Protective effect of L-pipecolic acid on constipation in C57BL/6 mice based on gut microbiome and serum metabolomic
Abstract 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 effe...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-05-01
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| Series: | BMC Microbiology |
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| Online Access: | https://doi.org/10.1186/s12866-023-02880-3 |
| _version_ | 1797823009361231872 |
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| author | Huan Li Hong-yun Xiao Li-ping Yuan Bo Yan Ying Pan Ping-ping Tian Wei-jie Zhang |
| author_facet | Huan Li Hong-yun Xiao Li-ping Yuan Bo Yan Ying Pan Ping-ping Tian Wei-jie Zhang |
| author_sort | Huan Li |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-13T10:16:38Z |
| format | Article |
| id | doaj.art-48b3ca4acbf34a04a6194e706a7ec7dc |
| institution | Directory Open Access Journal |
| issn | 1471-2180 |
| language | English |
| last_indexed | 2024-03-13T10:16:38Z |
| publishDate | 2023-05-01 |
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| series | BMC Microbiology |
| spelling | doaj.art-48b3ca4acbf34a04a6194e706a7ec7dc2023-05-21T11:10:09ZengBMCBMC Microbiology1471-21802023-05-0123111110.1186/s12866-023-02880-3Protective effect of L-pipecolic acid on constipation in C57BL/6 mice based on gut microbiome and serum metabolomicHuan Li0Hong-yun Xiao1Li-ping Yuan2Bo Yan3Ying Pan4Ping-ping Tian5Wei-jie Zhang6Department of Pediatrics, First Affiliated Hospital of Anhui Medical UniversityDepartment of Pediatrics, First Affiliated Hospital of Anhui Medical UniversityDepartment of Pediatrics, First Affiliated Hospital of Anhui Medical UniversityDepartment of Technology, Anhui Medical CollegeDepartment of Technology, Anhui Medical CollegeDepartment of Technology, Anhui Medical CollegeDepartment of Technology, Anhui Medical CollegeAbstract 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.https://doi.org/10.1186/s12866-023-02880-3Functional constipationGut microbiotaMetabolite profilesL-pipecolic acidChildren |
| spellingShingle | Huan Li Hong-yun Xiao Li-ping Yuan Bo Yan Ying Pan Ping-ping Tian Wei-jie Zhang Protective effect of L-pipecolic acid on constipation in C57BL/6 mice based on gut microbiome and serum metabolomic BMC Microbiology Functional constipation Gut microbiota Metabolite profiles L-pipecolic acid Children |
| title | Protective effect of L-pipecolic acid on constipation in C57BL/6 mice based on gut microbiome and serum metabolomic |
| title_full | Protective effect of L-pipecolic acid on constipation in C57BL/6 mice based on gut microbiome and serum metabolomic |
| title_fullStr | Protective effect of L-pipecolic acid on constipation in C57BL/6 mice based on gut microbiome and serum metabolomic |
| title_full_unstemmed | Protective effect of L-pipecolic acid on constipation in C57BL/6 mice based on gut microbiome and serum metabolomic |
| title_short | Protective effect of L-pipecolic acid on constipation in C57BL/6 mice based on gut microbiome and serum metabolomic |
| title_sort | protective effect of l pipecolic acid on constipation in c57bl 6 mice based on gut microbiome and serum metabolomic |
| topic | Functional constipation Gut microbiota Metabolite profiles L-pipecolic acid Children |
| url | https://doi.org/10.1186/s12866-023-02880-3 |
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