouwer, Matthijs C.</creatorcontrib><creatorcontrib>Vermeij, Jan-Dirk</creatorcontrib><creatorcontrib>Hugenholtz, Floor</creatorcontrib><creatorcontrib>Verhoeven, Aswin</creatorcontrib><creatorcontrib>Derks, Rico J.</creatorcontrib><creatorcontrib>Giera, Martin</creatorcontrib><creatorcontrib>Nederkoorn, Paul J.</creatorcontrib><creatorcontrib>de Vos, Willem M.</creatorcontrib><creatorcontrib>van de Beek, Diederik</creatorcontrib><creatorcontrib>Wiersinga, W. Joost</creatorcontrib><title>Disruptions of Anaerobic Gut Bacteria Are Associated with Stroke and Post-stroke Infection: a Prospective Case–Control Study</title><title>Translational stroke research</title><addtitle>Transl. Stroke Res</addtitle><addtitle>Transl Stroke Res</addtitle><description>In recent years, preclinical studies have illustrated the potential role of intestinal bacterial composition in the risk of stroke and post-stroke infections. The results of these studies suggest that bacteria capable of producing volatile metabolites, including trimethylamine-N-oxide (TMAO) and butyrate, play opposing, yet important roles in the cascade of events leading to stroke. However, no large-scale studies have been undertaken to determine the abundance of these bacterial communities in stroke patients and to assess the impact of disrupted compositions of the intestinal microbiota on patient outcomes. In this prospective case–control study, rectal swabs from 349 ischemic and hemorrhagic stroke patients (median age, 71 years; IQR: 67–75) were collected within 24 h of hospital admission. Samples were subjected to 16S rRNA amplicon sequencing and subsequently compared with samples obtained from 51 outpatient age- and sex-matched controls (median age, 72 years; IQR, 62–80) with similar cardiovascular risk profiles but without active signs of stroke. Plasma protein biomarkers were analyzed using a combination of nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography–mass spectrometry (LC-MS). Alpha and beta diversity analyses revealed higher disruption of intestinal communities during ischemic and hemorrhagic stroke compared with non-stroke matched control subjects. Additionally, we observed an enrichment of bacteria implicated in TMAO production and a loss of butyrate-producing bacteria. Stroke patients displayed two-fold lower plasma levels of TMAO than controls (median 1.97 vs 4.03 μM, Wilcoxon
p
< 0.0001). Finally, lower abundance of butyrate-producing bacteria within 24 h of hospital admission was an independent predictor of enhanced risk of post-stroke infection (odds ratio 0.77,
p
= 0.005), but not of mortality or functional patient outcome. In conclusion, aberrations in trimethylamine- and butyrate-producing gut bacteria are associated with stroke and stroke-associated infections.</description><subject>Aged</subject><subject>Anaerobiosis</subject><subject>Antibiotics</subject><subject>Bacteria</subject><subject>Biomarkers</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cardiology</subject><subject>Case-Control Studies</subject><subject>Diabetes</subject><subject>Gastrointestinal Microbiome</subject><subject>Hemorrhage</subject><subject>Humans</subject><subject>Infections</subject><subject>Ischemia</subject><subject>Metabolites</subject><subject>Microbiota</subject><subject>Neurology</subject><subject>Neurosciences</subject><subject>Neurosurgery</subject><subject>NMR</subject><subject>Nuclear magnetic resonance</subject><subject>Original</subject><subject>Original Article</subject><subject>Pathogenesis</subject><subject>Plasma</subject><subject>Proteins</subject><subject>RNA, Ribosomal, 16S - genetics</subject><subject>Statistical analysis</subject><subject>Stroke</subject><subject>Vascular Surgery</subject><issn>1868-4483</issn><issn>1868-601X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kc9u1DAQxi0EolXpC3BAlrhwCfh_Yg5IyxbaSpVaCZC4WY4zaV2y8WI7rXpBvANvyJPUS5ZSOGAf7JF_83lmPoSeUvKSElK_SpTpWlaEkYqQRvFKPEC7tFFNpQj9_HB7F6LhO2g_pUtSFqdCCf4Y7XBOJJNC7qJvBz7FaZ19GBMOPV6MFmJovcOHU8ZvrcsQvcWLCHiRUnDeZujwtc8X-EOO4QtgO3b4LKRcpTk-HntwG73X2OKzGNJ6E14BXtoEP7__WIaxgENJn7qbJ-hRb4cE-9tzD316_-7j8qg6OT08Xi5OKidqkSvLBAClupe0k6wrxatOOoC65q6XqtUN1ZZoVbbodd9aWrelXw11ozphGd9Db2bd9dSuoHNQarCDWUe_svHGBOvN3y-jvzDn4co0jPIy0CLwYisQw9cJUjYrnxwMgx0hTMkwISnlslayoM__QS_DFMfSnmGaalE3lIhCsZlyZUQpQn9XDCVm47CZHTbFYfPLYbNJena_jbuU334WgM9AKk_jOcQ_f_9H9hastLNi</recordid><startdate>20210801</startdate><enddate>20210801</enddate><creator>Haak, Bastiaan W.</creator><creator>Westendorp, Willeke F.</creator><creator>van Engelen, Tjitske S. 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Joost</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>C6C</scope><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PSYQQ</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20210801</creationdate><title>Disruptions of Anaerobic Gut Bacteria Are Associated with Stroke and Post-stroke Infection: a Prospective Case–Control Study</title><author>Haak, Bastiaan W. ; Westendorp, Willeke F. ; van Engelen, Tjitske S. R. ; Brands, Xanthe ; Brouwer, Matthijs C. ; Vermeij, Jan-Dirk ; Hugenholtz, Floor ; Verhoeven, Aswin ; Derks, Rico J. ; Giera, Martin ; Nederkoorn, Paul J. ; de Vos, Willem M. ; van de Beek, Diederik ; Wiersinga, W. 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Joost</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest One Psychology</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Translational stroke research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Haak, Bastiaan W.</au><au>Westendorp, Willeke F.</au><au>van Engelen, Tjitske S. R.</au><au>Brands, Xanthe</au><au>Brouwer, Matthijs C.</au><au>Vermeij, Jan-Dirk</au><au>Hugenholtz, Floor</au><au>Verhoeven, Aswin</au><au>Derks, Rico J.</au><au>Giera, Martin</au><au>Nederkoorn, Paul J.</au><au>de Vos, Willem M.</au><au>van de Beek, Diederik</au><au>Wiersinga, W. Joost</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Disruptions of Anaerobic Gut Bacteria Are Associated with Stroke and Post-stroke Infection: a Prospective Case–Control Study</atitle><jtitle>Translational stroke research</jtitle><stitle>Transl. Stroke Res</stitle><addtitle>Transl Stroke Res</addtitle><date>2021-08-01</date><risdate>2021</risdate><volume>12</volume><issue>4</issue><spage>581</spage><epage>592</epage><pages>581-592</pages><issn>1868-4483</issn><eissn>1868-601X</eissn><abstract>In recent years, preclinical studies have illustrated the potential role of intestinal bacterial composition in the risk of stroke and post-stroke infections. The results of these studies suggest that bacteria capable of producing volatile metabolites, including trimethylamine-N-oxide (TMAO) and butyrate, play opposing, yet important roles in the cascade of events leading to stroke. However, no large-scale studies have been undertaken to determine the abundance of these bacterial communities in stroke patients and to assess the impact of disrupted compositions of the intestinal microbiota on patient outcomes. In this prospective case–control study, rectal swabs from 349 ischemic and hemorrhagic stroke patients (median age, 71 years; IQR: 67–75) were collected within 24 h of hospital admission. Samples were subjected to 16S rRNA amplicon sequencing and subsequently compared with samples obtained from 51 outpatient age- and sex-matched controls (median age, 72 years; IQR, 62–80) with similar cardiovascular risk profiles but without active signs of stroke. Plasma protein biomarkers were analyzed using a combination of nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography–mass spectrometry (LC-MS). Alpha and beta diversity analyses revealed higher disruption of intestinal communities during ischemic and hemorrhagic stroke compared with non-stroke matched control subjects. Additionally, we observed an enrichment of bacteria implicated in TMAO production and a loss of butyrate-producing bacteria. Stroke patients displayed two-fold lower plasma levels of TMAO than controls (median 1.97 vs 4.03 μM, Wilcoxon
p
< 0.0001). Finally, lower abundance of butyrate-producing bacteria within 24 h of hospital admission was an independent predictor of enhanced risk of post-stroke infection (odds ratio 0.77,
p
= 0.005), but not of mortality or functional patient outcome. In conclusion, aberrations in trimethylamine- and butyrate-producing gut bacteria are associated with stroke and stroke-associated infections.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>33052545</pmid><doi>10.1007/s12975-020-00863-4</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Aged Anaerobiosis Antibiotics Bacteria Biomarkers Biomedical and Life Sciences Biomedicine Cardiology Case-Control Studies Diabetes Gastrointestinal Microbiome Hemorrhage Humans Infections Ischemia Metabolites Microbiota Neurology Neurosciences Neurosurgery NMR Nuclear magnetic resonance Original Original Article Pathogenesis Plasma Proteins RNA, Ribosomal, 16S - genetics Statistical analysis Stroke Vascular Surgery |
| title | Disruptions of Anaerobic Gut Bacteria Are Associated with Stroke and Post-stroke Infection: a Prospective Case–Control Study |
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