The treatment-naive microbiome in new-onset Crohn's disease

From BugSigDB
Reviewed Marked as Reviewed by Claregrieve1 on 2023-4-22
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
Authors
Gevers D, Kugathasan S, Denson LA, Vázquez-Baeza Y, Van Treuren W, Ren B, Schwager E, Knights D, Song SJ, Yassour M, Morgan XC, Kostic AD, Luo C, González A, McDonald D, Haberman Y, Walters T, Baker S, Rosh J, Stephens M, Heyman M, Markowitz J, Baldassano R, Griffiths A, Sylvester F, Mack D, Kim S, Crandall W, Hyams J, Huttenhower C, Knight R, Xavier RJ
Journal
Cell host & microbe
Year
2014
Inflammatory bowel diseases (IBDs), including Crohn's disease (CD), are genetically linked to host pathways that implicate an underlying role for aberrant immune responses to intestinal microbiota. However, patterns of gut microbiome dysbiosis in IBD patients are inconsistent among published studies. Using samples from multiple gastrointestinal locations collected prior to treatment in new-onset cases, we studied the microbiome in the largest pediatric CD cohort to date. An axis defined by an increased abundance in bacteria which include Enterobacteriaceae, Pasteurellacaea, Veillonellaceae, and Fusobacteriaceae, and decreased abundance in Erysipelotrichales, Bacteroidales, and Clostridiales, correlates strongly with disease status. Microbiome comparison between CD patients with and without antibiotic exposure indicates that antibiotic use amplifies the microbial dysbiosis associated with CD. Comparing the microbial signatures between the ileum, the rectum, and fecal samples indicates that at this early stage of disease, assessing the rectal mucosal-associated microbiome offers unique potential for convenient and early diagnosis of CD.

Experiment 1


Reviewed Marked as Reviewed by Atrayees on 2023-6-16

Curated date: 2023/03/13

Curator: Khadeeejah

Revision editor(s): Chloe, Claregrieve1, Khadeeejah, Atrayees, Aiyshaaaa, Victoria

Subjects

Location of subjects
China
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
Ileum , Rectum Distal intestine,Intestinum ileum,Lower intestine,Posterior intestine,Ileum,ileum,Intestinum rectum,Rectal sac,Terminal portion of intestine,Terminal portion of large intestine,Rectum,rectum
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,crohn's disease
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy control
Group 1 name Corresponds to the case (exposed) group for case-control studies
Crohn's disease
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Treatment-naive pediatric patients (ages 3-17) with new-onset Crohn's disease
Group 0 sample size Number of subjects in the control (unexposed) group
221
Group 1 sample size Number of subjects in the case (exposed) group
447

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
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
Linear Regression
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, antibiotic exposure, race, sex, Confounders controlled for: "subject" 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.subject, Confounders controlled for: "diagnosis" 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.diagnosis, Confounders controlled for: "ulcering" 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.ulcering, Confounders controlled for: "PCDAI" 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.PCDAI, Confounders controlled for: "biopsy location" 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.biopsy location, Confounders controlled for: "ileal involvement" 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.ileal involvement

Alpha Diversity

Richness Number of species
decreased

Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-6-16

Curated date: 2023/03/13

Curator: Khadeeejah

Revision editor(s): Khadeeejah, Atrayees, Chloe, Aiyshaaaa

Source: Table S2A

Description: Alteration in the abundance of several taxa in the ileal and rectal samples, in the diagnosis variable.

Abundance in Group 1: increased abundance in Crohn's disease

NCBI Quality ControlLinks
Micrococcaceae
Campylobacterales
Neisseria
Veillonella parvula
Actinobacillus
Aggregatibacter
Aggregatibacter segnis
Neisseriaceae
Veillonella dispar
Fusobacteriales
Fusobacteriaceae
Burkholderiaceae
Veillonellaceae
Betaproteobacteria
Haemophilus
Haemophilus parainfluenzae
Pasteurellaceae
Enterobacteriaceae

Revision editor(s): Khadeeejah, Atrayees, Chloe, Aiyshaaaa

Signature 2

Reviewed Marked as Reviewed by Atrayees on 2023-6-16

Curated date: 2023/03/13

Curator: Khadeeejah

Revision editor(s): Khadeeejah, Aiyshaaaa, Chloe, Atrayees

Source: Table S2A

Description: Alteration in the abundance of several taxa in the ileal and rectal samples, in the diagnosis variable.

Abundance in Group 1: decreased abundance in Crohn's disease

NCBI Quality ControlLinks
Bacillota
Clostridia
Eubacteriales
Lachnospiraceae
Faecalibacterium
Faecalibacterium prausnitzii
Erysipelotrichaceae
Parabacteroides
Porphyromonadaceae
Roseburia
Coprococcus
Blautia
Clostridiaceae
Ruminococcus
Bacteroides uniformis
Eubacterium
Bifidobacterium
Amedibacillus dolichus
Bifidobacteriaceae
Actinomycetota
Holdemanella biformis
Clostridium
Bifidobacterium adolescentis
Coprococcus catus
Verrucomicrobiaceae
Roseburia faecis
Christensenellaceae
Ruminococcus bromii
Akkermansia muciniphila

Revision editor(s): Khadeeejah, Aiyshaaaa, Chloe, Atrayees

Experiment 2


Reviewed Marked as Reviewed by Atrayees on 2023-6-16

Curated date: 2023/04/04

Curator: Khadeeejah

Revision editor(s): Khadeeejah, Aiyshaaaa, Atrayees, Victoria

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


Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, antibiotic exposure, race, sex, Confounders controlled for: "ulcering" 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.ulcering, Confounders controlled for: "subject" 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.subject, Confounders controlled for: "diagnosis" 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.diagnosis, Confounders controlled for: "PCDAI" 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.PCDAI, Confounders controlled for: "biopsy location" 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.biopsy location, Confounders controlled for: "ileal involvement" 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.ileal involvement


Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-6-16

Curated date: 2023/04/04

Curator: Khadeeejah

Revision editor(s): Khadeeejah, Aiyshaaaa, Atrayees

Source: Table S2B

Description: Taxa in stool samples significantly associated with disease.

Abundance in Group 1: increased abundance in Crohn's disease

NCBI Quality ControlLinks
Lachnospiraceae
Ruminococcus
Dorea
Blautia producta
[Ruminococcus] torques

Revision editor(s): Khadeeejah, Aiyshaaaa, Atrayees

Experiment 3


Reviewed Marked as Reviewed by Atrayees on 2023-6-16

Curated date: 2023/04/04

Curator: Khadeeejah

Revision editor(s): Khadeeejah, Aiyshaaaa, Atrayees, Victoria

Differences from previous experiment shown

Subjects

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Ileum , Rectum , Feces Distal intestine,Intestinum ileum,Lower intestine,Posterior intestine,Ileum,ileum,Intestinum rectum,Rectal sac,Terminal portion of intestine,Terminal portion of large intestine,Rectum,rectum,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


Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, antibiotic exposure, race, sex, Confounders controlled for: "PCDAI" 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.PCDAI, Confounders controlled for: "diagnosis" 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.diagnosis, Confounders controlled for: "subject" 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.subject, Confounders controlled for: "ileal involvement" 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.ileal involvement, Confounders controlled for: "ulcering" 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.ulcering, Confounders controlled for: "biopsy location" 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.biopsy location


Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-6-16

Curated date: 2023/04/04

Curator: Khadeeejah

Revision editor(s): Khadeeejah, Aiyshaaaa, Atrayees

Source: Table S2C

Description: precise differences between the mucosal tissue and stool samples within patients with new-onset CD

Abundance in Group 1: increased abundance in Crohn's disease

NCBI Quality ControlLinks
Lactobacillaceae
Eubacteriaceae
Streptococcus anginosus
Lactobacillus
Blautia producta
Amedibacillus dolichus
Eubacterium
Ruminococcus
Mediterraneibacter gnavus
Clostridium
Bacilli
Eggerthella
Dorea
Clostridiaceae
Streptococcus
Oscillospiraceae
Lactobacillales
Streptococcaceae
Coriobacteriaceae
Actinomycetota
Erysipelotrichaceae
Coprococcus
Bifidobacterium
Bifidobacteriaceae
Blautia
Lachnospiraceae
Bacillota
Eubacteriales

Revision editor(s): Khadeeejah, Aiyshaaaa, Atrayees

Signature 2

Reviewed Marked as Reviewed by Atrayees on 2023-6-16

Curated date: 2023/04/04

Curator: Khadeeejah

Revision editor(s): Khadeeejah, Aiyshaaaa, Atrayees

Source: Tabls S2C

Description: precise differences between the mucosal tissue and stool samples within patients with new-onset CD

Abundance in Group 1: decreased abundance in Crohn's disease

NCBI Quality ControlLinks
Bacteroides
Pseudomonadota
Bacteroidales
Bacteroidia
Gammaproteobacteria
Betaproteobacteria
Bacteroides fragilis
Burkholderiales
Desulfovibrionaceae
Rhodocyclaceae
Sphingomonadales
Aggregatibacter
Pseudomonadales
Moraxellaceae
Acinetobacter
Fusobacteriales
Fusobacteriaceae
Staphylococcus
Neisseriaceae
Bacillales
Tissierellaceae
Neisseria
Weeksellaceae
Micrococcaceae
Rothia
Campylobacterales
Rothia mucilaginosa
Corynebacterium
Porphyromonas

Revision editor(s): Khadeeejah, Aiyshaaaa, Atrayees