Metabolites 13,14‐Dihydro‐15‐keto‐PGE2 Participates in Bifidobacterium animalis F1‐7 to Alleviate Opioid‐Induced Constipation by 5‐HT Pathway

Author:

Lu Youyou12ORCID,Zhou Xiaohong3,Wu Yeting4,Cui Qingyu5,Tian Xiaoying5,Yi Huaxi5ORCID,Gong Pimin5,Zhang Lanwei5ORCID

Affiliation:

1. College of Food Science and Technology Huazhong Agricultural University Wuhan 430070 China

2. Key Laboratory of Environment Correlative Dietology Ministry of Education (Huazhong Agricultural University) China

3. Qingdao Central Hospital Qingdao 266042 China

4. College of Animal Science and Veterinary Medicine Huazhong Agricultural University Wuhan 430070 China

5. College of Food Science and Engineering Ocean University of China Qingdao 266000 China

Abstract

ScopePeople suffer from constipation caused by many factors, including constipation (Opioid‐Induced Constipation, OIC) during analgesic treatment. Microorganisms may be a potent solution to this problem, but the mechanism is still unclear.Methods and resultsBased on models in vivo and in vitro, the potential mechanism involving Bifidobacterium animalis F1‐7 (B. animalis F1‐7), screened in the previous studies, is explored through non‐targeted metabonomics, electrophysiological experiment and molecular level docking. The results showed that B. animalis F1‐7 effectively alleviates OIC and promotes the expression of chromogranin A (CGA) and 5‐hydroxytryptamine (5‐HT). The metabolite 13,14‐dihydro‐15‐keto‐PGE2 related to B. animalis F1‐7 is found, which has a potential improvement effect on OIC at 20 mg kg BW−1 in vivo. At 30 ng mL−1 it effectively stimulates secretion of CGA/5‐HT (408.95 ± 1.18 ng mL−1) by PC‐12 cells and changes the membrane potential potassium ion current without affecting the sodium ion current in vitro. It upregulates the target of free fatty acid receptor‐4 protein(FFAR4/β‐actin, 0.81 ± 0.02).ConclusionThe results demonstrate that metabolite 13,14‐dihydro‐15‐keto‐PGE2 participated in B. animalis F1‐7 to alleviate OIC via the 5‐HT pathway.

Funder

National Natural Science Foundation of China

Fundamental Research Funds for the Central Universities

National Key Research and Development Program of China

Publisher

Wiley

Subject

Food Science,Biotechnology

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