Gastrointestinal Dysmotility Predisposes to Colitis through Regulation of Gut Microbial Composition and Linoleic Acid Metabolism

From BugSigDB
Reviewed Marked as Reviewed by Svetlana up on 2025-4-24
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Zhang Y, Song F, Yang M, Chen C, Cui J, Xing M, Dai Y, Li M, Cao Y, Lu L, Zhu H, Liu Y, Ma C, Wei Q, Qin H, Li J
Journal
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
Year
2024
Keywords:
gut microbiota, gut motility, immune cell, inflammatory bowel disease, linoleic acid
Disrupted gastrointestinal (GI) motility is highly prevalent in patients with inflammatory bowel disease (IBD), but its potential causative role remains unknown. Herein, the role and the mechanism of impaired GI motility in colitis pathogenesis are investigated. Increased colonic mucosal inflammation is found in patients with chronic constipation (CC). Mice with GI dysmotility induced by genetic mutation or chemical insult exhibit increased susceptibility to colitis, dependent on the gut microbiota. GI dysmotility markedly decreases the abundance of Lactobacillus animlalis and increases the abundance of Akkermansia muciniphila. The reduction in L. animlalis, leads to the accumulation of linoleic acid due to compromised conversion to conjugated linoleic acid. The accumulation of linoleic acid inhibits Treg cell differentiation and increases colitis susceptibility via inducing macrophage infiltration and proinflammatory cytokine expression in macrophage. Lactobacillus and A. muciniphila abnormalities are also observed in CC and IBD patients, and mice receiving fecal microbiota from CC patients displayed an increased susceptibility to colitis. These findings suggest that GI dysmotility predisposes host to colitis development by modulating the composition of microbiota and facilitating linoleic acid accumulation. Targeted modulation of microbiota and linoleic acid metabolism may be promising to protect patients with motility disorder from intestinal inflammation.

Experiment 1


Reviewed Marked as Reviewed by Svetlana up on 2025-4-24

Curated date: 2025/04/14

Curator: MyleeeA

Revision editor(s): MyleeeA

Subjects

Location of subjects
China
Host species Species from which microbiome was sampled. Contact us to have more species added.
Mus musculus
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
Colitis Colitides,colitis,colitis (disease),colon inflammation,inflammation of colon,Colitis
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Wild Type (WT) Mice
Group 1 name Corresponds to the case (exposed) group for case-control studies
Kit wsh/wsh mice
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
c-Kit receptor dysfunction-based ICC-deficient murine model (Kitwsh/wsh) before Dextran Sulfate Sodium (DSS) treatment. Kitwsh/wsh C57BL/6J mice were from Jackson Laboratory (BarHarbor, ME).
Group 0 sample size Number of subjects in the control (unexposed) group
6
Group 1 sample size Number of subjects in the case (exposed) group
6

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)?
No
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
2.5
Matched on Factors on which subjects have been matched on in a case-control study
age, sex

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Chao1 Abundance-based estimator of species richness
increased

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2025-4-24

Curated date: 2025/04/14

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 3C

Description: Differences in microbial taxa at species levels between Wild Type (WT) and Kit wsh/wsh mice were calculated by LDA effect size (LEfSe).

Abundance in Group 1: increased abundance in Kit wsh/wsh mice

NCBI Quality ControlLinks
Akkermansia muciniphila
Lachnospiraceae bacterium MD335
Helicobacter ganmani
Bacteroides acidifaciens
Lactobacillus intestinalis
Phocaeicola sartorii
Helicobacter hepaticus
Clostridiales bacterium CIEAF 020
Ruminococcus sp. 5_1_39BFAA
bacterium mpn-isolate group 9

Revision editor(s): MyleeeA

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2025-4-24

Curated date: 2025/04/14

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 3C

Description: Differences in microbial taxa at species levels between Wild Type (WT) and Kit wsh/wsh mice were calculated by LDA effect size (LEfSe).

Abundance in Group 1: decreased abundance in Kit wsh/wsh mice

NCBI Quality ControlLinks
Clostridium sp. Culture-54
Ligilactobacillus animalis
Mucispirillum schaedleri
Parabacteroides goldsteinii
Adlercreutzia mucosicola
Lachnospiraceae bacterium A4

Revision editor(s): MyleeeA

Experiment 2


Reviewed Marked as Reviewed by Svetlana up on 2025-4-24

Curated date: 2025/04/14

Curator: MyleeeA

Revision editor(s): MyleeeA

Differences from previous experiment shown

Subjects

Lab analysis

Statistical Analysis

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

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Chao1 Abundance-based estimator of species richness
increased

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2025-4-24

Curated date: 2025/04/14

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 3D

Description: Differences in microbial taxa at the genus and species levels between Wild Type (WT) and Kit wsh/wsh mice.

Abundance in Group 1: increased abundance in Kit wsh/wsh mice

NCBI Quality ControlLinks
Akkermansia
Akkermansia muciniphila

Revision editor(s): MyleeeA

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2025-4-24

Curated date: 2025/04/14

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 3D

Description: Differences in microbial taxa at the genus and species levels between Wild Type (WT) and Kit wsh/wsh mice.

Abundance in Group 1: decreased abundance in Kit wsh/wsh mice

NCBI Quality ControlLinks
Lactobacillus
Ligilactobacillus animalis
Lactobacillus johnsonii

Revision editor(s): MyleeeA

Experiment 3


Reviewed Marked as Reviewed by Svetlana up on 2025-4-24

Curated date: 2025/04/14

Curator: MyleeeA

Revision editor(s): MyleeeA

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Wild Type (WT) Mice (No DSS)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Kit wsh/wsh mice (No DSS)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
c-Kit receptor dysfunction-based ICC-deficient murine model (Kitwsh/wsh) without Dextran Sulfate Sodium (DSS) treatment. Kitwsh/wsh C57BL/6J mice were from Jackson Laboratory (BarHarbor, ME).

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Chao1 Abundance-based estimator of species richness
increased

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2025-4-24

Curated date: 2025/04/14

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 3E

Description: Differences in microbial taxa at the species levels between Wild Type (WT) and Kit wsh/wsh mice not treated with DSS.

Abundance in Group 1: increased abundance in Kit wsh/wsh mice (No DSS)

NCBI Quality ControlLinks
Akkermansia muciniphila

Revision editor(s): MyleeeA

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2025-4-24

Curated date: 2025/04/14

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 3E

Description: Differences in microbial taxa at the species levels between Wild Type (WT) and Kit wsh/wsh mice not treated with DSS.

Abundance in Group 1: decreased abundance in Kit wsh/wsh mice (No DSS)

NCBI Quality ControlLinks
Lactobacillus johnsonii
Ligilactobacillus animalis

Revision editor(s): MyleeeA

Experiment 4


Reviewed Marked as Reviewed by Svetlana up on 2025-4-24

Curated date: 2025/04/14

Curator: MyleeeA

Revision editor(s): MyleeeA

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Response to transplant Response to transplant,response to transplant
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy controls - Fecal Microbiota Transplantation (HC-FMT)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Chronic Constipation - Fecal Microbiota Transplantation (CC-FMT)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Fecal microbiota transplant (FMT), recipient mice were pre-treated with a cocktail of antibiotics (ABX) in drinking water for 2 weeks. Mice were administered filtered donor fecal homogenate by oral gavage (300 μl per mouse) one day after ABX treatment every other day over a period of 10 days.

Lab analysis

Statistical Analysis

Matched on Factors on which subjects have been matched on in a case-control study
Not specified


Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2025-4-24

Curated date: 2025/04/15

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 8F

Description: Differences in microbial taxa significant between Chronic Constipation - Fecal Microbiota Transplantation (CC-FMT) and Healthy controls - Fecal Microbiota Transplantation (HC-FMT).

Abundance in Group 1: increased abundance in Chronic Constipation - Fecal Microbiota Transplantation (CC-FMT)

NCBI Quality ControlLinks
Akkermansia muciniphila

Revision editor(s): MyleeeA

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2025-4-24

Curated date: 2025/04/15

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 8F

Description: Differences in microbial taxa significant between Chronic Constipation - Fecal Microbiota Transplantation (CC-FMT) and Healthy controls - Fecal Microbiota Transplantation (HC-FMT).

Abundance in Group 1: decreased abundance in Chronic Constipation - Fecal Microbiota Transplantation (CC-FMT)

NCBI Quality ControlLinks
Lactobacillus

Revision editor(s): MyleeeA

Experiment 5


Reviewed Marked as Reviewed by Svetlana up on 2025-4-24

Curated date: 2025/04/14

Curator: MyleeeA

Revision editor(s): MyleeeA

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
Wild Type (WT) Mice (DSS)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Kit wsh/wsh mice (DSS)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
c-Kit receptor dysfunction-based ICC-deficient murine model (Kitwsh/wsh) with Dextran Sulfate Sodium (DSS) treatment. Kitwsh/wsh C57BL/6J mice were from Jackson Laboratory (BarHarbor, ME).

Lab analysis

Statistical Analysis

Matched on Factors on which subjects have been matched on in a case-control study
age, sex

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Chao1 Abundance-based estimator of species richness
increased

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2025-4-24

Curated date: 2025/04/15

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 3E

Description: Differences in microbial taxa at the species levels between Wild Type (WT) and Kit wsh/wsh mice treated with DSS.

Abundance in Group 1: increased abundance in Kit wsh/wsh mice (DSS)

NCBI Quality ControlLinks
Akkermansia muciniphila

Revision editor(s): MyleeeA

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2025-4-24

Curated date: 2025/04/15

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 3E

Description: Differences in microbial taxa at the species levels between Wild Type (WT) and Kit wsh/wsh mice treated with DSS.

Abundance in Group 1: decreased abundance in Kit wsh/wsh mice (DSS)

NCBI Quality ControlLinks
Ligilactobacillus animalis
Lactobacillus johnsonii

Revision editor(s): MyleeeA

Experiment 6


Reviewed Marked as Reviewed by Svetlana up on 2025-4-24

Curated date: 2025/04/14

Curator: MyleeeA

Revision editor(s): MyleeeA

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Diet measurement Diet measurement,diet measurement
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Control Diet (CD) mice
Group 1 name Corresponds to the case (exposed) group for case-control studies
Low-carbohydrate and high-protein diet (LCHD) mice
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
WT mice fed with an isocaloric low-carbohydrate and high-protein diet (LCHD, 28.9% carbohydrate, 60.0% protein, and 11.1% fat as percentages of calories) for 4 weeks
Group 0 sample size Number of subjects in the control (unexposed) group
Not specified
Group 1 sample size Number of subjects in the case (exposed) group
Not specified

Lab analysis

Statistical Analysis

Matched on Factors on which subjects have been matched on in a case-control study
Not specified


Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2025-4-24

Curated date: 2025/04/15

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Supplementary Figure 4C

Description: Differences in microbial taxa significant between mice fed with Low-carbohydrate and high-protein diet (LCHD) and Control Diet (CD).

Abundance in Group 1: increased abundance in Low-carbohydrate and high-protein diet (LCHD) mice

NCBI Quality ControlLinks
Akkermansia muciniphila

Revision editor(s): MyleeeA

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2025-4-24

Curated date: 2025/04/15

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Supplementary Figure 4C

Description: Differences in microbial taxa significant between mice fed with Low-carbohydrate and high-protein diet (LCHD) and Control Diet (CD).

Abundance in Group 1: decreased abundance in Low-carbohydrate and high-protein diet (LCHD) mice

NCBI Quality ControlLinks
Lactobacillus

Revision editor(s): MyleeeA

Experiment 7


Reviewed Marked as Reviewed by Svetlana up on 2025-4-24

Curated date: 2025/04/14

Curator: MyleeeA

Revision editor(s): MyleeeA

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Colitis Colitides,colitis,colitis (disease),colon inflammation,inflammation of colon,Colitis
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Wild Type (WT) Mice
Group 1 name Corresponds to the case (exposed) group for case-control studies
Kit wsh/wsh Mice
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
c-Kit receptor dysfunction-based ICC-deficient murine model (Kitwsh/wsh). Kitwsh/wsh C57BL/6J mice were from Jackson Laboratory (BarHarbor, ME).
Group 0 sample size Number of subjects in the control (unexposed) group
6
Group 1 sample size Number of subjects in the case (exposed) group
6

Lab analysis

Statistical Analysis

Statistical test
ANOVA
Matched on Factors on which subjects have been matched on in a case-control study
age, sex

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Chao1 Abundance-based estimator of species richness
increased

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2025-4-24

Curated date: 2025/04/15

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Supplementary Figure 5A

Description: Differences in microbial taxa at the species levels between Wild Type (WT) and Kit wsh/wsh mice.

Abundance in Group 1: increased abundance in Kit wsh/wsh Mice

NCBI Quality ControlLinks
Akkermansia muciniphila

Revision editor(s): MyleeeA

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2025-4-24

Curated date: 2025/04/15

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Supplementary Figure 5A

Description: Differences in microbial taxa at the species levels between Wild Type (WT) and Kit wsh/wsh mice.

Abundance in Group 1: decreased abundance in Kit wsh/wsh Mice

NCBI Quality ControlLinks
Ligilactobacillus animalis
Lactobacillus johnsonii

Revision editor(s): MyleeeA

Experiment 8


Reviewed Marked as Reviewed by Svetlana up on 2025-4-24

Curated date: 2025/04/14

Curator: MyleeeA

Revision editor(s): MyleeeA

Differences from previous experiment shown

Subjects

Host species Species from which microbiome was sampled. Contact us to have more species added.
Homo sapiens
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Chronic constipation Chronic constipation,Infrequent bowel movements,chronic constipation
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy controls (HC)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Chronic Constipation (CC)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with Chronic Constipation
Group 0 sample size Number of subjects in the control (unexposed) group
30
Group 1 sample size Number of subjects in the case (exposed) group
30
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
2 months

Lab analysis

Statistical Analysis

Matched on Factors on which subjects have been matched on in a case-control study
Not specified


Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2025-4-24

Curated date: 2025/04/15

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 8C

Description: Relative abundance of microbial taxa in stool samples from Chronic constipation patients (CC) and Healthy controls (HC).

Abundance in Group 1: increased abundance in Chronic Constipation (CC)

NCBI Quality ControlLinks
Akkermansia muciniphila

Revision editor(s): MyleeeA

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2025-4-24

Curated date: 2025/04/15

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 8C

Description: Relative abundance of microbial taxa in stool samples from Chronic constipation patients (CC) and Healthy controls (HC).

Abundance in Group 1: decreased abundance in Chronic Constipation (CC)

NCBI Quality ControlLinks
Lactobacillus

Revision editor(s): MyleeeA

Experiment 9


Reviewed Marked as Reviewed by Svetlana up on 2025-4-24

Curated date: 2025/04/14

Curator: MyleeeA

Revision editor(s): MyleeeA

Differences from previous experiment shown

Subjects

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 1 name Corresponds to the case (exposed) group for case-control studies
Crohn's Disease (CD)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with Crohn's disease
Group 1 sample size Number of subjects in the case (exposed) group
32

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2025-4-24

Curated date: 2025/04/15

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 8C

Description: Relative abundance of microbial taxa in stool samples from Crohn's Disease patients (CD) and Healthy controls (HC).

Abundance in Group 1: decreased abundance in Crohn's Disease (CD)

NCBI Quality ControlLinks
Lactobacillus

Revision editor(s): MyleeeA

Experiment 10


Reviewed Marked as Reviewed by Svetlana up on 2025-4-24

Curated date: 2025/04/14

Curator: MyleeeA

Revision editor(s): MyleeeA

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Ulcerative colitis colitis ulcerative,Colitis, Ulcerative,Left-sided ulcerative (chronic) colitis,Left-sided ulcerative colitis,left-sided ulcerative colitis,Other ulcerative colitis,Other ulcerative colitis (disorder),UC - ulcerative colitis,ulcerative colitis,ulcerative colitis (disease),ulcerative colitis (disorder),Ulcerative colitis, unspecified,ULCERATVE COLITIS UNSPCF,Ulcerative colitis
Group 1 name Corresponds to the case (exposed) group for case-control studies
Ulcerative colitis
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with Ulcerative colitis
Group 1 sample size Number of subjects in the case (exposed) group
25

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2025-4-24

Curated date: 2025/04/15

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 8C

Description: Relative abundance of microbial taxa in stool samples from Ulcerative colitis patients (UC) and Healthy controls (HC).

Abundance in Group 1: decreased abundance in Ulcerative colitis

NCBI Quality ControlLinks
Lactobacillus

Revision editor(s): MyleeeA