Modulation of gut microbiota and intestinal metabolites by lactulose improves loperamide-induced constipation in mice
Autor: | Xiaoyu Zhang, Kong Mingwang, Xinkun Bao, Hongtao Liu, Cheng Xue, Junping Zheng, Guangjun Sun, Aizhen Lin, Nan Jiang |
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Rok vydání: | 2021 |
Předmět: |
Loperamide
Constipation medicine.medical_treatment Laxative Pharmaceutical Science Inflammation 02 engineering and technology Pharmacology Gut flora digestive system 030226 pharmacology & pharmacy Mice 03 medical and health sciences Lactulose 0302 clinical medicine medicine Animals Mice Inbred BALB C biology Chemistry Prebiotic Therapeutic effect 021001 nanoscience & nanotechnology biology.organism_classification Gastrointestinal Microbiome medicine.symptom 0210 nano-technology medicine.drug |
Zdroj: | European Journal of Pharmaceutical Sciences. 158:105676 |
ISSN: | 0928-0987 |
DOI: | 10.1016/j.ejps.2020.105676 |
Popis: | Lactulose is a common laxative and has been widely applied to clinical treatment for constipation. This study aimed to explore the improving effect of lactulose on constipation through the mediation of gut microbiota and intestinal metabolites. BALB/c mice with constipation induced by loperamide were orally treated with lactulose for four weeks. After the treatment, the constipation-related factors were determined. The effect of lactulose on the composition of gut microbiota was assessed by 16S rDNA gene sequencing. Gas chromatography or liquid chromatography-mass spectrometer (GC/LC-MS) analysis was used for the quantification of intestinal metabolites. The treatment of constipated mice with lactulose accelerated intestinal motility, suppressed inflammatory responses, protected gut barrier, and improved metabolisms of water and salt in the intestinal tract. These therapeutic effects were attributed to the reversed gut microbiota dysfunction, which conferred the benefit to the production of intestinal metabolites including bile acids, short-chain fatty acids, and tryptophan catabolites. Further, the depletion of intestinal flora from loperamide- or (loperamide + lactulose)-treated mice confirmed the significance of gut microbiota in the mediation of constipation. In summary, this study leads us to propose that lactulose may improve constipation through a prebiotic effect on gut microbiota and intestinal metabolites. |
Databáze: | OpenAIRE |
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