Visceral adiposity in postmenopausal women is associated with a pro-inflammatory gut microbiome and immunogenic metabolic endotoxemia
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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
Gaber M, Wilson AS, Millen AE, Hovey KM, LaMonte MJ, Wactawski-Wende J, Ochs-Balcom HM, Cook KL
Journal
Microbiome
Year
2024
Keywords:
Aging, Inflammation, Leaky gut, Lipopolysaccharide, Menopause, Metabolic endotoxemia, Microbiome, Obesity, Women’s Health Initiative
BACKGROUND: Obesity, and in particular abdominal obesity, is associated with an increased risk of developing a variety of chronic diseases. Obesity, aging, and menopause are each associated with differential shifts in the gut microbiome. Obesity causes chronic low-grade inflammation due to increased lipopolysaccharide (LPS) levels which is termed "metabolic endotoxemia." We examined the association of visceral adiposity tissue (VAT) area, circulating endotoxemia markers, and the gut bacterial microbiome in a cohort of aged postmenopausal women. METHODS: Fifty postmenopausal women (mean age 78.8 ± 5.3 years) who had existing adipose measurements via dual x-ray absorptiometry (DXA) were selected from the extremes of VAT: n = 25 with low VAT area (45.6 ± 12.5 cm2) and n = 25 with high VAT area (177.5 ± 31.3 cm2). Dietary intake used to estimate the Healthy Eating Index (HEI) score was assessed with a food frequency questionnaire. Plasma LPS, LPS-binding protein (LBP), anti-LPS antibodies, anti-flagellin antibodies, and anti-lipoteichoic acid (LTA) antibodies were measured by ELISA. Metagenomic sequencing was performed on fecal DNA. Female C57BL/6 mice consuming a high-fat or low-fat diet were treated with 0.4 mg/kg diet-derived fecal isolated LPS modeling metabolic endotoxemia, and metabolic outcomes were measured after 6 weeks. RESULTS: Women in the high VAT group showed increased Proteobacteria abundance and a lower Firmicutes/Bacteroidetes ratio. Plasma LBP concentration was positively associated with VAT area. Plasma anti-LPS, anti-LTA, and anti-flagellin IgA antibodies were significantly correlated with adiposity measurements. Women with high VAT showed significantly elevated LPS-expressing bacteria compared to low VAT women. Gut bacterial species that showed significant associations with both adiposity and inflammation (anti-LPS IgA and LBP) were Proteobacteria (Escherichia coli, Shigella spp., and Klebsiella spp.) and Veillonella atypica. Healthy eating index (HEI) scores negatively correlated with % body fat and anti-LPS IgA antibodies levels. Preclinical murine model showed that high-fat diet-fed mice administered a low-fat diet fecal-derived LPS displayed reduced body weight, decreased % body fat, and improved glucose tolerance test parameters when compared with saline-injected or high-fat diet fecal-derived LPS-treated groups consuming a high-fat diet. CONCLUSIONS: Increased VAT in postmenopausal women is associated with elevated gut Proteobacteria abundance and immunogenic metabolic endotoxemia markers. Low-fat diet-derived fecal-isolated LPS improved metabolic parameters in high-fat diet-fed mice giving mechanistic insights into potential pro-health signaling mediated by under-acylated LPS isoforms. Video Abstract.
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,feces
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Visceral adipose tissue measurement , Gut microbiome measurement Visceral adipose tissue measurement,visceral adipose tissue measurement,Gut microbiome measurement,gut microbiome measurement
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Low VAT group (Control/Unexposed group).
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- High VAT group (Case/Exposed group)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- The high VAT group represents women with elevated visceral adipose tissue, which is associated with pro-inflammatory gut microbiome characteristics and metabolic endotoxemia
- Group 0 sample size Number of subjects in the control (unexposed) group
- 25
- Group 1 sample size Number of subjects in the case (exposed) group
- 25
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- Participants with detectable antibiotics in plasma were excluded from the analysis to prevent confounding effects on gut microbiome composition. This included antibiotics like amoxicillin and clindamycin.
Lab analysis
- Sequencing type
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- V3-V9
- 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
- LEfSe
- Mann-Whitney (Wilcoxon)
- PERMANOVA
- 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
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 2.0
- Matched on Factors on which subjects have been matched on in a case-control study
- Matched on: "VAT (visceral adipose tissue) area" 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.VAT (visceral adipose tissue) area
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- Confounders controlled for: "antibiotic use" 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.antibiotic use, Confounders controlled for: "dietary intake" 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.dietary intake, Confounders controlled for: "hormone therapy usage" 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.hormone therapy usage
Alpha Diversity
- Pielou Quantifies how equal the community is numerically
- unchanged
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- increased
- Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
- increased
- Richness Number of species
- unchanged
- Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
- unchanged
Signature 1
Needs review
Source: Fecal microbiome of postmenopausal women
Description: Increased abundance of Proteobacteria, a phylum of gram-negative bacteria linked to inflammation, in women with high visceral adiposity tissue (VAT).
Abundance in Group 1: increased abundance in High VAT group (Case/Exposed group)
| NCBI | Quality Control | Links |
|---|---|---|
| Enterobacteriaceae | ||
| Escherichia coli | ||
| Pseudomonadota | ||
| Enterobacter | ||
| Klebsiella | ||
| Salmonella |
Revision editor(s): Vandana Maddi
Signature 2
Needs review
Source: Fecal microbiome of postmenopausal women
Description: Decreased Firmicutes/Bacteroidetes ratio, which is often associated with metabolic imbalance and obesity, in the high VAT group.
Abundance in Group 1: decreased abundance in High VAT group (Case/Exposed group)
| NCBI | Quality Control | Links |
|---|---|---|
| Bacillota | ||
| Bacteroides | ||
| Ruminococcaceae sp. B_A14 | ||
| Prevotella | ||
| Clostridium |
Revision editor(s): Vandana Maddi
Experiment 2
Needs review
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Human gut metagenome human gut microbiota,Human gut metagenome,human gut metagenome
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Low LPS levels
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- High LPS levels
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Elevated plasma LPS levels
- Group 0 sample size Number of subjects in the control (unexposed) group
- 23
- Group 1 sample size Number of subjects in the case (exposed) group
- 24
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- Yes
Lab analysis
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- V6-V9
Statistical Analysis
- Statistical test
- T-Test
- Matched on Factors on which subjects have been matched on in a case-control study
- Matched on: "Age" 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.Age, Matched on: "BMI" 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.BMI
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- Confounders controlled for: "Smoking" 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.Smoking, Confounders controlled for: "medication usge" 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.medication usge
Alpha Diversity
- Pielou Quantifies how equal the community is numerically
- decreased
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Chao1 Abundance-based estimator of species richness
- decreased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- decreased
- Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
- decreased
- Richness Number of species
- decreased
- Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
- decreased
Signature 1
Needs review
Source: Gut microbiome
Description: Elevated Shigella, a genus associated with gut infections and endotoxemia, in participants with high LPS levels and adiposity.
Abundance in Group 1: increased abundance in High LPS levels
| NCBI | Quality Control | Links |
|---|---|---|
| Shigella boydii | ||
| Salmonella | ||
| Klebsiella pneumoniae |
Revision editor(s): Vandana Maddi
Signature 2
Needs review
Source: Gut microbiome
Description: Reduced levels of Alistipes, a gut microbe linked to anti-inflammatory properties, in the high LPS group.
Abundance in Group 1: decreased abundance in High LPS levels
| NCBI | Quality Control | Links |
|---|---|---|
| Faecalibacterium | ||
| Alistipes | ||
| Bacteroides uniformis |
Revision editor(s): Vandana Maddi
Experiment 3
Needs review
Differences from previous experiment shown
Subjects
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Feces , Large intestine 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,Intestinum crassum,Large intestine,large intestine
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- IGA glomerulonephritis Berger Disease,Berger's Disease,berger's disease,berger's IgA or IgG nephropathy,focal glomerulonephritis,Glomerulonephritis, IGA,IgA glomerulonephritis,IGA Nephropathy,IgA nephropathy,Immunoglobulin A Nephropathy,Nephropathy, IGA,primary IgA nephropathy,segmental glomerulonephritis,IGA glomerulonephritis,iGA glomerulonephritis
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Low IgA response
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- High IgA response
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Elevated anti-LPS IgA levels
Lab analysis
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- V3-V9
Statistical Analysis
- Statistical test
- Pearson Correlation
- Matched on Factors on which subjects have been matched on in a case-control study
- Matched on: "BMI" 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.BMI
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- diet, Confounders controlled for: "antibiotic use" 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.antibiotic use
Alpha Diversity
- Pielou Quantifies how equal the community is numerically
- increased
- Shannon Estimator of species richness and species evenness: more weight on species richness
- increased
- Chao1 Abundance-based estimator of species richness
- increased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- increased
- Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
- increased
- Richness Number of species
- increased
- Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
- increased
Signature 1
Needs review
Source: Gut microbiome
Description: Increased Escherichia coli, a gram-negative bacterium linked to inflammation, in the high IgA response group, indicating heightened immune activation.
Abundance in Group 1: increased abundance in High IgA response
| NCBI | Quality Control | Links |
|---|---|---|
| Escherichia coli | ||
| Klebsiella oxytoca | ||
| Shigella flexneri |
Revision editor(s): Vandana Maddi
Signature 2
Needs review
Source: Gut microbiome
Description: Decreased abundance of Lachnospiraceae, a family associated with short-chain fatty acid production and gut health, in the high IgA group.
Abundance in Group 1: decreased abundance in High IgA response
| NCBI | Quality Control | Links |
|---|---|---|
| Lachnospiraceae | ||
| Blautia | ||
| Coprococcus |
Revision editor(s): Vandana Maddi
Experiment 4
Needs review
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Eating behaviour Eating behaviour,eating behaviour
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Low HEI group
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- High HEI group
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- HEI score ≥ 70
- Group 0 sample size Number of subjects in the control (unexposed) group
- 25
- Group 1 sample size Number of subjects in the case (exposed) group
- 25
Lab analysis
Statistical Analysis
- Statistical test
- Mann-Whitney (Wilcoxon)
- Matched on Factors on which subjects have been matched on in a case-control study
- age, Matched on: "BMI" 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.BMI
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- physical activity, Confounders controlled for: "smoking" 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.smoking
Alpha Diversity
- Pielou Quantifies how equal the community is numerically
- increased
- Shannon Estimator of species richness and species evenness: more weight on species richness
- increased
- Chao1 Abundance-based estimator of species richness
- increased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- increased
- Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
- increased
- Richness Number of species
- increased
- Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
- increased
Signature 1
Needs review
Source: Plasma microbiome
Description: Elevated Veillonella atypica, a bacterium linked to systemic inflammation and gut dysbiosis, in individuals with high LBP concentrations.
Abundance in Group 1: increased abundance in High HEI group
| NCBI | Quality Control | Links |
|---|---|---|
| Veillonella atypica | ||
| Streptococcus | ||
| Megasphaera |
Revision editor(s): Vandana Maddi
Signature 2
Needs review
Source: Plasma microbiome
Description: Reduced Barnesiella, a beneficial gut microbe, in the high LBP group, suggesting an imbalance in microbial composition.
Abundance in Group 1: decreased abundance in High HEI group
| NCBI | Quality Control | Links |
|---|---|---|
| Barnesiella | ||
| Bifidobacterium | ||
| Akkermansia |
Revision editor(s): Vandana Maddi
Experiment 5
Needs review
Differences from previous experiment shown
Subjects
- 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
- Plasma Cell Count PLSTCE,Total Plasma Cells,Plasma Cell Count,plasma Cell Count
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Low Plasma LBP group
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- High Plasma LBP group
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Elevated plasma LBP concentration
- Group 0 sample size Number of subjects in the control (unexposed) group
- 23
- Group 1 sample size Number of subjects in the case (exposed) group
- 24
Lab analysis
Statistical Analysis
- Statistical test
- Pearson Correlation
- Matched on Factors on which subjects have been matched on in a case-control study
- age, Matched on: "total body fat" 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.total body fat
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- diet, Confounders controlled for: "medication use" 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.medication use
Alpha Diversity
- Pielou Quantifies how equal the community is numerically
- decreased
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Chao1 Abundance-based estimator of species richness
- decreased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- decreased
- Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
- decreased
- Richness Number of species
- decreased
- Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
- decreased
Signature 1
Needs review
Source: Gut microbiome
Description: Increased Prevotella, a genus associated with carbohydrate-rich diets, in individuals with lower Healthy Eating Index (HEI) scores, indicative of poor diet quality.
Abundance in Group 1: increased abundance in High Plasma LBP group
| NCBI | Quality Control | Links |
|---|---|---|
| Prevotellaceae | ||
| Dialister | ||
| Parabacteroides |
Revision editor(s): Vandana Maddi
Signature 2
Needs review
Source: Gut microbiome
Description: Decreased Bacteroides, a genus associated with fiber-rich diets, in individuals with lower HEI scores, reflecting poorer diet quality.
Abundance in Group 1: decreased abundance in High Plasma LBP group
| NCBI | Quality Control | Links |
|---|---|---|
| Faecalibacterium prausnitzii | ||
| Clostridium | ||
| Bacteroides |
Revision editor(s): Vandana Maddi
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