Cannabis sativa L. alleviates loperamide-induced constipation by modulating the composition of gut microbiota in mice

Study information

Needs review

study design

laboratory experiment

Citation

PMID PubMed identifier for scientific articles.

36532754

DOI Digital object identifier for electronic documents.

10.3389/fphar.2022.1033069

URI

Authors

Li R, Li M, Li B, Chen WH, Liu Z

Journal

Frontiers in pharmacology

Year

2022

Keywords:

Butyricicoccus, Cannabis sativa L., Parasutterella, constipation, gut microbiota

MaZiRenWan (MZRW) is the most frequently used Traditional Chinese Medicine formula to treat chronic constipation, Cannabis sativa L. is regarded as a monarch drug in MZRW. However, the targets of Cannabis sativa L. that enhance colonic motility and improve constipation symptoms remain unknown. This study was designed to investigate the laxative effect and underlying mechanism of the water extract of Cannabis sativa L. (WECSL) using a loperamide-induced constipation mouse model. We found that WECSL treatment significantly improved intestinal motility and water-electrolyte metabolism, decreased inflammatory responses, prevented gut barrier damage, and relieved anxiety and depression in constipated mice. WECSL also structurally remodeled the composition of the gut microbiota and altered the abundance of bacteria related to inflammation, specifically Butyricicoccus and Parasutterella. Moreover, WECSL failed to relieve constipation symptoms following intestinal flora depletion, indicating that WECSL alleviates constipation symptoms depending on the gut microbiota. Our research provides a basis for WECSL to be further investigated in the treatment of constipation from the perspective of modern medicine.

Experiment 1

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Curated date: 2025/04/07

Curator: Tosin

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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: Traditional Chinese medicine type TCM type,Traditional Chinese medicine type,traditional Chinese medicine type

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Combination of Con (blank) and Lop + WECSL (Loperamide hydrochloride-induced constipation model + water extract of Cannabis sativa L.)

Group 1 name Corresponds to the case (exposed) group for case-control studies: Lop (Loperamide hydrochloride-induced constipation model)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Mice injected with loperamide (10.0 mg/kg) twice a day for 2 weeks

Group 0 sample size Number of subjects in the control (unexposed) group: 16

Group 1 sample size Number of subjects in the case (exposed) group: 8

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: 3

Signature 1

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Curated date: 2025/04/07

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Source: Figure 6A and 6B

Description: Identification of most characteristic taxa among experimental groups by linear discriminant analysis (LDA) effect size (LEfSe).

Abundance in Group 1: increased abundance in Lop (Loperamide hydrochloride-induced constipation model)

NCBI	Quality Control	Links
Parabacteroides
Parasutterella
Blautia
TuzzerellaTuzzerella
Gordonibacter
Clostridium
[Eubacterium] brachy

Revision editor(s): Tosin

Experiment 2

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Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Combination of Con (blank) and Lop (Loperamide hydrochloride-induced constipation model)

Group 1 name Corresponds to the case (exposed) group for case-control studies: Lop + WESCL (Loperamide hydrochloride-induced constipation model + water extract of Cannabis sativa L. )

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Constipation mice pretreated with the water extract of Cannabis sativa L. (WECSL)

Statistical Analysis

Signature 1

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Curated date: 2025/04/07

Curator: Tosin

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Source: Figure 6A and 6B

Description: Identification of most characteristic taxa among experimental groups by linear discriminant analysis (LDA) effect size (LEfSe).

Abundance in Group 1: increased abundance in Lop + WESCL (Loperamide hydrochloride-induced constipation model + water extract of Cannabis sativa L. )

NCBI	Quality Control	Links
Allobaculum
Anaerotruncus
Butyricicoccus
Monoglobus
Muribaculum
Paraprevotella
Prevotella
Tyzzerella
Termite treponema clusterTermite treponema cluster

Revision editor(s): Tosin

Experiment 3

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Curated date: 2025/04/07

Curator: Tosin

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Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Combination of Lop (Loperamide hydrochloride-induced constipation model) and Lop +WESCL (Loperamide hydrochloride-induced constipation model + water extract of Cannabis sativa L.)

Group 1 name Corresponds to the case (exposed) group for case-control studies: Con (blank)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Mice in the Con group were injected with the same volume of saline

Statistical Analysis

Signature 1

Edit History Delete

Mark reviewed

Your review change was submitted

Needs review

Curated date: 2025/04/07

Curator: Tosin

Revision editor(s): Tosin

Source: Figure 6A and 6B

Description: Identification of most characteristic taxa among experimental groups by linear discriminant analysis (LDA) effect size (LEfSe).

Abundance in Group 1: increased abundance in Con (blank)

NCBI	Quality Control	Links
Alistipes
Anaeroplasma
Bacteroides
Bilophila
Candidatus Saccharimonas
Intestinimonas
Lachnoclostridium
Muribaculaceae
Clostridia vadinBB60 groupClostridia vadinBB60 group
Lachnospiraceae UCG 004Lachnospiraceae UCG 004
Lachnospiraceae ASF356Lachnospiraceae ASF356
Oscillospirales UCG 010Oscillospirales UCG 010

Revision editor(s): Tosin