Third-party fecal microbiota transplantation following allo-HCT reconstitutes microbiome diversity

From BugSigDB
Reviewed Marked as Reviewed by Rimsha Azhar on 2021/02/09
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
Authors
DeFilipp Z, Peled JU, Li S, Mahabamunuge J, Dagher Z, Slingerland AE, Del Rio C, Valles B, Kempner ME, Smith M, Brown J, Dey BR, El-Jawahri A, McAfee SL, Spitzer TR, Ballen KK, Sung AD, Dalton TE, Messina JA, Dettmer K, Liebisch G, Oefner P, Taur Y, Pamer EG, Holler E, Mansour MK, van den Brink MRM, Hohmann E, Jenq RR, Chen YB
Journal
Blood advances
Year
2018
We hypothesized that third-party fecal microbiota transplantation (FMT) may restore intestinal microbiome diversity after allogeneic hematopoietic cell transplantation (allo-HCT). In this open-label single-group pilot study, 18 subjects were enrolled before allo-HCT and planned to receive third-party FMT capsules. FMT capsules were administered no later than 4 weeks after neutrophil engraftment, and antibiotics were not allowed within 48 hours before FMT. Five patients did not receive FMT because of the development of early acute gastrointestinal (GI) graft-versus-host disease (GVHD) before FMT (n = 3), persistent HCT-associated GI toxicity (n = 1), or patient decision (n = 1). Thirteen patients received FMT at a median of 27 days (range, 19-45 days) after HCT. Participants were able to swallow and tolerate all FMT capsules, meeting the primary study endpoint of feasibility. FMT was tolerated well, with 1 treatment-related significant adverse event (abdominal pain). Two patients subsequently developed acute GI GVHD, with 1 patient also having concurrent bacteremia. No additional cases of bacteremia occurred. Median follow-up for survivors is 15 months (range, 13-20 months). The Kaplan-Meier estimates for 12-month overall survival and progression-free survival after FMT were 85% (95% confidence interval, 51%-96%) and 85% (95% confidence interval, 51%-96%), respectively. There was 1 nonrelapse death resulting from acute GI GVHD (12-month nonrelapse mortality, 8%; 95% confidence interval, 0%-30%). Analysis of stool composition and urine 3-indoxyl sulfate concentration indicated improvement in intestinal microbiome diversity after FMT that was associated with expansion of stool-donor taxa. These results indicate that empiric third-party FMT after allo-HCT appears to be feasible, safe, and associated with expansion of recipient microbiome diversity. This trial was registered at www.clinicaltrials.gov as #NCT02733744.

Experiment 1


Reviewed Marked as Reviewed by Rimsha Azhar on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks

Subjects

Location of subjects
United States of America
Host species Species from which microbiome was sampled (if applicable)
Homo sapiens
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
response to allogeneic hematopoietic stem cell transplant response to allogeneic hematopoietic stem cell transplant
Group 0 name Corresponds to the control (unexposed) group for case-control studies
patients post allogenic hematopoietic cell transplant/pre Fecal Microbiota Transplant
Group 1 name Corresponds to the case (exposed) group for case-control studies
patients preallogenic hematopoietic cell transplant
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
patients who received Fecal Microbiome Transplant
Group 0 sample size Number of subjects in the control (unexposed) group
5
Group 1 sample size Number of subjects in the case (exposed) group
13
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
48 hours

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V4-V5
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Statistical test
Mann-Whitney (Wilcoxon)
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
No
Matched on Factors on which subjects have been matched on in a case-control study
age
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, HLA match, transplant conditioning, Confounders controlled for: "history of GI infection" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.history of GI infection, acute graft vs. host disease

Alpha Diversity

Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
increased

Signature 1

Reviewed Marked as Reviewed by Rimsha Azhar on 2021/02/09

Curated date: 2021/01/10

Curator: Nadine Ulysse

Revision editor(s): WikiWorks

Source: Figure 4B

Description: Third-party fecal microbiota transplantation (FMT) may restore intestinal microbiome diversity after allogeneic hematopoietic cell transplantation (allo-HCT)

Abundance in Group 1: increased abundance in patients preallogenic hematopoietic cell transplant

NCBI Links
Eubacteriales

Revision editor(s): WikiWorks

Experiment 2


Reviewed Marked as Reviewed by Rimsha Azhar on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks

Subjects

Location of subjects
United States of America
Host species Species from which microbiome was sampled (if applicable)
Homo sapiens
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
response to allogeneic hematopoietic stem cell transplant response to allogeneic hematopoietic stem cell transplant
Group 0 name Corresponds to the control (unexposed) group for case-control studies
post fecal mircobiota day 180
Group 1 name Corresponds to the case (exposed) group for case-control studies
post allogenic hematopoietic cell transplant/ pre Fecal microbiota transplant
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
patients who received Fecal Microbiome Transplant
Group 0 sample size Number of subjects in the control (unexposed) group
5
Group 1 sample size Number of subjects in the case (exposed) group
13
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
48 hours

Lab analysis

Sequencing type
16S
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Statistical test
Mann-Whitney (Wilcoxon)
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
No
Matched on Factors on which subjects have been matched on in a case-control study
age
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, HLA match, transplant conditioning, Confounders controlled for: "history of GI infection" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.history of GI infection, acute graft vs. host disease

Alpha Diversity

Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
unchanged

Signature 1

Reviewed Marked as Reviewed by Rimsha Azhar on 2021/02/09

Curated date: 2021/01/10

Curator: Nadine Ulysse

Revision editor(s): WikiWorks

Source: Figure 4B

Description: Third-party fecal microbiota transplantation (FMT) may restore intestinal microbiome diversity after allogeneic hematopoietic cell transplantation (allo-HCT)

Abundance in Group 1: decreased abundance in post allogenic hematopoietic cell transplant/ pre Fecal microbiota transplant

NCBI Links
Eubacteriales

Revision editor(s): WikiWorks

Experiment 3


Reviewed Marked as Reviewed by Rimsha Azhar on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks

Subjects

Location of subjects
United States of America
Host species Species from which microbiome was sampled (if applicable)
Homo sapiens
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
response to allogeneic hematopoietic stem cell transplant response to allogeneic hematopoietic stem cell transplant
Group 0 name Corresponds to the control (unexposed) group for case-control studies
post fecal mircobiota day 7
Group 1 name Corresponds to the case (exposed) group for case-control studies
post allogenic hematopoietic cell transplant/ pre Fecal microbiota transplant
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
patients who received Fecal Microbiome Transplant
Group 0 sample size Number of subjects in the control (unexposed) group
5
Group 1 sample size Number of subjects in the case (exposed) group
13
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
48 hours

Lab analysis

Sequencing type
16S
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Statistical test
Mann-Whitney (Wilcoxon)
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
No
Matched on Factors on which subjects have been matched on in a case-control study
age
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, HLA match, transplant conditioning, Confounders controlled for: "history of GI infection" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.history of GI infection, acute graft vs. host disease

Alpha Diversity

Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
decreased

Signature 1

Reviewed Marked as Reviewed by Rimsha Azhar on 2021/02/09

Curated date: 2021/01/10

Curator: Nadine Ulysse

Revision editor(s): WikiWorks

Source: Figure 5

Description: Third-party fecal microbiota transplantation (FMT) may restore intestinal microbiome diversity after allogeneic hematopoietic cell transplantation (allo-HCT)

Abundance in Group 1: decreased abundance in post allogenic hematopoietic cell transplant/ pre Fecal microbiota transplant

NCBI Links
Eubacteriales

Revision editor(s): WikiWorks

Experiment 4


Reviewed Marked as Reviewed by Rimsha Azhar on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks

Subjects

Location of subjects
United States of America
Host species Species from which microbiome was sampled (if applicable)
Homo sapiens
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
response to allogeneic hematopoietic stem cell transplant response to allogeneic hematopoietic stem cell transplant
Group 0 name Corresponds to the control (unexposed) group for case-control studies
post fecal mircobiota day 30
Group 1 name Corresponds to the case (exposed) group for case-control studies
post allogenic hematopoietic cell transplant/ pre Fecal microbiota transplant
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
patients who received Fecal Microbiome Transplant
Group 0 sample size Number of subjects in the control (unexposed) group
5
Group 1 sample size Number of subjects in the case (exposed) group
13
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
48 hours

Lab analysis

Sequencing type
16S
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Statistical test
Mann-Whitney (Wilcoxon)
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
No
Matched on Factors on which subjects have been matched on in a case-control study
age
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, HLA match, transplant conditioning, Confounders controlled for: "hx of GI infection" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.hx of GI infection, acute graft vs. host disease

Alpha Diversity

Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
decreased

Signature 1

Reviewed Marked as Reviewed by Rimsha Azhar on 2021/02/09

Curated date: 2021/01/10

Curator: Nadine Ulysse

Revision editor(s): WikiWorks

Source: Figure 5

Description: Third-party fecal microbiota transplantation (FMT) may restore intestinal microbiome diversity after allogeneic hematopoietic cell transplantation (allo-HCT)

Abundance in Group 1: decreased abundance in post allogenic hematopoietic cell transplant/ pre Fecal microbiota transplant

NCBI Links
Eubacteriales

Revision editor(s): WikiWorks