CoChat
Sign Up
Cited by 1,371Gut microbiota and healthOral microbiology and periodontitis researchNutritional Studies and Diet

The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.

Symptomatic atherosclerosis is associated with an altered gut metagenome

Open access
Karlsson, Fredrik H., Fåk, Frida, Nookaew, Intawat, Tremaroli, Valentina, Fagerberg, Björn, Petranovic, Dina, Bäckhed, Fredrik, Nielsen, Jens·2012·Nature Communications
DOI 10.1038/ncomms2266PMC PMC3538954
Open this paper in CoChat — free accountOpen PDF

Abstract

Recent findings have implicated the gut microbiota as a contributor of metabolic diseases through the modulation of host metabolism and inflammation. Atherosclerosis is associated with lipid accumulation and inflammation in the arterial wall, and bacteria have been suggested as a causative agent of this disease. Here we use shotgun sequencing of the gut metagenome to demonstrate that the genus Collinsella was enriched in patients with symptomatic atherosclerosis, defined as stenotic atherosclerotic plaques in the carotid artery leading to cerebrovascular events, whereas Roseburia and Eubacterium were enriched in healthy controls. Further characterization of the functional capacity of the metagenomes revealed that patient gut metagenomes were enriched in genes encoding peptidoglycan synthesis and depleted in phytoene dehydrogenase; patients also had reduced serum levels of β-carotene. Our findings suggest that the gut metagenome is associated with the inflammatory status of the host and patients with symptomatic atherosclerosis harbor characteristic changes in the gut metagenome. The gut microbiota has emerged as an environmental factor that can influence the development of obesity and diabetes. Here, Karlsson et al. report compositional and functional alterations of the gut metagenome in patients with symptomatic atherosclerosis.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/ncomms2266

Cites

48 of 48 references verified0 citation errors · 0 not checkable

Statistics

Figures

Figure 1 Microbial composition associated with symptomatic atherosclerosis. (a) Illustration of our bioinformatics pipeline for analysing metagenome data to elucidate its relation to human metabolic disease. Sequence reads from the gut metagenome were generated with high-throughput sequencing technology and subjected to quality control. High-quality reads were used for alignment to reference genomes to estimate species abundance. De novo assembly of the metagenome allows for discovery of new genes not yet found in databases. Annotation of genes to KEGG allows for integration of information at the gene level with the metabolic network. Data on plasma metabolites and proteins together with gut metagenomic data constitute a basis for discovery of mechanisms for gut metagenome association with etiology of complex diseases. (b) Principal component analysis of microbial species abundance using health status as instrumental variable. Red is patients (P, n=12), green controls (C, n=13). The relation between microbial abundance and health status was assessed with Monte Carlo simulations with 10,000 replications by which a P-value was calculated. (c) Abundance of bacterial genera and species that differ between patients (n=12) with symptomatic atherosclerosis (P) and controls (n=13) (C). Adj. P<0.05 for all. (d) Bacterial genera correlating with biomarkers of atherosclerosis, using Spearman’s correlation. All samples, including the two excluded controls (see methods for details), were used for correlations with triglycerides, CRP (n=27, respectively) and white blood cell count (WBC; n=23). Only controls were used for low-density lipoprotein (LDL), high-density lipoprotein (HDL) and cholesterol correlations to avoid interactions with possible drug effects (n=15). *Adj. P<0.05, **adj. P<0.01 and ***adj. P<0.001. Boxes denote the interquartile range (IQR) between the first and third quartiles and the line within denotes the median; whiskers denote the lowest and highest values within 1.5 times IQR from the first and third quartiles, respectively. Circles denote data points beyond the whiskers.
Figure 1 Microbial composition associated with symptomatic atherosclerosis. (a) Illustration of our bioinformatics pipeline for analysing metagenome data to elucidate its relation to human metabolic disease. Sequence reads from the gut metagenome were generated with high-throughput sequencing technology and subjected to quality control. High-quality reads were used for alignment to reference genomes to estimate species abundance. De novo assembly of the metagenome allows for discovery of new genes not yet found in databases. Annotation of genes to KEGG allows for integration of information at the gene level with the metabolic network. Data on plasma metabolites and proteins together with gut metagenomic data constitute a basis for discovery of mechanisms for gut metagenome association with etiology of complex diseases. (b) Principal component analysis of microbial species abundance using health status as instrumental variable. Red is patients (P, n=12), green controls (C, n=13). The relation between microbial abundance and health status was assessed with Monte Carlo simulations with 10,000 replications by which a P-value was calculated. (c) Abundance of bacterial genera and species that differ between patients (n=12) with symptomatic atherosclerosis (P) and controls (n=13) (C). Adj. P<0.05 for all. (d) Bacterial genera correlating with biomarkers of atherosclerosis, using Spearman’s correlation. All samples, including the two excluded controls (see methods for details), were used for correlations with triglycerides, CRP (n=27, respectively) and white blood cell count (WBC; n=23). Only controls were used for low-density lipoprotein (LDL), high-density lipoprotein (HDL) and cholesterol correlations to avoid interactions with possible drug effects (n=15). *Adj. P<0.05, **adj. P<0.01 and ***adj. P<0.001. Boxes denote the interquartile range (IQR) between the first and third quartiles and the line within denotes the median; whiskers denote the lowest and highest values within 1.5 times IQR from the first and third quartiles, respectively. Circles denote data points beyond the whiskers.CC BY-NC-ND · PubMed Central
Figure 2 Symptomatic atherosclerosis correlates with gut enterotypes. (a) Three enterotypes in our cohort based on the abundance of genera. Controls and patients are denoted by filled triangles and empty triangles, respectively. Two subjects not included in the comparison are represented by empty circles. Green is enterotype 1, red is enterotype 2 and blue is enterotype 3. (b) Abundance of Bacteroides, Prevotella and Ruminococcus, proposed drivers of the three enterotypes. Boxes denote the interquartile range (IQR) between the first and third quartiles and the line within denotes the median; whiskers denote the lowest and highest values within 1.5 times IQR from the first and third quartiles, respectively. Circles denote data points beyond the whiskers.
Figure 2 Symptomatic atherosclerosis correlates with gut enterotypes. (a) Three enterotypes in our cohort based on the abundance of genera. Controls and patients are denoted by filled triangles and empty triangles, respectively. Two subjects not included in the comparison are represented by empty circles. Green is enterotype 1, red is enterotype 2 and blue is enterotype 3. (b) Abundance of Bacteroides, Prevotella and Ruminococcus, proposed drivers of the three enterotypes. Boxes denote the interquartile range (IQR) between the first and third quartiles and the line within denotes the median; whiskers denote the lowest and highest values within 1.5 times IQR from the first and third quartiles, respectively. Circles denote data points beyond the whiskers.CC BY-NC-ND · PubMed Central
Figure 3 KOs are associated with symptomatic atherosclerosis. (a) Peptidoglycan KOs were enriched in patients and eight out of nine KOs correlated positively with white blood cell levels. (b) β-Oxidation KOs correlate with plasma triglyceride levels. (c) The glutamine synthetase—glutamine oxoglutarate aminotransferase system (K00265, K00266 and K01915) with high affinity for ammonium is enriched in patients. In all panels, red indicates enriched in patients (P), green indicates enriched in controls (C). *Adj. P<0.05, **adj. P<0.01 and ***adj. P<0.001. All samples were used for correlations with triglycerides, CRP (n=27, respectively) and white blood cell count (WBC; n=23). Only controls were used for low-density lipoprotein (LDL), high-density lipoprotein (HDL) and cholesterol correlations to avoid interactions with possible drug effects (n=15). Adj., adjusted.
Figure 3 KOs are associated with symptomatic atherosclerosis. (a) Peptidoglycan KOs were enriched in patients and eight out of nine KOs correlated positively with white blood cell levels. (b) β-Oxidation KOs correlate with plasma triglyceride levels. (c) The glutamine synthetase—glutamine oxoglutarate aminotransferase system (K00265, K00266 and K01915) with high affinity for ammonium is enriched in patients. In all panels, red indicates enriched in patients (P), green indicates enriched in controls (C). *Adj. P<0.05, **adj. P<0.01 and ***adj. P<0.001. All samples were used for correlations with triglycerides, CRP (n=27, respectively) and white blood cell count (WBC; n=23). Only controls were used for low-density lipoprotein (LDL), high-density lipoprotein (HDL) and cholesterol correlations to avoid interactions with possible drug effects (n=15). Adj., adjusted.CC BY-NC-ND · PubMed Central
Figure 4 Phytoene dehydrogenase K10027 is enriched in the gut metagenome of healthy controls. β-Carotene (P=0.05, Student’s t-test) but not lycopene (P=0.35, Student’s t-test) was enriched in serum of healthy controls. Red is patients (P), green controls (C). Boxes denote the interquartile range (IQR) between the first and third quartiles and the line within denotes the median; whiskers denote the lowest and highest values within 1.5 times IQR from the first and third quartiles, respectively. Circles denote data points beyond the whiskers.
Figure 4 Phytoene dehydrogenase K10027 is enriched in the gut metagenome of healthy controls. β-Carotene (P=0.05, Student’s t-test) but not lycopene (P=0.35, Student’s t-test) was enriched in serum of healthy controls. Red is patients (P), green controls (C). Boxes denote the interquartile range (IQR) between the first and third quartiles and the line within denotes the median; whiskers denote the lowest and highest values within 1.5 times IQR from the first and third quartiles, respectively. Circles denote data points beyond the whiskers.CC BY-NC-ND · PubMed Central

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 48 references

Cited by

Sorted by citations

Related

See all

Metadata

Authors
Karlsson, F. H., Fåk, F., Nookaew, I., Tremaroli, V., Fagerberg, B., Petranovic, D., Bäckhed, F., & Nielsen, J.
Affiliations
  • Chalmers University of Technology (SE)
  • University of Gothenburg (SE)
Corresponding author
  • Bäckhed, Fredrik
  • Nielsen, Jens
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2012-12-04
Volume
3
Issue
1
Pages
1245-1245
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/ncomms2266
PMC
PMC3538954
OpenAlex
W2163940893
Semantic Scholar
fa78fbe4819f11f57f8abcdc9460b2aceded402d
Cited by
1,371
References
48
Citations by year
2026: 83 · 2025: 138 · 2024: 139 · 2023: 137 · 2022: 160 · 2021: 143 · 2020: 126 · 2019: 98 · 2018: 97 · 2017: 73 · 2016: 51 · 2015: 59 · 2014: 37 · 2013: 29
FWCI
16.08
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • Lund University Publications (Lund University) (submittedVersion)
  • Chalmers Publication Library (Chalmers University of Technology) (submittedVersion)
  • Chalmers Research (Chalmers University of Technology) (submittedVersion)
Funders
  • Stiftelsen för Strategisk Forskning
  • Knut och Alice Wallenbergs Stiftelse
  • Vetenskapsrådet
  • Sahlgrenska Universitetssjukhuset
  • Göteborgs Universitet
  • Fondation Chalmers
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
Keywords
gut microbiota, gut metagenome, Collinsella, Roseburia, Eubacterium, carotid artery stenosis, cerebrovascular disease, peptidoglycan biosynthesis, phytoene desaturase, beta-carotene, inflammation, lipid accumulation
MeSH terms
Aged, Eubacterium, Female, Humans, Inflammation, Male, Oxidoreductases, Peptidoglycan, Case-Control Studies, beta Carotene, Actinobacteria, Gastrointestinal Tract, Atherosclerosis, Metagenome

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review