Gut microbiota and tacrolimus dosing in kidney transplantation
Tacrolimus dosing to establish therapeutic levels in recipients of organ transplants is a challenging task because of much interpatient and intrapatient variability in drug absorption, metabolism, and disposition. In view of the reported impact of gut microbial species on drug metabolism, we investi...
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| description | Tacrolimus dosing to establish therapeutic levels in recipients of organ transplants is a challenging task because of much interpatient and intrapatient variability in drug absorption, metabolism, and disposition. In view of the reported impact of gut microbial species on drug metabolism, we investigated the relationship between the gut microbiota and tacrolimus dosing requirements in this pilot study of adult kidney transplant recipients. Serial fecal specimens were collected during the first month of transplantation from 19 kidney transplant recipients who either required a 50% increase from initial tacrolimus dosing during the first month of transplantation (Dose Escalation Group, n=5) or did not require such an increase (Dose Stable Group, n=14). We characterized bacterial composition in the fecal specimens by deep sequencing of the PCR amplified 16S rRNA V4-V5 region and we investigated the hypothesis that gut microbial composition is associated with tacrolimus dosing requirements. Initial tacrolimus dosing was similar in the Dose Escalation Group and in the Stable Group (4.2 ± 1.1 mg/day vs. 3.8 ± 0.8 mg/day, respectively, P=0.61, two-way between-group ANOVA using contrasts) but became higher in the Dose Escalation Group than in the Dose Stable Group by the end of the first transplantation month (9.6 ± 2.4 mg/day vs. 3.3 ± 1.5 mg/day, respectively, P |
| doi_str_mv | 10.1371/journal.pone.0122399 |
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In view of the reported impact of gut microbial species on drug metabolism, we investigated the relationship between the gut microbiota and tacrolimus dosing requirements in this pilot study of adult kidney transplant recipients. Serial fecal specimens were collected during the first month of transplantation from 19 kidney transplant recipients who either required a 50% increase from initial tacrolimus dosing during the first month of transplantation (Dose Escalation Group, n=5) or did not require such an increase (Dose Stable Group, n=14). We characterized bacterial composition in the fecal specimens by deep sequencing of the PCR amplified 16S rRNA V4-V5 region and we investigated the hypothesis that gut microbial composition is associated with tacrolimus dosing requirements. Initial tacrolimus dosing was similar in the Dose Escalation Group and in the Stable Group (4.2 ± 1.1 mg/day vs. 3.8 ± 0.8 mg/day, respectively, P=0.61, two-way between-group ANOVA using contrasts) but became higher in the Dose Escalation Group than in the Dose Stable Group by the end of the first transplantation month (9.6 ± 2.4 mg/day vs. 3.3 ± 1.5 mg/day, respectively, P<0.001). Our systematic characterization of the gut microbial composition identified that fecal Faecalibacterium prausnitzii abundance in the first week of transplantation was 11.8% in the Dose Escalation Group and 0.8% in the Dose Stable Group (P=0.002, Wilcoxon Rank Sum test, P<0.05 after Benjamini-Hochberg correction for multiple hypotheses). Fecal Faecalibacterium prausnitzii abundance in the first week of transplantation was positively correlated with future tacrolimus dosing at 1 month (R=0.57, P=0.01) and had a coefficient ± standard error of 1.0 ± 0.6 (P=0.08) after multivariable linear regression. Our novel observations may help further explain inter-individual differences in tacrolimus dosing to achieve therapeutic levels.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0122399</identifier><identifier>PMID: 25815766</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Abundance ; Adult ; Aged ; Antibiotics ; Bacteria - drug effects ; Bioinformatics ; Cancer ; Composition ; Dosage ; Dose-Response Relationship, Drug ; Drug dosages ; Drug metabolism ; Enterococcus ; Faecalibacterium prausnitzii ; Feces ; Feces - microbiology ; Female ; Gastrointestinal Microbiome - genetics ; Graft Rejection - drug therapy ; Graft Rejection - genetics ; Graft Rejection - microbiology ; Health aspects ; Hospitals ; Humans ; Hypertension ; Infectious diseases ; Inflammation ; Intestinal microflora ; Kidney Transplantation ; Kidney transplants ; Kidneys ; Male ; Medicine ; Metabolism ; Microbiota ; Microbiota (Symbiotic organisms) ; Microorganisms ; Middle Aged ; Nephrology ; Organ transplant recipients ; Physiological aspects ; RNA ; RNA, Ribosomal, 16S - genetics ; rRNA 16S ; Standard error ; Systematic review ; Tacrolimus ; Tacrolimus - administration & dosage ; Transplant Recipients ; Transplantation ; Transplants ; Transplants & implants ; Variance analysis</subject><ispartof>PloS one, 2015-03, Vol.10 (3), p.e0122399-e0122399</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Lee et al 2015 Lee et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-fe0b29faaaff97dc062ef232898e61999e3cd2ae33f8a5aafd6258d3a3fb7d123</citedby><cites>FETCH-LOGICAL-c758t-fe0b29faaaff97dc062ef232898e61999e3cd2ae33f8a5aafd6258d3a3fb7d123</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4376942/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4376942/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25815766$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, John R</creatorcontrib><creatorcontrib>Muthukumar, Thangamani</creatorcontrib><creatorcontrib>Dadhania, Darshana</creatorcontrib><creatorcontrib>Taur, Ying</creatorcontrib><creatorcontrib>Jenq, Robert R</creatorcontrib><creatorcontrib>Toussaint, Nora C</creatorcontrib><creatorcontrib>Ling, Lilan</creatorcontrib><creatorcontrib>Pamer, Eric</creatorcontrib><creatorcontrib>Suthanthiran, Manikkam</creatorcontrib><title>Gut microbiota and tacrolimus dosing in kidney transplantation</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Tacrolimus dosing to establish therapeutic levels in recipients of organ transplants is a challenging task because of much interpatient and intrapatient variability in drug absorption, metabolism, and disposition. 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Our novel observations may help further explain inter-individual differences in tacrolimus dosing to achieve therapeutic levels.</description><subject>Abundance</subject><subject>Adult</subject><subject>Aged</subject><subject>Antibiotics</subject><subject>Bacteria - drug effects</subject><subject>Bioinformatics</subject><subject>Cancer</subject><subject>Composition</subject><subject>Dosage</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug dosages</subject><subject>Drug metabolism</subject><subject>Enterococcus</subject><subject>Faecalibacterium prausnitzii</subject><subject>Feces</subject><subject>Feces - microbiology</subject><subject>Female</subject><subject>Gastrointestinal Microbiome - genetics</subject><subject>Graft Rejection - drug therapy</subject><subject>Graft Rejection - genetics</subject><subject>Graft Rejection - microbiology</subject><subject>Health aspects</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Infectious diseases</subject><subject>Inflammation</subject><subject>Intestinal microflora</subject><subject>Kidney Transplantation</subject><subject>Kidney transplants</subject><subject>Kidneys</subject><subject>Male</subject><subject>Medicine</subject><subject>Metabolism</subject><subject>Microbiota</subject><subject>Microbiota (Symbiotic organisms)</subject><subject>Microorganisms</subject><subject>Middle Aged</subject><subject>Nephrology</subject><subject>Organ transplant recipients</subject><subject>Physiological aspects</subject><subject>RNA</subject><subject>RNA, Ribosomal, 16S - genetics</subject><subject>rRNA 16S</subject><subject>Standard error</subject><subject>Systematic review</subject><subject>Tacrolimus</subject><subject>Tacrolimus - administration & dosage</subject><subject>Transplant Recipients</subject><subject>Transplantation</subject><subject>Transplants</subject><subject>Transplants & implants</subject><subject>Variance analysis</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl1v0zAUhiMEYqPwDxBEQkJw0RLbsRPfTJomGJUmTeLr1jqNj1uX1O5iB7F_j0OzqUG7QLlI7DznPV9vlr0kxYKwinzY-r5z0C723uGiIJQyKR9lp0QyOhe0YI-Pvk-yZyFsi4KzWoin2QnlNeGVEKfZ2WUf851tOr-yPkIOTucR0rG1uz7k2gfr1rl1-U-rHd7msQMX9i24CNF69zx7YqAN-GJ8z7Lvnz5-u_g8v7q-XF6cX82bitdxbrBYUWkAwBhZ6aYQFA1ltJY1CiKlRNZoCsiYqYEnSotUombAzKrShLJZ9vqgu299UGPrQREhKsKlFCIRywOhPWzVvrM76G6VB6v-XvhuraCLtmlRFVxXNdccTalLhhVwVjLJayMaibxmSetszNavdqgbdKntdiI6_ePsRq39L1WySshyKPfdKND5mx5DVDsbGmzT3ND3h7ql4Cwlm2Vv_kEf7m6k1pAasM74lLcZRNV5SUmdViuKRC0eoNKjMa04-cTYdD8JeD8JSEzE33ENfQhq-fXL_7PXP6bs2yN2g9DGTfBtP1gmTMHyACbHhdChuR8yKdRg87tpqMHmarR5Cnt1vKD7oDtfsz_4y_e2</recordid><startdate>20150327</startdate><enddate>20150327</enddate><creator>Lee, John R</creator><creator>Muthukumar, Thangamani</creator><creator>Dadhania, Darshana</creator><creator>Taur, Ying</creator><creator>Jenq, Robert R</creator><creator>Toussaint, Nora C</creator><creator>Ling, Lilan</creator><creator>Pamer, Eric</creator><creator>Suthanthiran, Manikkam</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150327</creationdate><title>Gut microbiota and tacrolimus dosing in kidney transplantation</title><author>Lee, John R ; Muthukumar, Thangamani ; Dadhania, Darshana ; Taur, Ying ; Jenq, Robert R ; Toussaint, Nora C ; Ling, Lilan ; Pamer, Eric ; Suthanthiran, Manikkam</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-fe0b29faaaff97dc062ef232898e61999e3cd2ae33f8a5aafd6258d3a3fb7d123</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Abundance</topic><topic>Adult</topic><topic>Aged</topic><topic>Antibiotics</topic><topic>Bacteria - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, John R</au><au>Muthukumar, Thangamani</au><au>Dadhania, Darshana</au><au>Taur, Ying</au><au>Jenq, Robert R</au><au>Toussaint, Nora C</au><au>Ling, Lilan</au><au>Pamer, Eric</au><au>Suthanthiran, Manikkam</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Gut microbiota and tacrolimus dosing in kidney transplantation</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-03-27</date><risdate>2015</risdate><volume>10</volume><issue>3</issue><spage>e0122399</spage><epage>e0122399</epage><pages>e0122399-e0122399</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Tacrolimus dosing to establish therapeutic levels in recipients of organ transplants is a challenging task because of much interpatient and intrapatient variability in drug absorption, metabolism, and disposition. In view of the reported impact of gut microbial species on drug metabolism, we investigated the relationship between the gut microbiota and tacrolimus dosing requirements in this pilot study of adult kidney transplant recipients. Serial fecal specimens were collected during the first month of transplantation from 19 kidney transplant recipients who either required a 50% increase from initial tacrolimus dosing during the first month of transplantation (Dose Escalation Group, n=5) or did not require such an increase (Dose Stable Group, n=14). We characterized bacterial composition in the fecal specimens by deep sequencing of the PCR amplified 16S rRNA V4-V5 region and we investigated the hypothesis that gut microbial composition is associated with tacrolimus dosing requirements. Initial tacrolimus dosing was similar in the Dose Escalation Group and in the Stable Group (4.2 ± 1.1 mg/day vs. 3.8 ± 0.8 mg/day, respectively, P=0.61, two-way between-group ANOVA using contrasts) but became higher in the Dose Escalation Group than in the Dose Stable Group by the end of the first transplantation month (9.6 ± 2.4 mg/day vs. 3.3 ± 1.5 mg/day, respectively, P<0.001). Our systematic characterization of the gut microbial composition identified that fecal Faecalibacterium prausnitzii abundance in the first week of transplantation was 11.8% in the Dose Escalation Group and 0.8% in the Dose Stable Group (P=0.002, Wilcoxon Rank Sum test, P<0.05 after Benjamini-Hochberg correction for multiple hypotheses). Fecal Faecalibacterium prausnitzii abundance in the first week of transplantation was positively correlated with future tacrolimus dosing at 1 month (R=0.57, P=0.01) and had a coefficient ± standard error of 1.0 ± 0.6 (P=0.08) after multivariable linear regression. Our novel observations may help further explain inter-individual differences in tacrolimus dosing to achieve therapeutic levels.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25815766</pmid><doi>10.1371/journal.pone.0122399</doi><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1667159966 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Abundance Adult Aged Antibiotics Bacteria - drug effects Bioinformatics Cancer Composition Dosage Dose-Response Relationship, Drug Drug dosages Drug metabolism Enterococcus Faecalibacterium prausnitzii Feces Feces - microbiology Female Gastrointestinal Microbiome - genetics Graft Rejection - drug therapy Graft Rejection - genetics Graft Rejection - microbiology Health aspects Hospitals Humans Hypertension Infectious diseases Inflammation Intestinal microflora Kidney Transplantation Kidney transplants Kidneys Male Medicine Metabolism Microbiota Microbiota (Symbiotic organisms) Microorganisms Middle Aged Nephrology Organ transplant recipients Physiological aspects RNA RNA, Ribosomal, 16S - genetics rRNA 16S Standard error Systematic review Tacrolimus Tacrolimus - administration & dosage Transplant Recipients Transplantation Transplants Transplants & implants Variance analysis |
| title | Gut microbiota and tacrolimus dosing in kidney transplantation |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-05T09%3A58%3A33IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Gut%20microbiota%20and%20tacrolimus%20dosing%20in%20kidney%20transplantation&rft.jtitle=PloS%20one&rft.au=Lee,%20John%20R&rft.date=2015-03-27&rft.volume=10&rft.issue=3&rft.spage=e0122399&rft.epage=e0122399&rft.pages=e0122399-e0122399&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0122399&rft_dat=%3Cgale_plos_%3EA421800560%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1667159966&rft_id=info:pmid/25815766&rft_galeid=A421800560&rft_doaj_id=oai_doaj_org_article_05d785d5ef4d43e7a5343958f6c9e583&rfr_iscdi=true |