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LimosiLactobacillus pentosus Isolated from Mustard Relieves Drug-induced Constipation in Mice Fed a High-fat Diet by Modulating Enteric Neurotransmitter Function

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Abstract

Functional constipation is one of the most common gastrointestinal disorders. Oxidative stress can aggravate organ dysfunction. Enteric neurotransmitters have significant effects on the regulation of the enteric nervous system and intestinal muscle contraction. Oxidative stress and reduced gastrointestinal motility are considered to be one of the main causes of constipation. This study aimed to investigate whether LimosiLactobacillus pentosus CQZC02 alleviated loperamide hydrochloride (Lop)-induced constipation in mice under high-fat diet (HFD) conditions and to elucidate the underlying mechanism, focusing on enteric neurotransmitters. Four-week-old female BALB/c mice were randomly divided into five groups: normal group (Nor), constipation model group (H-Lop), L. pentosus CQZC02 low-dose group (H-Lop + ZC02L), L. pentosus CQZC02 high-dose group (H-Lop + ZC02H), and LimosiLactobacillus bulgaricus control group (H-Lop + LB). The fecal weight, water content, and total gastrointestinal transit time were measured to determine whether the mice were constipated. Small bowel and colon tissue damage was assessed by hematoxylin and eosin staining, while the degree of damage was determined by double-blind scoring. The levels of serum oxidative stress markers malondialdehyde, superoxide dismutase, glutathione peroxidase, and catalase and neurotransmitters motilin, gastrin, substance P, endothelin, somatostatin, and vasoactive intestinal peptide were measured. The gene expression levels of endothelial nitric oxide synthase, inducible nitric oxide synthase, neuronal nitric oxide synthase, nuclear factor kappa-B, and cyclooxygenase-2 in small intestine tissue were calculated. The constipation symptoms of mice in H-Lop group were manifested by a variety of physiological indicators. In addition, compared with the H-Lop group, H-Lop + ZC02H could effectively relieve the symptoms of constipation in mice. In symptom characterization, the mice in the H-Lop + ZC02H group lost weight and increased feces and water content. In functional experiments, gastrointestinal motility was enhanced; the inflammation score of intestinal tissue was decreased, and gene expression levels were modulated; serum oxidative factor levels were modulated, and oxidative stress levels were decreased.

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Data Availability

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

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Funding

This research was funded by Chongqing University Innovation Research Group Project (CXQTP20033) and Chongqing Kewei Joint Medical Research Project (NO.2021MSXM337).

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Authors and Affiliations

  1. Collaborative Innovation Center for Child Nutrition and Health Development, Chongqing Engineering Research Center of Functional Food, Chongqing Engineering Laboratory for Research and Development of Functional Food, Chongqing University of Education, Chongqing, 400067, China

    Jia Liu, Ruokun Yi, Xingyao Long & Xin Zhao

  2. Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer Hospital, Chongqing, 400030, China

    Shuaiqi Wang, Guangli Luo & Yongpeng He

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  1. Jia Liu
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  6. Xin Zhao
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Contributions

Xin Zhao and Yongpeng He contributed to conception and design of the study. Ruokun Yi performed the statistical analysis. Jia Liu and Shuaiqi Wang wrote the first draft of the manuscript. Xingyao Long and Guangli Luo wrote sections of the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.

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Correspondence to Xin Zhao or Yongpeng He.

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This study was approved by the Ethics Committee of Collaborative Innovation Center for Child Nutrition and Health Development, Chongqing University of Education (2021100101B, Chongqing, China) and followed the national standard of the People’s Republic of China (GB/T 35892–2018) laboratory animal-guidelines for ethical review of animal welfare.

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Liu, J., Wang, S., Yi, R. et al. LimosiLactobacillus pentosus Isolated from Mustard Relieves Drug-induced Constipation in Mice Fed a High-fat Diet by Modulating Enteric Neurotransmitter Function. Probiotics & Antimicro. Prot. 15, 1371–1381 (2023). https://doi.org/10.1007/s12602-022-09991-9

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