Incongruence between dominant commensal donor microbes in recipient feces post fecal transplant and response to anti-PD-1 immunotherapy

Abstract Background To understand inter-individual variability of fecal microbe transplantation (FMT) to enhance anti-PD-1 immunotherapy (IT) for melanoma, we analyzed the data sets from two recent publications with a microbial strain-tracking tool to determine if donor strains were dominant in the...

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Main Authors: Hyunmin Koo, Casey D. Morrow
Format: Article
Language:English
Published: BMC 2021-09-01
Series:BMC Microbiology
Subjects:
Online Access:https://doi.org/10.1186/s12866-021-02312-0
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spelling doaj-4b97f9e5510d46e481152800e2d82d942021-09-26T11:08:59ZengBMCBMC Microbiology1471-21802021-09-0121111110.1186/s12866-021-02312-0Incongruence between dominant commensal donor microbes in recipient feces post fecal transplant and response to anti-PD-1 immunotherapyHyunmin Koo0Casey D. Morrow1Department of Genetics Hugh Kaul Personalized Medicine Institute, University of Alabama at BirminghamDepartment of Cell, Developmental and Integrative Biology Hugh Kaul Personalized Medicine Institute, University of Alabama at BirminghamAbstract Background To understand inter-individual variability of fecal microbe transplantation (FMT) to enhance anti-PD-1 immunotherapy (IT) for melanoma, we analyzed the data sets from two recent publications with a microbial strain-tracking tool to determine if donor strains were dominant in the recipient feces following FMT. Results Analysis of the Baruch et al. data set found that the presence of commensal donor microbes in recipient feces post-FMT did not correlate with the patient response to IT. From the Davar et al., data set, we found 4 patients that responded to IT had donor’s related strain post-FMT, while 2 patients that did not respond to the IT also had donor’s strain post-FMT. Importantly, we identified no donor microbes in the feces in one recipient post-FMT that responded to IT. Furthermore, in depth analysis from two patients who responded to IT revealed both donor and recipient strains at different times post-FMT. Colonization of the gastrointestinal tract niches is important for the interaction with the host immune system. Using a separate data set, we show that mucosa from the cecum, transverse colon, and sigmoid colon share strains, providing a large reservoir of niches containing recipient microbes. Conclusions We demonstrated using strain-tracking analysis individual variation with the respect to the presence of fecal dominant donor microbes in the recipient following FMT that did not correlate with the response to anti-PD-1 immunotherapy. The inter-individual differences of FMT to enhance IT might be explained by the variability of the donor microbes to occupy and outcompete recipient microbes for the gastrointestinal niches. The result from our study supports the use of new approaches to clear the niches in the gastrointestinal tract to promote donor colonization to reduce inter-individual variability of IT for melanoma and potentially other cancers.https://doi.org/10.1186/s12866-021-02312-0Fecal microbe transplantationAnti-PD-1 immunotherapyMetagenomicsStrain trackingGI tract colonization
collection DOAJ
language English
format Article
sources DOAJ
author Hyunmin Koo
Casey D. Morrow
spellingShingle Hyunmin Koo
Casey D. Morrow
Incongruence between dominant commensal donor microbes in recipient feces post fecal transplant and response to anti-PD-1 immunotherapy
BMC Microbiology
Fecal microbe transplantation
Anti-PD-1 immunotherapy
Metagenomics
Strain tracking
GI tract colonization
author_facet Hyunmin Koo
Casey D. Morrow
author_sort Hyunmin Koo
title Incongruence between dominant commensal donor microbes in recipient feces post fecal transplant and response to anti-PD-1 immunotherapy
title_short Incongruence between dominant commensal donor microbes in recipient feces post fecal transplant and response to anti-PD-1 immunotherapy
title_full Incongruence between dominant commensal donor microbes in recipient feces post fecal transplant and response to anti-PD-1 immunotherapy
title_fullStr Incongruence between dominant commensal donor microbes in recipient feces post fecal transplant and response to anti-PD-1 immunotherapy
title_full_unstemmed Incongruence between dominant commensal donor microbes in recipient feces post fecal transplant and response to anti-PD-1 immunotherapy
title_sort incongruence between dominant commensal donor microbes in recipient feces post fecal transplant and response to anti-pd-1 immunotherapy
publisher BMC
series BMC Microbiology
issn 1471-2180
publishDate 2021-09-01
description Abstract Background To understand inter-individual variability of fecal microbe transplantation (FMT) to enhance anti-PD-1 immunotherapy (IT) for melanoma, we analyzed the data sets from two recent publications with a microbial strain-tracking tool to determine if donor strains were dominant in the recipient feces following FMT. Results Analysis of the Baruch et al. data set found that the presence of commensal donor microbes in recipient feces post-FMT did not correlate with the patient response to IT. From the Davar et al., data set, we found 4 patients that responded to IT had donor’s related strain post-FMT, while 2 patients that did not respond to the IT also had donor’s strain post-FMT. Importantly, we identified no donor microbes in the feces in one recipient post-FMT that responded to IT. Furthermore, in depth analysis from two patients who responded to IT revealed both donor and recipient strains at different times post-FMT. Colonization of the gastrointestinal tract niches is important for the interaction with the host immune system. Using a separate data set, we show that mucosa from the cecum, transverse colon, and sigmoid colon share strains, providing a large reservoir of niches containing recipient microbes. Conclusions We demonstrated using strain-tracking analysis individual variation with the respect to the presence of fecal dominant donor microbes in the recipient following FMT that did not correlate with the response to anti-PD-1 immunotherapy. The inter-individual differences of FMT to enhance IT might be explained by the variability of the donor microbes to occupy and outcompete recipient microbes for the gastrointestinal niches. The result from our study supports the use of new approaches to clear the niches in the gastrointestinal tract to promote donor colonization to reduce inter-individual variability of IT for melanoma and potentially other cancers.
topic Fecal microbe transplantation
Anti-PD-1 immunotherapy
Metagenomics
Strain tracking
GI tract colonization
url https://doi.org/10.1186/s12866-021-02312-0
work_keys_str_mv AT hyunminkoo incongruencebetweendominantcommensaldonormicrobesinrecipientfecespostfecaltransplantandresponsetoantipd1immunotherapy
AT caseydmorrow incongruencebetweendominantcommensaldonormicrobesinrecipientfecespostfecaltransplantandresponsetoantipd1immunotherapy
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