Lactobacillus salivarius metabolite succinate enhances chicken intestinal stem cell activities via the SUCNR1-mitochondria axis

The activity of intestinal stem cells (ISCs) can be modulated by Lactobacillus, which subsequently affects the mucosal absorptive capacity. However, the underlying mechanisms remain unclear. In this study, a total of 189 Hy-Line Brown chickens (Gallus) were randomly assigned to one of seven experime...

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Main Authors: Danni Luo, Minyao Zou, Xi Rao, Mingping Wei, Lingzhi Zhang, Yuping Hua, Lingzi Yu, Jiajia Cao, Jinyi Ye, Sichao Qi, Huanan Wang, Yuling Mi, Caiqiao Zhang, Jian Li
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:Poultry Science
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Online Access:http://www.sciencedirect.com/science/article/pii/S0032579124013324
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author Danni Luo
Minyao Zou
Xi Rao
Mingping Wei
Lingzhi Zhang
Yuping Hua
Lingzi Yu
Jiajia Cao
Jinyi Ye
Sichao Qi
Huanan Wang
Yuling Mi
Caiqiao Zhang
Jian Li
author_facet Danni Luo
Minyao Zou
Xi Rao
Mingping Wei
Lingzhi Zhang
Yuping Hua
Lingzi Yu
Jiajia Cao
Jinyi Ye
Sichao Qi
Huanan Wang
Yuling Mi
Caiqiao Zhang
Jian Li
author_sort Danni Luo
collection DOAJ
description The activity of intestinal stem cells (ISCs) can be modulated by Lactobacillus, which subsequently affects the mucosal absorptive capacity. However, the underlying mechanisms remain unclear. In this study, a total of 189 Hy-Line Brown chickens (Gallus) were randomly assigned to one of seven experimental groups (n = 27 per group). These groups included a control group, a vehicle group (MRS group), a Lactobacillus salivarius group, a L. salivarius supernatant group, and three succinate treatment groups with various dosages. Each group was further subdivided into three replicates, with 9 chickens per replicate. The results indicate that the administration of Lactobacillus salivarius supernatant to laying hens notably increased the mRNA abundance of the amino acid transporters oligopeptide transporter 1 (PepT1) and sodium-dependent neutral amino acid transporter (B0AT). Metabolomic analyses indicated that the supernatant contains a high concentration of organic acids. Among them, succinate could enhance mRNA abundance of PepT1, B0AT and excitatory amino acid transporters 3 (EAAT3) both in vivo and in vitro. Accordingly, succinate could accelerate intestinal epithelial turnover, as indicated by the increased levels of cyclin-dependent kinase 2 (Cdk2) mRNA and proliferating cell nuclear antigen protein (PCNA), as well as ISC differentiation-related protein leucine-rich repeat containing G protein-coupled receptor 5 (LGR5). Furthermore, succinate treatment was shown to elevate the levels of mitochondrial fusion proteins optic atrophy 1 (OPA1) and translocase of outer mitochondrial membrane 20 (TOMM20), resulting in increased local ATP levels. However, pretreatment with NF-56-EJ40, a succinate receptor antagonist, attenuated the effects of succinate on OPA1, TOMM20, and ATP levels, alone with the reducing LGR5 and PCNA levels. Collectively, succinate, a metabolite of L. salivarius, activates the SUCNR1-mitochondria axis in ISCs, facilitating mitochondrial ATP synthesis, promoting ISC activity, and ultimately enhancing mucosal absorptive capacity.
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spelling doaj-art-3fd76a71f87b452e8c2c34912768e2d32025-08-20T01:48:16ZengElsevierPoultry Science0032-57912025-02-01104210475410.1016/j.psj.2024.104754Lactobacillus salivarius metabolite succinate enhances chicken intestinal stem cell activities via the SUCNR1-mitochondria axisDanni Luo0Minyao Zou1Xi Rao2Mingping Wei3Lingzhi Zhang4Yuping Hua5Lingzi Yu6Jiajia Cao7Jinyi Ye8Sichao Qi9Huanan Wang10Yuling Mi11Caiqiao Zhang12Jian Li13MOA Key Laboratory of Animal Virology, College of Animal Sciences, Zhejiang University, Hangzhou 310058, PR China; Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, PR ChinaMOA Key Laboratory of Animal Virology, College of Animal Sciences, Zhejiang University, Hangzhou 310058, PR China; Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, PR China; Hainan Institute of Zhejiang University, Sanya 572025, PR ChinaQingliu Animal Husbandry, Veterinary and Aquatic Products Center, Sanming 365300, PR ChinaFujian Xin Fengqiang agriculture Co., LTD, Sanming 365300, PR ChinaMOA Key Laboratory of Animal Virology, College of Animal Sciences, Zhejiang University, Hangzhou 310058, PR China; Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, PR ChinaMOA Key Laboratory of Animal Virology, College of Animal Sciences, Zhejiang University, Hangzhou 310058, PR China; Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, PR ChinaMOA Key Laboratory of Animal Virology, College of Animal Sciences, Zhejiang University, Hangzhou 310058, PR China; Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, PR ChinaMOA Key Laboratory of Animal Virology, College of Animal Sciences, Zhejiang University, Hangzhou 310058, PR China; Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, PR ChinaMOA Key Laboratory of Animal Virology, College of Animal Sciences, Zhejiang University, Hangzhou 310058, PR China; Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, PR ChinaMOA Key Laboratory of Animal Virology, College of Animal Sciences, Zhejiang University, Hangzhou 310058, PR China; Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, PR China; Hainan Institute of Zhejiang University, Sanya 572025, PR ChinaMOA Key Laboratory of Animal Virology, College of Animal Sciences, Zhejiang University, Hangzhou 310058, PR China; Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, PR ChinaMOA Key Laboratory of Animal Virology, College of Animal Sciences, Zhejiang University, Hangzhou 310058, PR China; Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, PR ChinaMOA Key Laboratory of Animal Virology, College of Animal Sciences, Zhejiang University, Hangzhou 310058, PR China; Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, PR ChinaMOA Key Laboratory of Animal Virology, College of Animal Sciences, Zhejiang University, Hangzhou 310058, PR China; Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, PR China; Corresponding author.The activity of intestinal stem cells (ISCs) can be modulated by Lactobacillus, which subsequently affects the mucosal absorptive capacity. However, the underlying mechanisms remain unclear. In this study, a total of 189 Hy-Line Brown chickens (Gallus) were randomly assigned to one of seven experimental groups (n = 27 per group). These groups included a control group, a vehicle group (MRS group), a Lactobacillus salivarius group, a L. salivarius supernatant group, and three succinate treatment groups with various dosages. Each group was further subdivided into three replicates, with 9 chickens per replicate. The results indicate that the administration of Lactobacillus salivarius supernatant to laying hens notably increased the mRNA abundance of the amino acid transporters oligopeptide transporter 1 (PepT1) and sodium-dependent neutral amino acid transporter (B0AT). Metabolomic analyses indicated that the supernatant contains a high concentration of organic acids. Among them, succinate could enhance mRNA abundance of PepT1, B0AT and excitatory amino acid transporters 3 (EAAT3) both in vivo and in vitro. Accordingly, succinate could accelerate intestinal epithelial turnover, as indicated by the increased levels of cyclin-dependent kinase 2 (Cdk2) mRNA and proliferating cell nuclear antigen protein (PCNA), as well as ISC differentiation-related protein leucine-rich repeat containing G protein-coupled receptor 5 (LGR5). Furthermore, succinate treatment was shown to elevate the levels of mitochondrial fusion proteins optic atrophy 1 (OPA1) and translocase of outer mitochondrial membrane 20 (TOMM20), resulting in increased local ATP levels. However, pretreatment with NF-56-EJ40, a succinate receptor antagonist, attenuated the effects of succinate on OPA1, TOMM20, and ATP levels, alone with the reducing LGR5 and PCNA levels. Collectively, succinate, a metabolite of L. salivarius, activates the SUCNR1-mitochondria axis in ISCs, facilitating mitochondrial ATP synthesis, promoting ISC activity, and ultimately enhancing mucosal absorptive capacity.http://www.sciencedirect.com/science/article/pii/S0032579124013324Lactobacillus salivariusSuccinateIntestinal stem cellMitochondria
spellingShingle Danni Luo
Minyao Zou
Xi Rao
Mingping Wei
Lingzhi Zhang
Yuping Hua
Lingzi Yu
Jiajia Cao
Jinyi Ye
Sichao Qi
Huanan Wang
Yuling Mi
Caiqiao Zhang
Jian Li
Lactobacillus salivarius metabolite succinate enhances chicken intestinal stem cell activities via the SUCNR1-mitochondria axis
Poultry Science
Lactobacillus salivarius
Succinate
Intestinal stem cell
Mitochondria
title Lactobacillus salivarius metabolite succinate enhances chicken intestinal stem cell activities via the SUCNR1-mitochondria axis
title_full Lactobacillus salivarius metabolite succinate enhances chicken intestinal stem cell activities via the SUCNR1-mitochondria axis
title_fullStr Lactobacillus salivarius metabolite succinate enhances chicken intestinal stem cell activities via the SUCNR1-mitochondria axis
title_full_unstemmed Lactobacillus salivarius metabolite succinate enhances chicken intestinal stem cell activities via the SUCNR1-mitochondria axis
title_short Lactobacillus salivarius metabolite succinate enhances chicken intestinal stem cell activities via the SUCNR1-mitochondria axis
title_sort lactobacillus salivarius metabolite succinate enhances chicken intestinal stem cell activities via the sucnr1 mitochondria axis
topic Lactobacillus salivarius
Succinate
Intestinal stem cell
Mitochondria
url http://www.sciencedirect.com/science/article/pii/S0032579124013324
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