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

  • Mol Nutr Food Res. 2024 Feb;68(3):e2200846. doi: 10.1002/mnfr.202200846.
Youyou Lu  1  2 ,  Xiaohong Zhou  3 ,  Yeting Wu  4 ,  Qingyu Cui  5 ,  Xiaoying Tian  5 ,  Huaxi Yi  5 ,  Pimin Gong  5 ,  Lanwei Zhang  5
Affiliations
  • 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.
PMID: 38054625 DOI: 10.1002/mnfr.202200846
Abstract

Scope: People 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 results: Based 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).

Conclusion: The results demonstrate that metabolite 13,14-dihydro-15-keto-PGE2 participated in B. animalis F1-7 to alleviate OIC via the 5-HT pathway.

Keywords
13,14-Dihydro-15-keto-PGE2; 5-HT pathway; Bifidobacterium animalis F1-7; constipation; metabolites.
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