Faecal microbial transfer and complex carbohydrates mediate protection against COPD
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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
Budden KF, Shukla SD, Bowerman KL, Vaughan A, Gellatly SL, Wood DLA, Lachner N, Idrees S, Rehman SF, Faiz A, Patel VK, Donovan C, Alemao CA, Shen S, Amorim N, Majumder R, Vanka KS, Mason J, Haw TJ, Tillet B, Fricker M, Keely S, Hansbro N, Belz GT, Horvat J, Ashhurst T, van Vreden C, McGuire H, Fazekas de St Groth B, King NJC, Crossett B, Cordwell SJ, Bonaguro L, Schultze JL, Hamilton-Williams EE, Mann E, Forster SC, Cooper MA, Segal LN, Chotirmall SH, Collins P, Bowman R, Fong KM, Yang IA, Wark PAB, Dennis PG, Hugenholtz P, Hansbro PM
Journal
Gut
Year
2024
Keywords:
BASIC SCIENCES, COLONIC MICROFLORA, DIETARY FIBRE, IMMUNOLOGY, INFLAMMATORY DISEASES
OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a major cause of global illness and death, most commonly caused by cigarette smoke. The mechanisms of pathogenesis remain poorly understood, limiting the development of effective therapies. The gastrointestinal microbiome has been implicated in chronic lung diseases via the gut-lung axis, but its role is unclear. DESIGN: Using an in vivo mouse model of cigarette smoke (CS)-induced COPD and faecal microbial transfer (FMT), we characterised the faecal microbiota using metagenomics, proteomics and metabolomics. Findings were correlated with airway and systemic inflammation, lung and gut histopathology and lung function. Complex carbohydrates were assessed in mice using a high resistant starch diet, and in 16 patients with COPD using a randomised, double-blind, placebo-controlled pilot study of inulin supplementation. RESULTS: FMT alleviated hallmark features of COPD (inflammation, alveolar destruction, impaired lung function), gastrointestinal pathology and systemic immune changes. Protective effects were additive to smoking cessation, and transfer of CS-associated microbiota after antibiotic-induced microbiome depletion was sufficient to increase lung inflammation while suppressing colonic immunity in the absence of CS exposure. Disease features correlated with the relative abundance of Muribaculaceae, Desulfovibrionaceae and Lachnospiraceae family members. Proteomics and metabolomics identified downregulation of glucose and starch metabolism in CS-associated microbiota, and supplementation of mice or human patients with complex carbohydrates improved disease outcomes. CONCLUSION: The gut microbiome contributes to COPD pathogenesis and can be targeted therapeutically.
Experiment 1
Needs review
Subjects
- Location of subjects
- Australia
- Host species Species from which microbiome was sampled. Contact us to have more species added.
- Mus musculus
- 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
- Response to transplant Response to transplant,response to transplant
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Air-exposed FMT mice - 12 weeks
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Cigarette Smoke exposed FMT mice (CS-exposed 12 weeks)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Cigarette Smoke exposed FMT mice (CS-exposed 12 weeks) refers to "in vivo" female mouse model of cigarette smoke (CS)-induced COPD and faecal microbial transfer (FMT) who underwent 3 weeks of baseline microbiome normalisation by transferring soiled bedding and co-housing, before exposure to mainstream CS through the nose only for 12 weeks (12 wk CS).
- Group 0 sample size Number of subjects in the control (unexposed) group
- 8
- Group 1 sample size Number of subjects in the case (exposed) group
- 8
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).
- raw counts
- Statistical test
- DESeq2
- 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
- Matched on Factors on which subjects have been matched on in a case-control study
- age
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- 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
Needs review
Source: Supplementary Table 6
Description: Differential abundant taxa between air-exposed FMT mice and CS-exposed FMT mice at 12 weeks
Abundance in Group 1: decreased abundance in Cigarette Smoke exposed FMT mice (CS-exposed 12 weeks)
| NCBI | Quality Control | Links |
|---|---|---|
| Lachnospiraceae | ||
| Muricomes sp. | ||
| Kineothrix sp. |
Revision editor(s): KateRasheed
Signature 2
Needs review
Source: Supplementary Table 6
Description: Differential abundant taxa between air-exposed FMT mice and CS-exposed FMT mice at 12 weeks
Abundance in Group 1: increased abundance in Cigarette Smoke exposed FMT mice (CS-exposed 12 weeks)
Revision editor(s): KateRasheed
Experiment 2
Needs review
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- 8weeks CS exposed + 4weeks rest FMT mice
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- 8weeks CS exposed + 4weeks rest FMT mice refers to mice who were induced with cigarette-smoke(CS) for 8weeks after which they were exposed to normal air for 4weeks.
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- 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
Needs review
Source: Supplementary Table 6
Description: Differential abundant taxa between 12 weeks air-exposed FMT mice and 8weeks CS exposed + 4weeks rest FMT mice
Abundance in Group 1: decreased abundance in 8weeks CS exposed + 4weeks rest FMT mice
| NCBI | Quality Control | Links |
|---|---|---|
| Lactobacillus johnsonii | ||
| COE1 sp009774375COE1 sp009774375 | ||
| Alistipes sp. | ||
| Muricomes sp. |
Revision editor(s): KateRasheed
Signature 2
Needs review
Source: Supplementary Table 6
Description: Differential abundant taxa between 12 weeks air-exposed FMT mice and 8weeks CS exposed + 4weeks rest FMT mice
Abundance in Group 1: increased abundance in 8weeks CS exposed + 4weeks rest FMT mice
Revision editor(s): KateRasheed
Experiment 3
Needs review
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Fecal samples baseline(Week 0)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Fecal samples at the end of the experiment(Week 12)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Fecal samples at the end of the experiment(Week 12) refers to fecal samples collected at the completion of the experiment.
- Group 0 sample size Number of subjects in the control (unexposed) group
- Not specified
- Group 1 sample size Number of subjects in the case (exposed) group
- Not specified
Lab analysis
Statistical Analysis
- Matched on Factors on which subjects have been matched on in a case-control study
- Not specified
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- increased
- 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
Needs review
Source: Supplementary Table 5
Description: Differentially abundant taxa between fecal samples at baseline(Week 0) and at completion of the experiment(Week 12)
Abundance in Group 1: increased abundance in Fecal samples at the end of the experiment(Week 12)
Revision editor(s): KateRasheed
Signature 2
Needs review
Source: Supplementary Table 5
Description: Differentially abundant taxa between fecal samples at baseline(Week 0) and at completion of the experiment(Week 12)
Abundance in Group 1: decreased abundance in Fecal samples at the end of the experiment(Week 12)
Revision editor(s): KateRasheed
Experiment 4
Needs review
Differences from previous experiment shown
Subjects
- Host species Species from which microbiome was sampled. Contact us to have more species added.
- Homo sapiens
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Treatment Treatment,treatment
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Pre-inulin
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Post-inulin
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Post-inulin refers to the period after inulin supplementation. Human patients with COPD received supplements of inulin, a common fermentable fibre, for 4 weeks.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 7
- Group 1 sample size Number of subjects in the case (exposed) group
- 9
Lab analysis
- Sequencing type
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- V5-V8
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- centered log-ratio
- Statistical test
- PLS-DA (Partial least square discriminant analysis)
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- No
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- 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
Needs review
Source: Figure 9D
Description: Differentially abundant taxa between pre-inulin and post inulin
Abundance in Group 1: increased abundance in Post-inulin
| NCBI | Quality Control | Links |
|---|---|---|
| uncultured bacterium | ||
| Erysipelotrichaceae | ||
| Intestinibacter | ||
| uncultured organism |
Revision editor(s): KateRasheed
Experiment 5
Needs review
Differences from previous experiment shown
Subjects
- Host species Species from which microbiome was sampled. Contact us to have more species added.
- Mus musculus
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Response to transplant Response to transplant,response to transplant
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Air-exposed control mice - 8 weeks
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Cigarette Smoke exposed control mice (CS-exposed control mice - 8 weeks)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Cigarette Smoke exposed control mice (CS-exposed control mice - 8 weeks) refers to mice model who received their own soiled bedding mixed with clean bedding for eight weeks.
- Group 0 sample size Number of subjects in the control (unexposed) group
- Not specified
- Group 1 sample size Number of subjects in the case (exposed) group
- Not specified
Lab analysis
Statistical Analysis
- Matched on Factors on which subjects have been matched on in a case-control study
- age
Signature 1
Needs review
Source: Figure S7e
Description: Differentially abundant taxa between air-exposed control mice and CS-exposed control mice
Abundance in Group 1: increased abundance in Cigarette Smoke exposed control mice (CS-exposed control mice - 8 weeks)
| NCBI | Quality Control | Links |
|---|---|---|
| Muribaculaceae |
Revision editor(s): KateRasheed
Signature 2
Needs review
Source: Figure S7e
Description: Differentially abundant taxa between air-exposed control mice and CS-exposed control mice at 8weeks.
Abundance in Group 1: decreased abundance in Cigarette Smoke exposed control mice (CS-exposed control mice - 8 weeks)
| NCBI | Quality Control | Links |
|---|---|---|
| Muribaculaceae | ||
| Eubacterium xylanophilum | ||
| Ruminococcus |
Revision editor(s): KateRasheed
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