Changes in the Gut Microbiome Associated with Intussusception in Patients with Peutz-Jeghers Syndrome

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Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Wang Z, Liang L, Liu L, Wang Z, Wang Y, Yu Z, Wu B, Chen Y
Journal
Microbiology spectrum
Year
2023
Keywords:
Peutz-Jeghers syndrome, biomarkers, functional analysis, gut microbiota, intussusception
Peutz-Jeghers syndrome (PJS) is a rare hereditary disorder characterized by intestinal polyposis, and intestinal intussusception is one of the most urgent complications. While it is known that imbalance of the gut microbiota is highly associated with intestinal disorders, the role of the gut microbiome in the pathogenesis of PJS has not been reported. In this study, we performed 16S rRNA sequencing on stools from 168 patients and 68 healthy family members who lived together to determine the gut microbiome composition of PJS patients. Metagenomics sequencing was further performed on the representative samples (61 PJS patients and 27 healthy family members) to analyze the functional changes. We found that the fecal microbiome of patients with PJS showed a greater variation in β-diversity. An enhancement of Escherichia coli and a reduction of Faecalibacterium prausnitzii was identified in PJS patients. Further reduction of Faecalibacterium prausnitzii was the characteristic microbial change observed in patients with intussusception. Functional analysis revealed that the abundance of propanoate metabolism was enriched in PJS patients and further enriched in those with intussusception. Escherichia coli was the major contributor to the enrichment of this metabolism pathway, which was associated with the abnormal expression of methylglyoxal synthase (encoded by mgsA) and phosphate acetyltransferase (encoded by pta). Our findings showed a distinct gut microbiome signature in PJS patients and identified the connection between the gut microbiome and intussusception. Alterations in the gut microbiome might be involved in the pathogenesis of PJS and may serve as biomarkers for gastrointestinal surveillance. IMPORTANCE Recent research has established a link between the gut microbiome and polyps and neoplasia, and antibiotic use influences the microbiome and the development of colorectal polyps. Familial adenomatous polyposis (FAP), which is characterized by the early development of benign precursor lesions (polyps), is associated with enterotoxigenic Bacteroides fragilis and Escherichia coli biofilms. However, the relationship between the gut microbiome and the pathophysiology of PJS has not yet been established. In this study, we found that PJS patients had a distinct microbiome composition, with a greater variation in β-diversity, an increase in Escherichia coli, and a decrease in Faecalibacterium prausnitzii. A further reduction of Faecalibacterium prausnitzii was observed in patients with intussusception. Moreover, PJS involved increased propanoate metabolism as well as abnormal mgsA and pta expression. These findings may contribute to a better understanding of the etiology of PJS and improve disease control strategies.

Experiment 1


Needs review

Curated date: 2024/03/19

Curator: Rahila

Revision editor(s): Rahila

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
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
Peutz-Jeghers Polyp Peutz Jeghers polyp,Peutz-Jeghers polyp,Peutz-Jeghers Polyp,peutz-Jeghers Polyp
Group 0 name Corresponds to the control (unexposed) group for case-control studies
healthy control (family members)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Peutz-Jeghers syndrome (PJS)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients who has Peutz-Jeghers syndrome (PJS)
Group 0 sample size Number of subjects in the control (unexposed) group
68
Group 1 sample size Number of subjects in the case (exposed) group
168
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
within 3 months

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V3-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).
relative abundances
Statistical test
LEfSe
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
3.0

Alpha Diversity

Simpson Estimator of species richness and species evenness: more weight on species evenness
unchanged

Signature 1

Needs review

Curated date: 2024/03/19

Curator: Rahila

Revision editor(s): Rahila

Source: FIG 1 (F)

Description: LEfSe analysis identified the differentially abundant taxa between PJS patients and healthy controls (LDA > 3.0).

Abundance in Group 1: increased abundance in Peutz-Jeghers syndrome (PJS)

NCBI Quality ControlLinks
Pseudomonadota
Gammaproteobacteria
Enterobacterales
Escherichia/Shigella sp.
Enterobacteriaceae
Klebsiella
Fusobacteriaceae
Fusobacteriia
Fusobacteriales
Fusobacterium
Veillonella
Akkermansiaceae
Verrucomicrobiae
Verrucomicrobiales
Akkermansia
Verrucomicrobiota

Revision editor(s): Rahila

Experiment 2


Needs review

Curated date: 2024/03/19

Curator: Rahila

Revision editor(s): Rahila

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Without Intussusception (NI-PJS)
Group 1 name Corresponds to the case (exposed) group for case-control studies
With Intussusception (I-PJS)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients who had undergone at least one intussusception (I-PJS)
Group 0 sample size Number of subjects in the control (unexposed) group
57
Group 1 sample size Number of subjects in the case (exposed) group
106

Lab analysis

Statistical Analysis

Alpha Diversity

Simpson Estimator of species richness and species evenness: more weight on species evenness
unchanged

Signature 1

Needs review

Curated date: 2024/03/19

Curator: Rahila

Revision editor(s): Rahila

Source: FIG 2 (D)

Description: LEfSe analysis identified the differences in abundance between I-PJS and NI-PJS patients (LDA > 3.0).

Abundance in Group 1: decreased abundance in With Intussusception (I-PJS)

NCBI Quality ControlLinks
Actinomycetota
Bifidobacteriaceae
Bifidobacteriales
Bifidobacterium
Burkholderiaceae
Faecalibacterium
Peptostreptococcaceae
Romboutsia
Lachnospiraceae UCG_004Lachnospiraceae UCG_004
BetaproteobacterialesBetaproteobacteriales

Revision editor(s): Rahila

Signature 2

Needs review

Curated date: 2024/03/19

Curator: Rahila

Revision editor(s): Rahila

Source: FIG 2 (D)

Description: LEfSe analysis identified the differences in abundance between I-PJS and NI-PJS patients (LDA > 3.0).

Abundance in Group 1: increased abundance in With Intussusception (I-PJS)

NCBI Quality ControlLinks
Blautia
Enterobacterales
Enterobacteriaceae
Escherichia/Shigella sp.
Fusobacteriaceae
Fusobacteriales
Fusobacteriia
Fusobacterium
Gammaproteobacteria
Klebsiella
Pseudomonadota

Revision editor(s): Rahila

Experiment 3


Needs review

Curated date: 2024/03/19

Curator: Rahila

Revision editor(s): Rahila

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
healthy control (family members)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Peutz-Jeghers syndrome (PJS)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients who has Peutz-Jeghers syndrome (PJS)
Group 0 sample size Number of subjects in the control (unexposed) group
27
Group 1 sample size Number of subjects in the case (exposed) group
61

Lab analysis

Sequencing type
WMS
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
Not specified

Statistical Analysis

Statistical test
LEfSe
Mann-Whitney (Wilcoxon)
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
2.0


Signature 1

Needs review

Curated date: 2024/03/19

Curator: Rahila

Revision editor(s): Rahila

Source: FIG 3 (D)

Description: LEfSe analysis identified the differential species between PJS patients and healthy controls (LDA > 2.0).

Abundance in Group 1: increased abundance in Peutz-Jeghers syndrome (PJS)

NCBI Quality ControlLinks
Acinetobacter baumannii
Escherichia coli
Klebsiella pneumoniae
Klebsiella quasipneumoniae
Klebsiella variicola
Leyella stercorea
Leyella stercorea CAG:629
Salmonella enterica
Shigella boydii
Shigella dysenteriae
Shigella flexneri
Shigella sonnei
unclassified Bacteria
unclassified Enterobacter
unclassified Enterobacteriaceae
unclassified Escherichia
unclassified Gammaproteobacteria
unclassified Klebsiella
unclassified Pseudomonadota
unclassified Enterobacterales
Plesiomonas shigelloides

Revision editor(s): Rahila

Experiment 4


Needs review

Curated date: 2024/03/19

Curator: Rahila

Revision editor(s): Rahila

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Without Intussusception (NI-PJS)
Group 1 name Corresponds to the case (exposed) group for case-control studies
With Intussusception (I-PJS)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients who had undergone at least one intussusception (I-PJS)
Group 0 sample size Number of subjects in the control (unexposed) group
26
Group 1 sample size Number of subjects in the case (exposed) group
35

Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2024/03/19

Curator: Rahila

Revision editor(s): Rahila

Source: FIG 4 (D)

Description: LEfSe analysis showed the differential species between I-PJS and NI-PJS patients (LDA > 2.0).

Abundance in Group 1: increased abundance in With Intussusception (I-PJS)

NCBI Quality ControlLinks
Aeromonas veronii
Collinsella sp. AF08-23
Dialister invisus CAG:218
Fusobacterium necrogenes
Fusobacterium sp.
unclassified Aeromonas
bacterium 1xD8-27

Revision editor(s): Rahila

Signature 2

Needs review

Curated date: 2024/03/19

Curator: Rahila

Revision editor(s): Rahila

Source: FIG 4 (D)

Description: LEfSe analysis showed the differential species between I-PJS and NI-PJS patients (LDA > 2.0).

Abundance in Group 1: decreased abundance in With Intussusception (I-PJS)

NCBI Quality ControlLinks
Faecalibacterium prausnitzii
unclassified Faecalibacterium
Faecalibacterium sp.
Faecalibacterium sp. CAG:74_58_120
Prevotella sp. AM42-24
Alistipes senegalensis
unclassified Flavobacteriaceae
Coprobacter fastidiosus
Faecalibacterium sp. AF10-46
Haemophilus parainfluenzae

Revision editor(s): Rahila