Protective effect of L-pipecolic acid on constipation in C57BL/6 mice based on gut microbiome and serum metabolomic

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Needs review
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
Authors
Li H, Xiao HY, Yuan LP, Yan B, Pan Y, Tian PP, Zhang WJ
Journal
BMC microbiology
Year
2023
Keywords:
Children, Functional constipation, Gut microbiota, L-pipecolic acid, Metabolite profiles
BACKGROUND: Functional constipation (FC) in children affects their growth, development and quality of life. L-pipecolic acid (L-PA) was decreased in FC children based on gut microbiome and serum metabolomic. In this study, loperamide-induced constipation in mice was used to evaluate the effects of L-PA on constipated mice. METHOD: 26 FC and 28 healthy children were recruited. Stool samples and serum samples were subjected to 16S rDNA sequencing and ultra-performance liquid chromatography/quadrupole time of flight (UPLC-Q/TOF-MS) approach, respectively. A loperamide-induced mouse constipation model was developed, and all mice were randomly divided into control (Con), loperamide (Lop) and L-PA (Lop + L-PA) treatment groups (6 mice per group). The mice in the Lop + L-PA group were given L-PA (250 mg/kg, once a day) and loperamide; the Lop group was given loperamide for 1 week, and the Con group was given saline. The fecal parameters and intestinal motility of mice in each group were detected. serum 5-HT levels and colon 5-HT expression were detected by ELISA and immunohistochemistry, respectively; qRT-PCR was used to detect the expression of AQP3 and 5-HT4R mRNA in each group. RESULTS: 45 differential metabolites and 18 significantly different microbiota were found in FC children. The α and β diversity of gut microbiota in FC children was significantly reduced. Importantly, serum L-PA was significantly reduced in FC children. The KEGG pathway enrichment were mainly enriched in fatty acid biosynthesis, lysine degradation, and choline metabolism. L-PA was negatively associated with Ochrobactrum, and N6, N6, N6-trimethyl-l-lysine was positively associated with Phascolarcrobacterium. In addition, L-PA improved the fecal water content, intestinal transit rate, and increased the serum 5-HT levels in constipated mice. Moreover, L-PA increased the expression of 5-HT4R, reduced AQP3, and regulated constipation-associated genes. CONCLUSIONS: Gut microbiota and serum metabolites were significantly altered in children with FC. The abundance of Phascolarctobacterium and Ochrobactrum and serum L-PA content were decreased in FC children. L-PA was found to alleviate the fecal water content, increase intestinal transit rate and the first black stool defecation time. L-PA improved constipation by increasing 5-HT and 5-HT4R expression while down-regulating AQP3 expression.

Experiment 1


Needs review

Curated date: 2025/03/14

Curator: Mautin

Revision editor(s): Mautin

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
Constipation Constipation,Costiveness,Dyschezia,constipation
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
Functional Constipation(FC)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
children/patients with functional constipation, with infrequent bowel movements and who fulfilled the Roman IV diagnostic criteria
Group 0 sample size Number of subjects in the control (unexposed) group
28
Group 1 sample size Number of subjects in the case (exposed) group
26
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
3 months.

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V3-V4

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances
Statistical test
T-Test
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05

Alpha Diversity

Chao1 Abundance-based estimator of species richness
decreased

Signature 1

Needs review

Curated date: 2025/03/16

Curator: Mautin

Revision editor(s): Mautin

Source: Figure 1F

Description: The Differential analysis between healthy Controls and Functional constipation using STAMP Analysis

Abundance in Group 1: increased abundance in Functional Constipation(FC)

NCBI Quality ControlLinks
Acetanaerobacterium
Eubacterium
Intestinimonas
Klebsiella
Ruminiclostridium
Ruminococcaceae UCG-005Ruminococcaceae UCG-005
Ruminococcaceae NK4A214Ruminococcaceae NK4A214
Ruminiclostridium 9Ruminiclostridium 9
Lachnospiraceae UCG-010Lachnospiraceae UCG-010
Ruminococcaceae UCG-004Ruminococcaceae UCG-004

Revision editor(s): Mautin

Signature 2

Needs review

Curated date: 2025/03/16

Curator: Mautin

Revision editor(s): Mautin

Source: Figure 1F

Description: The Differential analysis between healthy Controls and Functional constipation using STAMP Analysis

Abundance in Group 1: decreased abundance in Functional Constipation(FC)

NCBI Quality ControlLinks
Bacillus
Gemella
Halomonas
Ochrobactrum
Phascolarctobacterium
Phenylobacterium

Revision editor(s): Mautin