Targeted Analysis of the Gut Microbiome for Diagnosis, Prognosis and Treatment Individualization in Pediatric Inflammatory Bowel Disease

From BugSigDB
Reviewed Marked as Reviewed by Peace Sandy on 2024-2-13
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Olbjørn C, Småstuen MC, Moen AEF
Journal
Microorganisms
Year
2022
Keywords:
IBD, biologic therapy, biomarker, microbiota, pediatric, prognosis
We explored the fecal microbiota in pediatric patients <18 years of age with treatment-naïve IBD (80 Crohn’s disease (CD), 27 ulcerative colitis (UC)), in 50 non-IBD patients with gastrointestinal symptoms without inflammation and in 75 healthy children. Using a targeted qPCR approach, the quantities of more than 100 different bacterial species were measured. Results: The bacterial abundance was statistically significantly reduced in the IBD and non-IBD patients compared to the healthy children for several beneficial species. The CD patients had a lower abundance of Bifidobacterium species compared to the UC patients, and the IBD patients in need of biologic therapy had a lower abundance of butyrate producing bacteria. Based on the abundance of bacterial species at diagnosis, we constructed Diagnostic, Phenotype and Prognostic Indexes. Patients with a high Diagnostic Index had 2.5 times higher odds for having IBD than those with a lower index. The CD patients had a higher Phenotype Index than the UC patients. Patients with a high Prognostic Index had 2.1 higher odds for needing biologic therapy compared to those with a lower index. Conclusions: The fecal abundance of bacterial species can aid in diagnosing IBD, in distinguishing CD from UC and in identifying children with IBD in need of biologic therapy.

Experiment 1


Reviewed Marked as Reviewed by Chloe on 2023-12-14

Curated date: 2023/12/10

Curator: Yjung24

Revision editor(s): Yjung24, Peace Sandy

Subjects

Location of subjects
Norway
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
Inflammatory bowel disease autoimmune bowel disorder,Bowel Diseases, Inflammatory,IBD,INFLAMM BOWEL DIS,inflammatory bowel disease,Inflammatory Bowel Diseases,Inflammatory bowel disease
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy controls
Group 1 name Corresponds to the case (exposed) group for case-control studies
Inflammatory bowel disease patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients under 18 years old diagnosed with inflammatory bowel disease (Crohn's Disease or ulcerative colitis) from the catchment areas of two university hospitals in three population-based prospective epidemiological studies of treatment-naïve pediatric IBD in South-Eastern Norway between 2005-2015.
Group 0 sample size Number of subjects in the control (unexposed) group
75
Group 1 sample size Number of subjects in the case (exposed) group
107
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
Six Months

Lab analysis

Sequencing type
PCR
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
RT-qPCR

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances
Statistical test
Mann-Whitney (Wilcoxon)
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)?
No


Signature 1

Reviewed Marked as Reviewed by Chloe on 2023-12-14

Curated date: 2023/12/10

Curator: Yjung24

Revision editor(s): Yjung24

Source: Table 2

Description: Bacterial species exhibiting deviating abundances between patient and control groups. IBD vs Healthy.

Abundance in Group 1: decreased abundance in Inflammatory bowel disease patients

NCBI Quality ControlLinks
Bifidobacterium angulatum
Bifidobacterium bifidum
Bifidobacterium catenulatum
Bifidobacterium longum
Bifidobacterium pseudocatenulatum
Christensenella minuta
[Clostridium] leptum
[Clostridium] scindens
Lachnospira eligens
Agathobacter rectalis
Eubacterium ventriosum
Lactobacillus acidophilus
Lacticaseibacillus paracasei
Methanobrevibacter smithii
Paraprevotella clara
Roseburia intestinalis
Roseburia inulinivorans
Roseburia hominis
Ruminococcus bromii
Streptococcus sanguinis
Streptococcus thermophilus
Alistipes finegoldii
Alistipes shahii
Alistipes onderdonkii
Anaerostipes hadrus
Bacteroides caccae
Phocaeicola dorei
Barnesiella intestinihominis
Intestinibacter bartlettii
Akkermansia muciniphila

Revision editor(s): Yjung24

Experiment 2


Reviewed Marked as Reviewed by Chloe on 2023-12-14

Curated date: 2023/12/10

Curator: Yjung24

Revision editor(s): Yjung24, Peace Sandy

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy children
Group 1 name Corresponds to the case (exposed) group for case-control studies
Non-inflammatory bowel disease symptomatic controls
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
patients under 18 years presented with symptoms of inflammatory bowel disease (Crohn's Disease or ulcerative colitis) but did not meet the criteria for IBD and who had a macroscopically and histologically normal mucosa and normal MRI examination from the catchment areas of two university hospitals in three population-based prospective epidemiological studies of treatment-naïve pediatric IBD in South-Eastern Norway between 2005-2015.
Group 1 sample size Number of subjects in the case (exposed) group
50
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
antibiotics use within the last six months of study for healthy controls (group 0)

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Chloe on 2023-12-14

Curated date: 2023/12/10

Curator: Yjung24

Revision editor(s): Yjung24

Source: Table 2

Description: Bacterial species exhibiting deviating abundances between patient and control groups. Non-IBD vs. Healthy.

Abundance in Group 1: decreased abundance in Non-inflammatory bowel disease symptomatic controls

NCBI Quality ControlLinks
Bifidobacterium angulatum
Coprococcus comes
Lachnospira eligens
[Eubacterium] siraeum
Ruminococcus bromii
Streptococcus thermophilus
Alistipes shahii
Bacteroides caccae
Phocaeicola dorei

Revision editor(s): Yjung24

Signature 2

Reviewed Marked as Reviewed by Chloe on 2023-12-14

Curated date: 2023/12/10

Curator: Yjung24

Revision editor(s): Yjung24

Source: Table 2

Description: Bacterial species exhibiting deviating abundances between patient and control groups. Non-IBD vs. Healthy.

Abundance in Group 1: increased abundance in Non-inflammatory bowel disease symptomatic controls

NCBI Quality ControlLinks
Enterococcus faecium
Citrobacter koseri

Revision editor(s): Yjung24

Experiment 3


Reviewed Marked as Reviewed by Chloe on 2023-12-14

Curated date: 2023/12/10

Curator: Yjung24

Revision editor(s): Yjung24

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
non-inflammatory bowel disease symptomatic controls
Group 1 name Corresponds to the case (exposed) group for case-control studies
inflammatory bowel disease patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
patients under 18 diagnosed with inflammatory bowel disease (Crohn's Disease or ulcerative colitis) from the catchment areas of two university hospitals in three population-based prospective epidemiological studies of treatment-naïve pediatric IBD in South-Eastern Norway between 2005-2015.
Group 0 sample size Number of subjects in the control (unexposed) group
50
Group 1 sample size Number of subjects in the case (exposed) group
110

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Chloe on 2023-12-14

Curated date: 2023/12/10

Curator: Yjung24

Revision editor(s): Yjung24

Source: Table 2

Description: Bacterial species exhibiting deviating abundances between patient and control groups.

Abundance in Group 1: decreased abundance in inflammatory bowel disease patients

NCBI Quality ControlLinks
Paraprevotella clara
Bifidobacterium adolescentis
Bifidobacterium angulatum
Bifidobacterium bifidum
Christensenella minuta
[Clostridium] leptum
Desulfovibrio piger
Agathobacter rectalis
[Eubacterium] siraeum
Eubacterium ventriosum
Lactobacillus acidophilus
Lacticaseibacillus paracasei
Roseburia intestinalis
Roseburia inulinivorans
Roseburia hominis
Ruminococcus bromii
Alistipes finegoldii
Phocaeicola plebeius
Bacteroides stercoris
Akkermansia muciniphila

Revision editor(s): Yjung24

Signature 2

Reviewed Marked as Reviewed by Chloe on 2023-12-14

Curated date: 2023/12/10

Curator: Yjung24

Revision editor(s): Yjung24

Source: Table 2

Description: Bacterial species exhibiting deviating abundances between patient and control groups. IBD vs. Non-IBD.

Abundance in Group 1: increased abundance in inflammatory bowel disease patients

NCBI Quality ControlLinks
Haemophilus parainfluenzae

Revision editor(s): Yjung24

Experiment 4


Reviewed Marked as Reviewed by Chloe on 2023-12-14

Curated date: 2023/12/10

Curator: Yjung24

Revision editor(s): Yjung24

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Phenotype Phenotype,phenotype
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Crohn's Disease patients with inflammatory phenotypes
Group 1 name Corresponds to the case (exposed) group for case-control studies
Crohn's Disease patients with stricturing and/or penetrating phenotypes
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
patients under 18 diagnosed with Crohn's Disease with stricturing and/or penetrating phenotypes
Group 0 sample size Number of subjects in the control (unexposed) group
53
Group 1 sample size Number of subjects in the case (exposed) group
27
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
Not specified

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Chloe on 2023-12-14

Curated date: 2023/12/10

Curator: Yjung24

Revision editor(s): Yjung24

Source: Section 3.4 (text)

Description: The CD patients had a significantly lower abundance for five bacterial species and a higher abundance for five bacterial species. The CD patients with stricturing and/or penetrating phenotypes had a lower abundance of four species and a higher abundance of Escherichia coli (p = 0.010) compared to the CD patients with an inflammatory phenotype.

Abundance in Group 1: decreased abundance in Crohn's Disease patients with stricturing and/or penetrating phenotypes

NCBI Quality ControlLinks
Christensenella minuta
[Clostridium] scindens
Lachnospira eligens
Roseburia hominis

Revision editor(s): Yjung24

Signature 2

Reviewed Marked as Reviewed by Chloe on 2023-12-14

Curated date: 2023/12/10

Curator: Yjung24

Revision editor(s): Yjung24

Source: Section 3.4 (text)

Description: The CD patients had a significantly lower abundance for five bacterial species and a higher abundance for five bacterial species. The CD patients with stricturing and/or penetrating phenotypes had a lower abundance of four species and a higher abundance of Escherichia coli (p = 0.010) compared to the CD patients with an inflammatory phenotype.

Abundance in Group 1: increased abundance in Crohn's Disease patients with stricturing and/or penetrating phenotypes

NCBI Quality ControlLinks
Escherichia coli

Revision editor(s): Yjung24

Experiment 5


Reviewed Marked as Reviewed by Chloe on 2023-12-14

Curated date: 2023/12/10

Curator: Yjung24

Revision editor(s): Yjung24

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Treatment Treatment,treatment
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Inflammatory bowel disease patients treated with conventional therapy
Group 1 name Corresponds to the case (exposed) group for case-control studies
Inflammatory bowel disease patients treated with biological therapy
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
58% of inflammatory bowel disease patients were later treated with biologic therapy due to failure to induce remission with conventional treatments or relapse after primary induction.
Group 0 sample size Number of subjects in the control (unexposed) group
46
Group 1 sample size Number of subjects in the case (exposed) group
64

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Chloe on 2023-12-14

Curated date: 2023/12/10

Curator: Yjung24

Revision editor(s): Yjung24

Source: Table 3

Description: Bacterial species exhibiting deviating abundances between medical therapy groups and between groups with high and low calprotectin levels.

Abundance in Group 1: decreased abundance in Inflammatory bowel disease patients treated with biological therapy

NCBI Quality ControlLinks
Bifidobacterium adolescentis
Bifidobacterium bifidum
Agathobacter rectalis
Roseburia hominis
Roseburia inulinivorans
Ruminococcus bromii
Bacteroides finegoldii
Bacteroides intestinalis
Bacteroides cellulosilyticus
Paraprevotella clara

Revision editor(s): Yjung24

Signature 2

Reviewed Marked as Reviewed by Chloe on 2023-12-14

Curated date: 2023/12/10

Curator: Yjung24

Revision editor(s): Yjung24

Source: Table 3

Description: Bacterial species exhibiting deviating abundances between medical therapy groups and between groups with high and low calprotectin levels.

Abundance in Group 1: increased abundance in Inflammatory bowel disease patients treated with biological therapy

NCBI Quality ControlLinks
Mediterraneibacter gnavus
Phocaeicola vulgatus

Revision editor(s): Yjung24

Experiment 6


Reviewed Marked as Reviewed by Chloe on 2023-12-14

Curated date: 2023/12/10

Curator: Yjung24

Revision editor(s): Yjung24

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Increased inflammatory response Increased inflammatory response,increased inflammatory response
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Inflammatory bowel disease patients with fecal calprotectin levels < 1000 mg/kg
Group 1 name Corresponds to the case (exposed) group for case-control studies
Inflammatory bowel disease patients with fecal calprotectin levels > 1000 mg/kg
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Inflammatory bowel disease patients with higher fecal protectin levels (31 with CD and 12 with UC had above 1000 mg/kg).
Group 0 sample size Number of subjects in the control (unexposed) group
67
Group 1 sample size Number of subjects in the case (exposed) group
43

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Chloe on 2023-12-14

Curated date: 2023/12/10

Curator: Yjung24

Revision editor(s): Yjung24

Source: Table 3

Description: Bacterial species exhibiting deviating abundances between medical therapy groups and between groups with high and low calprotectin levels.

Abundance in Group 1: decreased abundance in Inflammatory bowel disease patients with fecal calprotectin levels > 1000 mg/kg

NCBI Quality ControlLinks
Roseburia hominis
Roseburia inulinivorans
Roseburia intestinalis
Alistipes finegoldii
Barnesiella intestinihominis

Revision editor(s): Yjung24

Experiment 7


Needs review

Curated date: 2024/01/21

Curator: Yjung24

Revision editor(s): Yjung24

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Inflammatory bowel disease patients receiving one biologic or conventional therapy
Group 1 name Corresponds to the case (exposed) group for case-control studies
Inflammatory bowel disease patients receiving second class of biologic drug
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
A subset of the IBD patients receiving biologic therapy needed further treatment escalation to a second class of biologics.
Group 0 sample size Number of subjects in the control (unexposed) group
88
Group 1 sample size Number of subjects in the case (exposed) group
22
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
antibiotics use within the last six months of study for healthy controls (group 0)

Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2024/01/21

Curator: Yjung24

Revision editor(s): Yjung24

Source: Text: Page 6 Paragraph 2

Description: A subset of the IBD patients receiving biologic therapy needed further treatment escalation to a second class of biologics. These patients had a significantly lower abundance of Bifidobacterium bifidum, Roseburia hominis and Bacteroides xylanisolvens compared to the IBD patients who received one biologic or conventional therapy.

Abundance in Group 1: decreased abundance in Inflammatory bowel disease patients receiving second class of biologic drug

NCBI Quality ControlLinks
Bifidobacterium bifidum
Roseburia hominis
Bacteroides xylanisolvens

Revision editor(s): Yjung24