Gastrointestinal tract involvement in systemic sclerosis: The roles of diet and the microbiome
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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.
Authors
Nguyen AD, Andréasson K, McMahan ZH, Bukiri H, Howlett N, Lagishetty V, Lee SM, Jacobs JP, Volkmann ER
Journal
Seminars in arthritis and rheumatism
Year
2023
Keywords:
FODMAP diet, Gastrointestinal microbiome, Systemic sclerosis, nutrition
BACKGROUND: Alterations in gastrointestinal (GI) microbial composition have been reported in patients with systemic sclerosis (SSc). However, it is unclear to what degree these alterations and/or dietary changes contribute to the SSc-GI phenotype. OBJECTIVES: Our study aimed to 1) evaluate the relationship between GI microbial composition and SSc-GI symptoms, and 2) compare GI symptoms and GI microbial composition between SSc patients adhering to a low versus non-low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet. METHODS: Adult SSc patients were consecutively recruited to provide stool specimens for bacterial 16S rRNA gene sequencing. Patients completed the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument (GIT 2.0) and the Diet History Questionnaire (DHQ) II and were classified as adhering to a low or non-low FODMAP diet. GI microbial differences were assessed using three metrics of alpha diversity (species richness, evenness, and phylogenetic diversity), as well as beta diversity (overall microbial composition). Differential abundance analysis was performed to identify specific genera associated with SSc-GI phenotype and low versus non-low FODMAP diet. RESULTS: Of the 66 total SSc patients included, the majority were women (n = 56) with a mean disease duration of 9.6 years. Thirty-five participants completed the DHQ II. Increased severity of GI symptoms (total GIT 2.0 score) was associated with decreased species diversity and differences in GI microbial composition. Specifically, pathobiont genera (e.g., Klebsiella and Enterococcus) were significantly more abundant in patients with increased GI symptom severity. When comparing low (N = 19) versus non-low (N = 16) FODMAP groups, there were no significant differences in GI symptom severity or in alpha and beta diversity. Compared with the low FODMAP group, the non-low FODMAP group had greater abundance of the pathobiont Enterococcus. CONCLUSION: SSc patients reporting more severe GI symptoms exhibited GI microbial dysbiosis characterized by less species diversity and alterations in microbial composition. A low FODMAP diet was not associated with significant alterations in GI microbial composition or reduced SSc-GI symptoms; however, randomized controlled trials are needed to evaluate the impact of specific diets on GI symptoms in SSc.
Experiment 1
Needs review
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
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- systemic scleroderma diffuse Scleroderma,diffuse sclerosis,Progressive systemic sclerosis,progressive systemic sclerosis,PSS (progressive systemic sclerosis),PSS - Progressive systemic sclerosis,Scleroderma,Scleroderma (& [systemic sclerosis]),Scleroderma syndrome,Scleroderma, diffuse,Scleroderma, Systemic,Scleroderma, systemic,Sclerosis, Systemic,SS - Systemic sclerosis,SSc,SSc, diffuse sclerosis,systemic Scleroderma,systemic scleroderma,Systemic sclerosis,systemic sclerosis,Systemic sclerosis (disorder),Thibierge-Weissenbach syndrome
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Adult Systemic Sclerosis patients on a low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet.
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Adult Systemic Sclerosis patients on a non-low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet.
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Adult patients with Systemic Sclerosis of any duration, as diagnosed according to the 2013 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Systemic Sclerosis, on a non-low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 19
- Group 1 sample size Number of subjects in the case (exposed) group
- 16
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- Three weeks
Lab analysis
- Sequencing type
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- V4-V4
- 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)
- 0.1
- 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
- unchanged
- Chao1 Abundance-based estimator of species richness
- unchanged
- Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
- unchanged
Signature 1
Needs review
Source: Figure 4
Description: Differential abundance of specific genera between low versus non-low FODMAP groups.
Abundance in Group 1: increased abundance in Adult Systemic Sclerosis patients on a non-low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet.
| NCBI | Quality Control | Links |
|---|---|---|
| Enterococcus | ||
| Klebsiella | ||
| Megasphaera | ||
| Rhodospirillales |
Signature 2
Source: Figure 4
Description: Differential abundance of specific genera between low versus non-low FODMAP groups.
Abundance in Group 1: decreased abundance in Adult Systemic Sclerosis patients on a non-low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet.
| NCBI | Quality Control | Links |
|---|---|---|
| Coprococcus sp. | ||
| Erysipelotrichaceae | ||
| Faecalibacterium sp. UBA1819 | ||
| Hungatella | ||
| Oribacterium | ||
| Peptoclostridium | ||
| Terrisporobacter | ||
| Tyzzerella sp. | ||
| uncultured Lachnospiraceae bacterium |
Experiment 2
Needs review
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Not Applicable
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Systemic Sclerosis patients with increased GIT 2.0 score
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Adult patients with Systemic Sclerosis of any duration, as diagnosed according to the 2013 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Systemic Sclerosis, reporting more severe Gastrointestinal Tract symptoms
- 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
- 66
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- four weeks
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
Signature 1
Needs review
Source: Figure 3
Description: Differential abundance of specific genera based on GIT 2.0 Total Score
Abundance in Group 1: increased abundance in Systemic Sclerosis patients with increased GIT 2.0 score
| NCBI | Quality Control | Links |
|---|---|---|
| Enterococcus | ||
| Faecalibacterium sp. UBA1819 | ||
| Klebsiella | ||
| Lactobacillus | ||
| Sphingobium |
Revision editor(s): Boadiwaa, Chloe, Hodan Issah
Signature 2
Needs review
Curated date: 2023/10/11
Curator: Boadiwaa
Revision editor(s): Boadiwaa, Chloe, Peace Sandy, Hodan Issah
Source: Figure 3
Description: Differential abundance of specific genera based on GIT 2.0 Total Score
Abundance in Group 1: decreased abundance in Systemic Sclerosis patients with increased GIT 2.0 score
Revision editor(s): Boadiwaa, Chloe, Peace Sandy, Hodan Issah
Experiment 3
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Not specified
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Systemic Sclerosis patients with more severe diarrhoea
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Adult patients with Systemic Sclerosis of any duration, as diagnosed according to the 2013 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Systemic Sclerosis, reporting more severe diarrhea based on the diarrhea score.
Lab analysis
Statistical Analysis
Alpha Diversity
- Chao1 Abundance-based estimator of species richness
- decreased
- Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
- decreased
Signature 1
Source: Supplemental Figure 1
Description: Differential abundance of specific genera based on symptom score for the diarrhea domain.
Abundance in Group 1: increased abundance in Systemic Sclerosis patients with more severe diarrhoea
| NCBI | Quality Control | Links |
|---|---|---|
| Enterococcus | ||
| Clostridiales bacterium DTU089 | ||
| Veillonella | ||
| Lactobacillus | ||
| Sphingobium |
Revision editor(s): Boadiwaa
Signature 2
Source: Supplemental Figure 1
Description: Differential abundance of specific genera based on symptom score for the diarrhea domain.
Abundance in Group 1: decreased abundance in Systemic Sclerosis patients with more severe diarrhoea
Revision editor(s): Boadiwaa
Experiment 4
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Systemic Sclerosis patients with worsened social functioning
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Adult patients with Systemic Sclerosis of any duration, as diagnosed according to the 2013 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Systemic Sclerosis, reporting worsened social functioning
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
Signature 1
Source: Supplemental Figure 2
Description: Differential abundance of specific genera based on symptom score for the social functioning domain.
Abundance in Group 1: increased abundance in Systemic Sclerosis patients with worsened social functioning
| NCBI | Quality Control | Links |
|---|---|---|
| Lactococcus | ||
| Megasphaera | ||
| Enterococcus | ||
| Faecalibacterium sp. UBA1819 | ||
| Hungatella | ||
| Escherichia | ||
| Shigella | ||
| Eggerthella | ||
| Lactobacillus | ||
| Lachnoclostridium | ||
| Sphingobium |
Revision editor(s): Boadiwaa
Signature 2
Source: Supplemental Figure 2
Description: Differential abundance of specific genera based on symptom score for the social functioning domain.
Abundance in Group 1: decreased abundance in Systemic Sclerosis patients with worsened social functioning
Revision editor(s): Boadiwaa
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