Metagenomic, metabolomic, and lipidomic shifts associated with fecal microbiota transplantation for recurrent Clostridioides difficile infection
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
McMillan AS, Zhang G, Dougherty MK, McGill SK, Gulati AS, Baker ES, Theriot CM
Journal
mSphere
Year
2024
Keywords:
Clostridioides difficile, acylcarnitines, amino acids, bile acids, bile salt hydrolase, fecal microbiota transplant, lipids, microbial conjugated bile acids
Recurrent C. difficile infection (rCDI) is an urgent public health threat, for which the last resort and lifesaving treatment is a fecal microbiota transplant (FMT). However, the exact mechanisms that mediate a successful FMT are not well-understood. Here, we use longitudinal stool samples collected from patients undergoing FMT to evaluate intra-individual changes in the microbiome, metabolome, and lipidome after successful FMTs relative to their baselines pre-FMT. We show changes in the abundance of many lipids, specifically a decrease in acylcarnitines post-FMT, and a shift from conjugated bile acids pre-FMT to deconjugated secondary bile acids post-FMT. These changes correlate with a decrease in Enterobacteriaceae, which encode carnitine metabolism genes, and an increase in Lachnospiraceae, which encode bile acid altering genes such as bile salt hydrolases (BSHs) and the bile acid-inducible (bai) operon, post-FMT. We also show changes in gut microbe-encoded amino acid biosynthesis genes, of which Enterobacteriaceae was the primary contributor to amino acids C. difficile is auxotrophic for. Liquid chromatography, ion mobility spectrometry, and mass spectrometry (LC-IMS-MS) revealed a shift from microbial conjugation of primary bile acids pre-FMT to secondary bile acids post-FMT. Here, we define the structural and functional changes associated with a successful FMT and generate hypotheses that require further experimental validation. This information is meant to help guide the development of new microbiota-focused therapeutics to treat rCDI.IMPORTANCERecurrent C. difficile infection is an urgent public health threat, for which the last resort and lifesaving treatment is a fecal microbiota transplant. However, the exact mechanisms that mediate a successful FMT are not well-understood. Here, we show changes in the abundance of many lipids, specifically acylcarnitines and bile acids, in response to FMT. These changes correlate with Enterobacteriaceae pre-FMT, which encodes carnitine metabolism genes, and Lachnospiraceae post-FMT, which encodes bile salt hydrolases and baiA genes. There was also a shift from microbial conjugation of primary bile acids pre-FMT to secondary bile acids post-FMT. Here, we define the structural and functional changes associated with a successful FMT, which we hope will help aid in the development of new microbiota-focused therapeutics to treat rCDI.
Experiment 1
Reviewed Marked as Reviewed by Svetlana up on 2025-1-10
Subjects
- Location of subjects
- United States of America
- Host species Species from which microbiome was sampled. Contact us to have more species added.
- 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,feces
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Clostridium difficile infection clostridium difficile disease,Clostridium difficile infection,clostridium difficile infection
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- pre-Fecal Microbiota Transplant (pre-FMT)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- post-Fecal Microbiota Transplant (post-FMT - 2 weeks)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- post-FMT (2 weeks) refers to samples from patients at 2weeks of fecal microbiota transplant (FMT).
- Group 0 sample size Number of subjects in the control (unexposed) group
- 16
- Group 1 sample size Number of subjects in the case (exposed) group
- 11
Lab analysis
- Sequencing type
- WMS
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- Not specified
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Illumina
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- log transformation
- Statistical test
- MaAsLin2
- 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)?
- Yes
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- increased
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-1-10
Source: Table S1
Description: Differential abundance of microbiota between pre-FMT patients and 2-weeks post-FMT patients.
Abundance in Group 1: increased abundance in post-Fecal Microbiota Transplant (post-FMT - 2 weeks)
| NCBI | Quality Control | Links |
|---|---|---|
| Acutalibacteraceae | ||
| Anaerovoracaceae | ||
| Bacteroidaceae | ||
| Bifidobacteriaceae | ||
| Butyricicoccaceae | ||
| Coriobacteriaceae | ||
| Eggerthellaceae | ||
| Lachnospiraceae | ||
| Oscillospiraceae |
Revision editor(s): KateRasheed
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2025-1-10
Source: Table S1
Description: Differential abundance of microbiota between pre-FMT patients and 2-weeks post-FMT patients.
Abundance in Group 1: decreased abundance in post-Fecal Microbiota Transplant (post-FMT - 2 weeks)
| NCBI | Quality Control | Links |
|---|---|---|
| Enterobacteriaceae | ||
| Veillonellaceae |
Revision editor(s): KateRasheed
Experiment 2
Reviewed Marked as Reviewed by Svetlana up on 2025-1-10
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- pre-FMT
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- post-FMT (2 months)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- post-FMT (2 months) refers to samples from patients at 2 months of fecal microbiota transplant (FMT).
- Group 1 sample size Number of subjects in the case (exposed) group
- 10
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- increased
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-1-10
Source: Table S1
Description: Differential abundance of microbiota between pre-FMT patients and 2-months post-FMT patients.
Abundance in Group 1: increased abundance in post-FMT (2 months)
| NCBI | Quality Control | Links |
|---|---|---|
| Acutalibacteraceae | ||
| Oscillospiraceae | ||
| Eggerthellaceae | ||
| Coriobacteriaceae | ||
| Lachnospiraceae | ||
| Bacteroidaceae | ||
| Anaerovoracaceae | ||
| Butyricicoccaceae |
Revision editor(s): KateRasheed
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2025-1-10
Source: Table S1
Description: Differential abundance of microbiota between pre-FMT patients and 2-months post-FMT patients.
Abundance in Group 1: decreased abundance in post-FMT (2 months)
| NCBI | Quality Control | Links |
|---|---|---|
| Enterobacteriaceae | ||
| Veillonellaceae | ||
| Lactobacillaceae |
Revision editor(s): KateRasheed
Experiment 3
Reviewed Marked as Reviewed by Svetlana up on 2025-1-10
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- post-FMT (6 months)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- post-FMT (6 months) refers to samples from patients at 6 months of fecal microbiota transplant (FMT).
- Group 1 sample size Number of subjects in the case (exposed) group
- 8
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- increased
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-1-10
Source: Table S1
Description: Differential abundance of microbiota between pre-FMT patients and 6-months post-FMT patients.
Abundance in Group 1: increased abundance in post-FMT (6 months)
| NCBI | Quality Control | Links |
|---|---|---|
| Acutalibacteraceae | ||
| Anaerovoracaceae | ||
| Bacteroidaceae | ||
| Coriobacteriaceae | ||
| Eggerthellaceae | ||
| Lachnospiraceae | ||
| Oscillospiraceae | ||
| Faecalibacterium sp. CAG:74 |
Revision editor(s): KateRasheed
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2025-1-10
Source: Table S1
Description: Differential abundance of microbiota between pre-FMT patients and 6-months post-FMT patients.
Abundance in Group 1: decreased abundance in post-FMT (6 months)
| NCBI | Quality Control | Links |
|---|---|---|
| Enterobacteriaceae | ||
| Lactobacillaceae |
Revision editor(s): KateRasheed
Experiment 4
Reviewed Marked as Reviewed by Svetlana up on 2025-1-10
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- post-FMT (all time points)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- post-FMT refers to all post-FMT time points (2 week, 2 months, and 6 months)
- Group 1 sample size Number of subjects in the case (exposed) group
- 29
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- increased
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-1-10
Source: Table S1
Description: Differential abundance of microbiota between pre-FMT and all post-FMT patients.
Abundance in Group 1: increased abundance in post-FMT (all time points)
| NCBI | Quality Control | Links |
|---|---|---|
| Acutalibacteraceae | ||
| Anaerovoracaceae | ||
| Bacteroidaceae | ||
| Bifidobacteriaceae | ||
| Butyricicoccaceae | ||
| Coriobacteriaceae | ||
| Eggerthellaceae | ||
| Lachnospiraceae | ||
| Oscillospiraceae | ||
| Rikenellaceae |
Revision editor(s): KateRasheed
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2025-1-10
Source: Table S1
Description: Differential abundance of microbiota between pre-FMT and all post-FMT patients.
Abundance in Group 1: decreased abundance in post-FMT (all time points)
| NCBI | Quality Control | Links |
|---|---|---|
| Enterobacteriaceae | ||
| Enterococcaceae | ||
| Veillonellaceae | ||
| MegasphaeraceaeMegasphaeraceae | ||
| Lactobacillaceae |
Revision editor(s): KateRasheed
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