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. 2021 May 11:15:1971-1980.
doi: 10.2147/DDDT.S309675. eCollection 2021.

Inhibitory Effect of Lactococcus lactis subsp. lactis HFY14 on Diphenoxylate-Induced Constipation in Mice by Regulating the VIP-cAMP-PKA-AQP3 Signaling Pathway

Qian Tan #  1   2 , Jing Hu #  3 , Yujing Zhou  1   2 , Yunxiao Wan  1   2 , Chuanlan Zhang  1   2 , Xin Liu  1   2 , Xingyao Long  1   4 , Fang Tan  5 , Xin Zhao  1
Affiliations

Inhibitory Effect of Lactococcus lactis subsp. lactis HFY14 on Diphenoxylate-Induced Constipation in Mice by Regulating the VIP-cAMP-PKA-AQP3 Signaling Pathway

Qian Tan et al. Drug Des Devel Ther. .

Abstract

Aim: The naturally fermented yak yogurt of pastoralists in the Tibetan Plateau, China, because of its unique geographical environment and the unique lifestyle of Tibetan pastoralists, is very different from other kinds of sour milk, and the microorganisms it contains are special. Lactococcus lactis subsp. lactis HFY14 (LLSL-HFY14) is a new lactic acid bacterium isolated from naturally fermented yak yogurt. The purpose of this study was to study the inhibitory effect of the bacterium on constipation.

Methods: Constipation was induced in ICR mice with diphenoxylate, and the constipated mice were treated with LLSL-HFY14. The weight and feces of the mice were visually detected. Colonic tissues were observed on hematoxylin and eosin-stained sections. Serum indices were detected with kits. mRNA expression in the colon was determined by quantitative polymerase chain reaction assay.

Results: Constipation caused weight loss, the number of defecation granules, defecation weight, fecal water content decreased, and the first black stool excretion time increased. LLSL-HFY14 alleviated these symptoms, and the effects were similar to those of lactulose (drug). The pathological examination revealed that constipation caused pathological changes in the colon, and LLSL-HFY14 effectively alleviated the disease. LLSL-HFY14 increased serum levels of motilin, gastrin, endothelin, substance P, acetylcholinesterase, and vasoactive intestinal peptide (VIP) and decreased serum levels of somatostatin in constipated mice. In addition, LLSL-HFY14 upregulated VIP, cAMP, protein kinase A, and aquaporin 3 expression in colonic tissues of constipated mice in a dose-dependent manner.

Conclusion: LLSL-HFY14 inhibited constipation, similar to lactulose, and has the potential to become a biological agent.

Keywords: constipation; diphenoxylate; lactic acid bacterium; mice; yak yogurt.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Body weights of the constipated mice. a–dMean values with different letters are significantly different (P < 0.05) based on Tukey’s test.
Figure 2
Figure 2
Discharge time of the first black stool by constipated mice at the end of eighth week. a–dMean values with different letters are significantly different (P < 0.05) based on Tukey’s test.
Figure 3
Figure 3
Hematoxylin and eosin (H&E) pathological staining status of colonic tissues from constipated mice. The black arrow indicates the damaged tissue.
Figure 4
Figure 4
Vasoactive intestinal peptide (VIP), cAMP, protein kinase A (PKA), and aquaporin 3 (AQP3) mRNA expression in colonic tissues from constipated mice. a–dMean values with different letters are significantly different (P < 0.05) based on Tukey’s test.
See this image and copyright information in PMC

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