Widespread protein lysine acetylation in gut microbiome and its alterations in patients with Crohn's disease

From BugSigDB
Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-5
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
Authors
Zhang X, Ning Z, Mayne J, Yang Y, Deeke SA, Walker K, Farnsworth CL, Stokes MP, Couture JF, Mack D, Stintzi A, Figeys D
Journal
Nature communications
Year
2020
Lysine acetylation (Kac), an abundant post-translational modification (PTM) in prokaryotes, regulates various microbial metabolic pathways. However, no studies have examined protein Kac at the microbiome level, and it remains unknown whether Kac level is altered in patient microbiomes. Herein, we use a peptide immuno-affinity enrichment strategy coupled with mass spectrometry to characterize protein Kac in the microbiome, which successfully identifies 35,200 Kac peptides from microbial or human proteins in gut microbiome samples. We demonstrate that Kac is widely distributed in gut microbial metabolic pathways, including anaerobic fermentation to generate short-chain fatty acids. Applying to the analyses of microbiomes of patients with Crohn's disease identifies 52 host and 136 microbial protein Kac sites that are differentially abundant in disease versus controls. This microbiome-wide acetylomic approach aids in advancing functional microbiome research.

Experiment 1


Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-5

Curated date: 2023/03/11

Curator: Sophy

Revision editor(s): Sophy, Folakunmi

Subjects

Location of subjects
Canada
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 , Mucosa of descending colon 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,Descending colon mucosa,Descending colon mucosa of organ,Descending colon mucous membrane,Descending colon organ mucosa,Mucosa of organ of descending colon,Mucous membrane of descending colon,Organ mucosa of descending colon,Mucosa of descending colon
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Crohn's disease Colitis, Granulomatous,CROHN DIS,Crohn Disease,Crohn disease,Crohn's associated gastritis,Crohn's disease,Crohn's disease of colon,Crohn's disease of large bowel,CROHNS DIS,Crohns Disease,Enteritis, Granulomatous,Enteritis, Regional,Gastritis Associated with Crohn Disease,Gastritis Associated with Crohn's Disease,granulomatous colitis,Ileitis, Regional,Ileitis, Terminal,Ileocolitis,pediatric Crohn's disease,regional enteritis,crohn disease
Group 0 name Corresponds to the control (unexposed) group for case-control studies
healthy adults
Group 1 name Corresponds to the case (exposed) group for case-control studies
pediatric crohn's disease
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
children (<18 years old) diagnosed with crohn’s disease. The exclusion criteria implemented to further refine the cohort in this study include: presence of diabetes mellitus, presence of infectious gastroenteritis within the past 2 months, and irritable bowel syndrome.
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
10
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
4 weeks including probiotics use

Lab analysis

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
Mass spectrometry

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances
Statistical test
LEfSe
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
2


Signature 1

Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-5

Curated date: 2023/03/11

Curator: Sophy

Revision editor(s): Sophy, Chloe

Source: Figure 5a

Description: Taxonomic alterations of protein acetylation in the pediatric CD microbiome. LEfSe analysis of lysine acetylome-based taxonomic compositions.

Abundance in Group 1: decreased abundance in pediatric crohn's disease

NCBI Quality ControlLinks
Megamonas
Megamonas funiformis
Roseburia inulinivorans
Selenomonadaceae
Selenomonadales
[Eubacterium] eligens ATCC 27750

Revision editor(s): Sophy, Chloe

Signature 2

Reviewed Marked as Reviewed by Chloe on 2023-3-20

Curated date: 2023/03/11

Curator: Sophy

Revision editor(s): Sophy

Source: Figure 5a

Description: Taxonomic alterations of protein acetylation in the pediatric CD microbiome. acetylome-based. LEfSe analysis of lysine acetylome-based taxonomic compositions.

Abundance in Group 1: increased abundance in pediatric crohn's disease

NCBI Quality ControlLinks
Bacilli

Revision editor(s): Sophy

Experiment 2


Needs review

Curated date: 2023/11/23

Curator: Folakunmi

Revision editor(s): Folakunmi

Differences from previous experiment shown

Subjects

Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2023/11/23

Curator: Folakunmi

Revision editor(s): Folakunmi

Source: figure 5b

Description: Taxonomic alterations of protein acetylation in the pediatric CD microbiome. LEfSe analysis of metaproteome-based taxonomic compositions.

Abundance in Group 1: increased abundance in pediatric crohn's disease

NCBI Quality ControlLinks
Gammaproteobacteria
Fungi
Spirochaetia
Saccharomycetes
Saccharomycetales
Viruses
Spirochaeta
Ascomycota
Anaerotruncus
Caudoviricetes

Revision editor(s): Folakunmi

Signature 2

Needs review

Curated date: 2023/11/23

Curator: Folakunmi

Revision editor(s): Folakunmi

Source: figure 5b

Description: Taxonomic alterations of protein acetylation in the pediatric CD microbiome. LEfSe analysis of metaproteome-based taxonomic compositions.

Abundance in Group 1: decreased abundance in pediatric crohn's disease

NCBI Quality ControlLinks
Bacteroides uniformis
Dorea
Prevotella micans
Streptococcus
Thomasclavelia spiroformis
Blautia hansenii
Streptococcaceae
Bacilli
Roseburia faecis
Lactobacillales
Roseburia intestinalis
Thomasclavelia

Revision editor(s): Folakunmi

Experiment 3


Needs review

Curated date: 2023/11/23

Curator: Folakunmi

Revision editor(s): Folakunmi

Differences from previous experiment shown

Subjects

Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2023/11/23

Curator: Folakunmi

Revision editor(s): Folakunmi

Source: figure 5e

Description: Taxonomic alterations of protein acetylation in the pediatric CD microbiome. LEfSe analysis of the acetylome-to-metaproteome ratios of all quantified taxa in the lysine acetylome data set.

Abundance in Group 1: increased abundance in pediatric crohn's disease

NCBI Quality ControlLinks
Bacilli
Ruminococcus

Revision editor(s): Folakunmi

Experiment 4


Needs review

Curated date: 2023/11/24

Curator: Folakunmi

Revision editor(s): Folakunmi

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
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
gut microbiome measurement gut microbiome measurement
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Metaproteome
Group 1 name Corresponds to the case (exposed) group for case-control studies
Lysine acetylome
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
relative abundance of kac levels (for each taxon listed in supplementary data 3) in human fecal microbiome samples lysine acetylome
Group 0 sample size Number of subjects in the control (unexposed) group
209
Group 1 sample size Number of subjects in the case (exposed) group
209

Lab analysis

Statistical Analysis

Statistical test
Mann-Whitney (Wilcoxon)
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
Not specified


Signature 1

Needs review

Curated date: 2023/11/24

Curator: Folakunmi

Revision editor(s): Folakunmi

Source: figure 2b

Description: Lysine acetylome-to-metaproteome ratios of quantified phyla and genera in human gut microbiome. Comparisons of the percentage of acetylation in lysine acetylomic aliquot with that in metaproteomic aliquot.

Abundance in Group 1: increased abundance in Lysine acetylome

NCBI Quality ControlLinks
Fusicatenibacter
Odoribacter
Lachnoclostridium
Butyricicoccus
Bacillota

Revision editor(s): Folakunmi

Signature 2

Needs review

Curated date: 2023/11/24

Curator: Folakunmi

Revision editor(s): Folakunmi

Source: figure 2b

Description: Lysine acetylome-to-metaproteome ratios of quantified phyla and genera in human gut microbiome. Comparisons of the percentage of acetylation in lysine acetylomic aliquot with that in metaproteomic aliquot.

Abundance in Group 1: decreased abundance in Lysine acetylome

NCBI Quality ControlLinks
Bacteroides
Butyrivibrio
Actinomycetota
Pseudomonadota
Parasutterella
Collinsella
Chordata
Gemmiger
Homo

Revision editor(s): Folakunmi