Gastrointestinal pathogen colonization and the microbiome in asymptomatic kidney transplant recipients
Background In kidney transplant recipients, gastrointestinal (GI) pathogens in feces are only evaluated during diarrheal episodes. Little is known about the prevalence of GI pathogens in asymptomatic individuals in this population. Methods We recruited 142 kidney transplant recipients who provided a...
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          | Published in | Transplant infectious disease Vol. 21; no. 6; pp. e13167 - n/a | 
|---|---|
| Main Authors | , , , , , , , , , , , , , , | 
| Format | Journal Article | 
| Language | English | 
| Published | 
        Denmark
          Wiley Subscription Services, Inc
    
        01.12.2019
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| Subjects | |
| Online Access | Get full text | 
| ISSN | 1398-2273 1399-3062 1399-3062  | 
| DOI | 10.1111/tid.13167 | 
Cover
| Abstract | Background
In kidney transplant recipients, gastrointestinal (GI) pathogens in feces are only evaluated during diarrheal episodes. Little is known about the prevalence of GI pathogens in asymptomatic individuals in this population.
Methods
We recruited 142 kidney transplant recipients who provided a non‐diarrheal fecal sample within the first 10 days after transplantation. The specimens were evaluated for GI pathogens using the BioFire® FilmArray® GI Panel (BioFire Diagnostics, LLC), which tests for 22 pathogens. The fecal microbiome was also characterized using 16S rRNA gene sequencing of the V4‐V5 hypervariable region. We evaluated whether detection of Clostridioides difficile and other GI pathogens was associated with post‐transplant diarrhea within the first 3 months after transplantation.
Results
Among the 142 subjects, a potential pathogen was detected in 43 (30%) using the GI Panel. The most common organisms detected were C difficile (n = 24, 17%), enteropathogenic Escherichia coli (n = 8, 6%), and norovirus (n = 5, 4%). Detection of a pathogen on the GI panel or detection of C difficile alone was not associated with future post‐transplant diarrhea (P > .05). The estimated number of gut bacterial species was significantly lower in subjects colonized with C difficile than those not colonized with a GI pathogen (P = .01).
Conclusion
Colonization with GI pathogens, particularly C difficile, is common at the time of kidney transplantation but does not predict subsequent diarrhea. Detection of C difficile carriage was associated with decreased microbial diversity and may be a biomarker of gut dysbiosis. | 
    
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| AbstractList | Background
In kidney transplant recipients, gastrointestinal (GI) pathogens in feces are only evaluated during diarrheal episodes. Little is known about the prevalence of GI pathogens in asymptomatic individuals in this population.
Methods
We recruited 142 kidney transplant recipients who provided a non‐diarrheal fecal sample within the first 10 days after transplantation. The specimens were evaluated for GI pathogens using the BioFire® FilmArray® GI Panel (BioFire Diagnostics, LLC), which tests for 22 pathogens. The fecal microbiome was also characterized using 16S rRNA gene sequencing of the V4‐V5 hypervariable region. We evaluated whether detection of Clostridioides difficile and other GI pathogens was associated with post‐transplant diarrhea within the first 3 months after transplantation.
Results
Among the 142 subjects, a potential pathogen was detected in 43 (30%) using the GI Panel. The most common organisms detected were C difficile (n = 24, 17%), enteropathogenic Escherichia coli (n = 8, 6%), and norovirus (n = 5, 4%). Detection of a pathogen on the GI panel or detection of C difficile alone was not associated with future post‐transplant diarrhea (P > .05). The estimated number of gut bacterial species was significantly lower in subjects colonized with C difficile than those not colonized with a GI pathogen (P = .01).
Conclusion
Colonization with GI pathogens, particularly C difficile, is common at the time of kidney transplantation but does not predict subsequent diarrhea. Detection of C difficile carriage was associated with decreased microbial diversity and may be a biomarker of gut dysbiosis. In kidney transplant recipients, gastrointestinal (GI) pathogens in feces are only evaluated during diarrheal episodes. Little is known about the prevalence of GI pathogens in asymptomatic individuals in this population.BACKGROUNDIn kidney transplant recipients, gastrointestinal (GI) pathogens in feces are only evaluated during diarrheal episodes. Little is known about the prevalence of GI pathogens in asymptomatic individuals in this population.We recruited 142 kidney transplant recipients who provided a non-diarrheal fecal sample within the first 10 days after transplantation. The specimens were evaluated for GI pathogens using the BioFire® FilmArray® GI Panel (BioFire Diagnostics, LLC), which tests for 22 pathogens. The fecal microbiome was also characterized using 16S rRNA gene sequencing of the V4-V5 hypervariable region. We evaluated whether detection of Clostridioides difficile and other GI pathogens was associated with post-transplant diarrhea within the first 3 months after transplantation.METHODSWe recruited 142 kidney transplant recipients who provided a non-diarrheal fecal sample within the first 10 days after transplantation. The specimens were evaluated for GI pathogens using the BioFire® FilmArray® GI Panel (BioFire Diagnostics, LLC), which tests for 22 pathogens. The fecal microbiome was also characterized using 16S rRNA gene sequencing of the V4-V5 hypervariable region. We evaluated whether detection of Clostridioides difficile and other GI pathogens was associated with post-transplant diarrhea within the first 3 months after transplantation.Among the 142 subjects, a potential pathogen was detected in 43 (30%) using the GI Panel. The most common organisms detected were C difficile (n = 24, 17%), enteropathogenic Escherichia coli (n = 8, 6%), and norovirus (n = 5, 4%). Detection of a pathogen on the GI panel or detection of C difficile alone was not associated with future post-transplant diarrhea (P > .05). The estimated number of gut bacterial species was significantly lower in subjects colonized with C difficile than those not colonized with a GI pathogen (P = .01).RESULTSAmong the 142 subjects, a potential pathogen was detected in 43 (30%) using the GI Panel. The most common organisms detected were C difficile (n = 24, 17%), enteropathogenic Escherichia coli (n = 8, 6%), and norovirus (n = 5, 4%). Detection of a pathogen on the GI panel or detection of C difficile alone was not associated with future post-transplant diarrhea (P > .05). The estimated number of gut bacterial species was significantly lower in subjects colonized with C difficile than those not colonized with a GI pathogen (P = .01).Colonization with GI pathogens, particularly C difficile, is common at the time of kidney transplantation but does not predict subsequent diarrhea. Detection of C difficile carriage was associated with decreased microbial diversity and may be a biomarker of gut dysbiosis.CONCLUSIONColonization with GI pathogens, particularly C difficile, is common at the time of kidney transplantation but does not predict subsequent diarrhea. Detection of C difficile carriage was associated with decreased microbial diversity and may be a biomarker of gut dysbiosis. In kidney transplant recipients, gastrointestinal (GI) pathogens in feces are only evaluated during diarrheal episodes. Little is known about the prevalence of GI pathogens in asymptomatic individuals in this population. We recruited 142 kidney transplant recipients who provided a non-diarrheal fecal sample within the first 10 days after transplantation. The specimens were evaluated for GI pathogens using the BioFire FilmArray GI Panel (BioFire Diagnostics, LLC), which tests for 22 pathogens. The fecal microbiome was also characterized using 16S rRNA gene sequencing of the V4-V5 hypervariable region. We evaluated whether detection of Clostridioides difficile and other GI pathogens was associated with post-transplant diarrhea within the first 3 months after transplantation. Among the 142 subjects, a potential pathogen was detected in 43 (30%) using the GI Panel. The most common organisms detected were C difficile (n = 24, 17%), enteropathogenic Escherichia coli (n = 8, 6%), and norovirus (n = 5, 4%). Detection of a pathogen on the GI panel or detection of C difficile alone was not associated with future post-transplant diarrhea (P > .05). The estimated number of gut bacterial species was significantly lower in subjects colonized with C difficile than those not colonized with a GI pathogen (P = .01). Colonization with GI pathogens, particularly C difficile, is common at the time of kidney transplantation but does not predict subsequent diarrhea. Detection of C difficile carriage was associated with decreased microbial diversity and may be a biomarker of gut dysbiosis. BackgroundIn kidney transplant recipients, gastrointestinal (GI) pathogens in feces are only evaluated during diarrheal episodes. Little is known about the prevalence of GI pathogens in asymptomatic individuals in this population.MethodsWe recruited 142 kidney transplant recipients who provided a non‐diarrheal fecal sample within the first 10 days after transplantation. The specimens were evaluated for GI pathogens using the BioFire® FilmArray® GI Panel (BioFire Diagnostics, LLC), which tests for 22 pathogens. The fecal microbiome was also characterized using 16S rRNA gene sequencing of the V4‐V5 hypervariable region. We evaluated whether detection of Clostridioides difficile and other GI pathogens was associated with post‐transplant diarrhea within the first 3 months after transplantation.ResultsAmong the 142 subjects, a potential pathogen was detected in 43 (30%) using the GI Panel. The most common organisms detected were C difficile (n = 24, 17%), enteropathogenic Escherichia coli (n = 8, 6%), and norovirus (n = 5, 4%). Detection of a pathogen on the GI panel or detection of C difficile alone was not associated with future post‐transplant diarrhea (P > .05). The estimated number of gut bacterial species was significantly lower in subjects colonized with C difficile than those not colonized with a GI pathogen (P = .01).ConclusionColonization with GI pathogens, particularly C difficile, is common at the time of kidney transplantation but does not predict subsequent diarrhea. Detection of C difficile carriage was associated with decreased microbial diversity and may be a biomarker of gut dysbiosis.  | 
    
| Author | Alston, Tricia Lubetzky, Michelle Chan, Kevin Zhang, Lisa T. Albakry, Shady Edusei, Emmanuel Lee, John R. Westblade, Lars F. Robertson, Amy Magruder, Matthew Dadhania, Darshana M. Suthanthiran, Manikkam Pamer, Eric G. Botticelli, Brittany Satlin, Michael J.  | 
    
| AuthorAffiliation | 1 Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA 5 Department of Transplantation Medicine, NewYork-Presbyterian Hospital – Weill Cornell Medical Center, New York, NY, USA 2 Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, NY, USA 4 NewYork-Presbyterian Hospital – Weill Cornell Medical Center, New York, NY, USA 6 Infectious Disease Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA 3 Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medicine, New York, NY, USA  | 
    
| AuthorAffiliation_xml | – name: 5 Department of Transplantation Medicine, NewYork-Presbyterian Hospital – Weill Cornell Medical Center, New York, NY, USA – name: 3 Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medicine, New York, NY, USA – name: 1 Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA – name: 2 Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, NY, USA – name: 6 Infectious Disease Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA – name: 4 NewYork-Presbyterian Hospital – Weill Cornell Medical Center, New York, NY, USA  | 
    
| Author_xml | – sequence: 1 givenname: Lars F. surname: Westblade fullname: Westblade, Lars F. email: law9067@med.cornell.edu organization: Weill Cornell Medicine – sequence: 2 givenname: Michael J. orcidid: 0000-0003-4711-5334 surname: Satlin fullname: Satlin, Michael J. organization: Weill Cornell Medicine – sequence: 3 givenname: Shady surname: Albakry fullname: Albakry, Shady organization: NewYork Presbyterian Hospital ‐ Weill Cornell Medical Center – sequence: 4 givenname: Brittany surname: Botticelli fullname: Botticelli, Brittany organization: NewYork Presbyterian Hospital ‐ Weill Cornell Medical Center – sequence: 5 givenname: Amy surname: Robertson fullname: Robertson, Amy organization: NewYork Presbyterian Hospital ‐ Weill Cornell Medical Center – sequence: 6 givenname: Tricia surname: Alston fullname: Alston, Tricia organization: NewYork Presbyterian Hospital ‐ Weill Cornell Medical Center – sequence: 7 givenname: Matthew surname: Magruder fullname: Magruder, Matthew organization: NewYork Presbyterian Hospital ‐ Weill Cornell Medical Center – sequence: 8 givenname: Lisa T. surname: Zhang fullname: Zhang, Lisa T. organization: NewYork Presbyterian Hospital ‐ Weill Cornell Medical Center – sequence: 9 givenname: Emmanuel surname: Edusei fullname: Edusei, Emmanuel organization: NewYork Presbyterian Hospital ‐ Weill Cornell Medical Center – sequence: 10 givenname: Kevin surname: Chan fullname: Chan, Kevin organization: NewYork Presbyterian Hospital ‐ Weill Cornell Medical Center – sequence: 11 givenname: Michelle surname: Lubetzky fullname: Lubetzky, Michelle organization: NewYork‐Presbyterian Hospital – sequence: 12 givenname: Darshana M. surname: Dadhania fullname: Dadhania, Darshana M. organization: NewYork‐Presbyterian Hospital – sequence: 13 givenname: Eric G. surname: Pamer fullname: Pamer, Eric G. organization: Memorial Sloan Kettering Cancer Center – sequence: 14 givenname: Manikkam surname: Suthanthiran fullname: Suthanthiran, Manikkam organization: NewYork‐Presbyterian Hospital – sequence: 15 givenname: John R. orcidid: 0000-0002-9612-5742 surname: Lee fullname: Lee, John R. email: jrl2002@med.cornell.edu organization: NewYork‐Presbyterian Hospital  | 
    
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| Keywords | Clostridioides difficile gastrointestinal panel colonization diarrhea microbiome kidney transplantation  | 
    
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| Notes | Funding information This research work was supported, in part, by an investigator‐initiated research grant from BioFire Diagnostics, LLC; and by K23 AI 124464 from the National Institute of Allergy and Infectious Diseases to JRL and R37 AI 051652 from the National Institute of Allergy and Infectious Diseases to MS ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 L.F.W., M.J.S., E.G.P., M.S., and J.R.L. participated in the study design, analysis, and writing of the manuscript S.A., B.B., A.R., T.A., M.M., L.T.Z., E.E., and K.C. participated in the processing of specimens and data analysis Authorship M.L. and D.M.D. participated in the analysis and writing of the manuscript  | 
    
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| References_xml | – volume: 20 issue: 4 year: 2018 article-title: Risk factors associated with Clostridium difficile infection in kidney transplant recipients publication-title: Transpl Infect Dis – volume: 53 start-page: 915 issue: 3 year: 2015 end-page: 925 article-title: Multicenter evaluation of the BioFire FilmArray gastrointestinal panel for etiologic diagnosis of infectious gastroenteritis publication-title: J Clin Microbiol – volume: 10 start-page: 996 issue: 10 year: 2013 end-page: 998 article-title: UPARSE: highly accurate OTU sequences from microbial amplicon reads publication-title: Nat Methods – volume: 6 start-page: 1621 issue: 8 year: 2012 end-page: 1624 article-title: Ultra‐high‐throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms publication-title: ISME J – volume: 10 issue: 4 year: 2015 article-title: Prevalence of Clostridium difficile infection among solid organ transplant recipients: a meta‐analysis of published studies publication-title: PLoS ONE – year: 2005 – volume: 19 start-page: 488 issue: 2 year: 2019 end-page: 500 article-title: Gut microbiota dysbiosis and diarrhea in kidney transplant recipients publication-title: Am J Transplant – volume: 9 start-page: 270 issue: 4 year: 2007 end-page: 275 article-title: Etiologic agents of diarrhea in solid organ recipients publication-title: Transpl Infect Dis – volume: 60 start-page: 729 issue: 5 year: 2015 end-page: 737 article-title: Diagnostic yields in solid organ transplant recipients admitted with diarrhea publication-title: Clin Infect Dis – volume: 31 start-page: 3476 issue: 21 year: 2015 end-page: 3482 article-title: Error filtering, pair assembly and error correction for next‐generation sequencing reads publication-title: Bioinformatics – volume: 68 start-page: 391 issue: 3 year: 1999 end-page: 396 article-title: Mycophenolate mofetil in renal transplantation: 3‐year results from the placebo‐controlled trial. European Mycophenolate Mofetil Cooperative Study Group publication-title: Transplantation – volume: 98 start-page: 697 issue: 7 year: 2014 end-page: 705 article-title: Gut microbial community structure and complications after kidney transplantation: a pilot study publication-title: Transplantation – volume: 42 start-page: D553 issue: D1 year: 2014 end-page: D559 article-title: RefSeq microbial genomes database: new representation and annotation strategy publication-title: Nucleic Acids Res – volume: 215 start-page: 403 issue: 3 year: 1990 end-page: 410 article-title: Basic local alignment search tool publication-title: J Mol Biol – volume: 369 start-page: 1195 issue: 13 year: 2013 end-page: 1205 article-title: Diverse sources of C. difficile infection identified on whole‐genome sequencing publication-title: N Engl J Med – volume: 175 start-page: 1792 issue: 11 year: 2015 end-page: 1801 article-title: Overdiagnosis of Clostridium difficile Infection in the Molecular Test Era publication-title: JAMA Intern Med – volume: 26 start-page: 231 issue: 3 year: 2016 end-page: 237 article-title: Risk Factors for Clostridium Difficile Diarrhea in Patients With Solid Organ Transplantation publication-title: Prog Transplant – ident: e_1_2_9_15_1 doi: 10.1016/S0022-2836(05)80360-2 – ident: e_1_2_9_4_1 doi: 10.1093/cid/ciu880 – ident: e_1_2_9_9_1 doi: 10.1128/JCM.02674-14 – ident: e_1_2_9_10_1 – ident: e_1_2_9_2_1 doi: 10.1097/00007890-199908150-00011 – ident: e_1_2_9_13_1 doi: 10.1038/nmeth.2604 – ident: e_1_2_9_14_1 doi: 10.1093/bioinformatics/btv401 – ident: e_1_2_9_8_1 doi: 10.1111/ajt.14974 – ident: e_1_2_9_6_1 doi: 10.1177/1526924816655073 – ident: e_1_2_9_16_1 doi: 10.1093/nar/gkt1274 – ident: e_1_2_9_5_1 doi: 10.1371/journal.pone.0124483 – ident: e_1_2_9_17_1 doi: 10.1001/jamainternmed.2015.4114 – ident: e_1_2_9_18_1 doi: 10.1056/NEJMoa1216064 – ident: e_1_2_9_12_1 doi: 10.1038/ismej.2012.8 – ident: e_1_2_9_3_1 doi: 10.1111/j.1399-3062.2007.00237.x – ident: e_1_2_9_7_1 doi: 10.1111/tid.12918 – ident: e_1_2_9_11_1 doi: 10.1097/TP.0000000000000370  | 
    
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In kidney transplant recipients, gastrointestinal (GI) pathogens in feces are only evaluated during diarrheal episodes. Little is known about the... In kidney transplant recipients, gastrointestinal (GI) pathogens in feces are only evaluated during diarrheal episodes. Little is known about the prevalence of... BackgroundIn kidney transplant recipients, gastrointestinal (GI) pathogens in feces are only evaluated during diarrheal episodes. Little is known about the...  | 
    
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| SubjectTerms | Adult Aged Asymptomatic Infections - epidemiology Biomarkers Clostridioides difficile Clostridium difficile - genetics Clostridium difficile - isolation & purification Colonization Diarrhea Digestive system DNA, Bacterial - isolation & purification Dysbacteriosis Dysbiosis - diagnosis Dysbiosis - epidemiology Dysbiosis - microbiology E coli Enteropathogenic Escherichia coli - genetics Enteropathogenic Escherichia coli - isolation & purification Fecal microflora Feces - microbiology Female Gastrointestinal Microbiome - genetics gastrointestinal panel Gastrointestinal tract Gene sequencing Humans Intestinal Mucosa - immunology Intestinal Mucosa - microbiology Kidney transplantation Kidney Transplantation - adverse effects Kidney transplants Male microbiome Microbiomes Microorganisms Middle Aged Norovirus Norovirus - genetics Norovirus - isolation & purification Pathogens Retrospective Studies RNA, Ribosomal, 16S - genetics RNA, Viral - isolation & purification rRNA 16S Transplants & implants  | 
    
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| Title | Gastrointestinal pathogen colonization and the microbiome in asymptomatic kidney transplant recipients | 
    
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