Rifaximin Ameliorates Loperamide-Induced Constipation in Rats through the Regulation of Gut Microbiota and Serum Metabolites

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Reviewed Marked as Reviewed by Svetlana up on 2025-4-10
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Luo M, Xie P, Deng X, Fan J, Xiong L
Journal
Nutrients
Year
2023
Keywords:
5-HT, bile acids, constipation, gut microbiota, loperamide, metabolites, rifaximin
Structural changes in the gut microbiota are closely related to the development of functional constipation, and regulating the gut microbiota can improve constipation. Rifaximin is a poorly absorbed antibiotic beneficial for regulating gut microbiota, but few studies have reported its effects on constipation. The purpose of this study was to investigate the effect of rifaximin on loperamide-induced constipation in SD rats. The results showed that rifaximin improved constipation by increasing serum 5-HT, SP, and the mRNA expression of AQP3, AQP8, and reducing the mRNA expression of TLR2 and TLR4. In addition, rifaximin could regulate the gut microbiota of constipated rats, such as increasing the potentially beneficial bacteria Akkermansia muciniphila and Lactobacillus murinus, reducing the Bifidobacterium pseudolongum. According to metabolomics analysis, many serum metabolites, including bile acids and steroids, were changed in constipated rats and were recovered via rifaximin intervention. In conclusion, rifaximin might improve loperamide-induced constipation in rats by increasing serum excitatory neurotransmitters and neuropeptides, modulating water metabolism, and facilitating intestinal inflammation. Muti-Omics analysis results showed that rifaximin has beneficial regulatory effects on the gut microbiota and serum metabolites in constipated rats, which might play critical roles in alleviating constipation. This study suggests that rifaximin might be a potential strategy for treating constipation.

Experiment 1


Reviewed Marked as Reviewed by Svetlana up on 2025-4-10

Curated date: 2025/04/02

Curator: Tosin

Revision editor(s): Tosin

Subjects

Location of subjects
China
Host species Species from which microbiome was sampled. Contact us to have more species added.
Rattus norvegicus
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
Response to antibiotic Response to antibiotic,response to antibiotic
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Combination of LOP (loperamide) and RIF (rifaximin) group
Group 1 name Corresponds to the case (exposed) group for case-control studies
CTR (control) group
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Rats in this group were injected with 0.9% saline.
Group 0 sample size Number of subjects in the control (unexposed) group
14
Group 1 sample size Number of subjects in the case (exposed) group
7

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
3.5


Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2025-4-10

Curated date: 2025/04/03

Curator: Tosin

Revision editor(s): Tosin

Source: Figure 3G and 3H

Description: Histogram of LDA value distribution generated by LEfSe indicating the differences of bacterial communities among three groups after LDA using a threshold score of LDA > 3.5

Abundance in Group 1: increased abundance in CTR (control) group

NCBI Quality ControlLinks
Candidatus Altimarinota
Candidatus Saccharimonadaceae
Candidatus Saccharimonadales
Candidatus Saccharimonadia
Candidatus Saccharimonas
Lactobacillus intestinalis
Ligilactobacillus murinus
Rikenellaceae
Clostridia UCG-014Clostridia UCG-014
Alistipes

Revision editor(s): Tosin

Experiment 2


Reviewed Marked as Reviewed by Svetlana up on 2025-4-10

Curated date: 2025/04/03

Curator: Tosin

Revision editor(s): Tosin

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Combination of CTR (control) and RIF (rifaximin) group
Group 1 name Corresponds to the case (exposed) group for case-control studies
LOP (loperamide) group
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Rats in this group were injected subcutaneously with 5 mg kg−1 of body weight loperamide in 0.9% saline solution twice daily at 09:00 am and 5:00 pm for 14 days

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2025-4-10

Curated date: 2025/04/03

Curator: Tosin

Revision editor(s): Tosin

Source: Figure 3G and 3H

Description: Histogram of LDA value distribution generated by LEfSe indicating the differences of bacterial communities among three groups after LDA using a threshold score of LDA > 3.5

Abundance in Group 1: increased abundance in LOP (loperamide) group

NCBI Quality ControlLinks
Acidimicrobiia
Actinomycetota
Allobaculum
Atopobiaceae
Bifidobacteriaceae
Bifidobacteriales
Bifidobacterium
Bifidobacterium pseudolongum
Clostridiaceae
Clostridium
Coriobacteriales
Coriobacteriia
Dubosiella
Erysipelotrichaceae
Erysipelotrichales
Eubacteriales
Faecalibaculum
Faecalibaculum rodentium
Turicibacter
uncultured Allobaculum sp.
Coriobacteriaceae UCG-002Coriobacteriaceae UCG-002
Clostridia UCG 014Clostridia UCG 014

Revision editor(s): Tosin

Experiment 3


Reviewed Marked as Reviewed by Svetlana up on 2025-4-10

Curated date: 2025/04/03

Curator: Tosin

Revision editor(s): Tosin

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Combination of CTR (control) and LOP (loperamide) group
Group 1 name Corresponds to the case (exposed) group for case-control studies
RIF (rifaximin) group
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
The rats in the RIF group were treated with rifaximin (75 mg kg−1 body weight) by gavage administration one hour after LOP was injected

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2025-4-10

Curated date: 2025/04/03

Curator: Tosin

Revision editor(s): Tosin

Source: Figure 3G and 3H

Description: Histogram of LDA value distribution generated by LEfSe indicating the differences of bacterial communities among three groups after LDA using a threshold score of LDA > 3.5

Abundance in Group 1: increased abundance in RIF (rifaximin) group

NCBI Quality ControlLinks
Akkermansia
Akkermansia muciniphila
Akkermansiaceae
Blautia
Ruminococcus gauvreauii
Verrucomicrobiales
Verrucomicrobiia
Verrucomicrobiota
unidentified rumen bacterium RF39

Revision editor(s): Tosin

Experiment 4


Reviewed Marked as Reviewed by Svetlana up on 2025-4-10

Curated date: 2025/04/03

Curator: Tosin

Revision editor(s): Tosin

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
CTR (control) group
Group 1 name Corresponds to the case (exposed) group for case-control studies
LOP (loperamide) group
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Rats in this group were injected subcutaneously with 5 mg kg−1 of body weight loperamide in 0.9% saline solution twice daily at 09:00 am and 5:00 pm for 14 days
Group 0 sample size Number of subjects in the control (unexposed) group
7

Lab analysis

Statistical Analysis

Statistical test
Kruskall-Wallis
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
unchanged
Chao1 Abundance-based estimator of species richness
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2025-4-10

Curated date: 2025/04/03

Curator: Tosin

Revision editor(s): Tosin

Source: Figure 4A, 4B and 4C

Description: Relative abundances of gut microbiota at the phylum, genus and species level among CTR (control) and LOP (loperamide) groups.

Abundance in Group 1: increased abundance in LOP (loperamide) group

NCBI Quality ControlLinks
Actinomycetota
Allobaculum
Bifidobacterium
Bifidobacterium pseudolongum
Clostridium
Dubosiella
Faecalibaculum
Faecalibaculum rodentium
Coriobacteriaceae UCG 002Coriobacteriaceae UCG 002

Revision editor(s): Tosin

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2025-4-10

Curated date: 2025/04/03

Curator: Tosin

Revision editor(s): Tosin

Source: Figure 4A, 4B and 4C

Description: Relative abundances of gut microbiota at the phylum, genus and species level among CTR (control) and LOP (loperamide) groups.

Abundance in Group 1: decreased abundance in LOP (loperamide) group

NCBI Quality ControlLinks
Ligilactobacillus murinus

Revision editor(s): Tosin

Experiment 5


Reviewed Marked as Reviewed by Svetlana up on 2025-4-10

Curated date: 2025/04/03

Curator: Tosin

Revision editor(s): Tosin

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
LOP (loperamide) group
Group 1 name Corresponds to the case (exposed) group for case-control studies
RIF (rifaximin) group
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
The rats in the RIF group were treated with rifaximin (75 mg kg−1 body weight) by gavage administration one hour after LOP was injected

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2025-4-10

Curated date: 2025/04/03

Curator: Tosin

Revision editor(s): Tosin

Source: Figure 4A, 4B, 4C, Table S1 and Table S2

Description: Relative abundances of gut microbiota at the phylum, genus and species level among LOP (loperamide) and RIF (rifaximin) groups

Abundance in Group 1: increased abundance in RIF (rifaximin) group

NCBI Quality ControlLinks
Akkermansia
Akkermansia muciniphila
Anaerofustis
Anaerofustis stercorihominis DSM 17244
Blautia
Bradyrhizobium
Bradyrhizobium elkanii
Coprobacillaceae
Enterorhabdus
Faecalitalea
Globicatella
Gordonibacter
Lachnoclostridium
Lachnospiraceae bacterium MD335
Lactobacillus
Ligilactobacillus murinus
Phocaeicola paurosaccharolyticus
Plesiomonas
Plesiomonas shigelloides
Rothia
Ruminococcus
Ruminococcus gauvreauii
Thomasclavelia
Verrucomicrobiota
[Clostridium] innocuum
Erysipelotrichaceae UCG-003Erysipelotrichaceae UCG-003
A2A2
Defluviitaleaceae UCG 011Defluviitaleaceae UCG 011
Erysipelotrichaceae
Eubacterium ruminantium
[Eubacterium] nodatum

Revision editor(s): Tosin

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2025-4-10

Curated date: 2025/04/03

Curator: Tosin

Revision editor(s): Tosin

Source: Figure 4A, 4B, 4C, Table S1 and Table S2

Description: Relative abundances of gut microbiota at the phylum, genus and species level among LOP (loperamide) and RIF (rifaximin) groups

Abundance in Group 1: decreased abundance in RIF (rifaximin) group

NCBI Quality ControlLinks
Achromobacter
Actinomycetota
Alistipes
Alistipes sp. cv1
Allobaculum
Bacilli
Bacteria
Bifidobacterium
Bifidobacterium pseudolongum
Candidatus Altimarinota
Candidatus Saccharimonas
Christensenella
Christensenella minuta
Christensenella timonensis
Christensenellaceae
Clostridia
Clostridium
Coriobacteriales
Crenobacter
Desulfovibrio
Desulfovibrionaceae
Dubosiella
Eisenbergiella
Eubacterium coprostanoligenes
Exiguobacterium
Exiguobacterium sp. AT1b
Faecalibaculum
Faecalibaculum rodentium
Ideonella
Lachnospira
Monoglobus
Oscillospiraceae
Parasutterella
Pediococcus
Pediococcus pentosaceus
Peptococcus
Pseudomonadota
Pygmaiobacter
Rikenella
Romboutsia
Romboutsia ilealis
Ruminiclostridium
Sutterellaceae
[Clostridium] leptum
[Eubacterium] brachy
uncultured Clostridium sp.
uncultured Eubacteriales bacterium
Coribacteriaceae UCG 002Coribacteriaceae UCG 002
TuzzerellaTuzzerella
Clostridia UCG 014Clostridia UCG 014
Christensenellaceae R-7 groupChristensenellaceae R-7 group
UCG 010UCG 010

Revision editor(s): Tosin