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KJ2020ZD67"]}]},{"name":"The key project of the Natural Science Foundation in College and Universities of Anhui Province of China","award":["NO. KJ2020ZD67"],"award-info":[{"award-number":["NO. KJ2020ZD67"]}]},{"name":"The key project of the Natural Science Foundation in College and Universities of Anhui Province of China","award":["NO. KJ2020ZD67"],"award-info":[{"award-number":["NO. KJ2020ZD67"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Microbiol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>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.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Method<\/jats:title>\n                <jats:p>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\u2009+\u2009L-PA) treatment groups (6 mice per group). The mice in the Lop\u2009+\u2009L-PA group were given L-PA (250\u00a0mg\/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.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>45 differential metabolites and 18 significantly different microbiota were found in FC children. The \u03b1 and \u03b2 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 <jats:italic>Ochrobactrum<\/jats:italic>, and N6, N6, N6-trimethyl-l-lysine was positively associated with <jats:italic>Phascolarcrobacterium<\/jats:italic>. 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.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Gut microbiota and serum metabolites were significantly altered in children with FC. The abundance of <jats:italic>Phascolarctobacterium<\/jats:italic> and <jats:italic>Ochrobactrum<\/jats:italic> 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.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12866-023-02880-3","type":"journal-article","created":{"date-parts":[[2023,5,20]],"date-time":"2023-05-20T05:01:55Z","timestamp":1684558915000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Protective effect of L-pipecolic acid on constipation in C57BL\/6 mice based on gut microbiome and serum metabolomic"],"prefix":"10.1186","volume":"23","author":[{"given":"Huan","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-yun","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-ping","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping-ping","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-jie","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,5,20]]},"reference":[{"key":"2880_CR1","unstructured":"Diaz S, Bittar K, Mendez MD. 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