Work

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

Year: 2024

Type: article

Abstract: 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 ( B 0 AT ). Metabolomic analyses indicated that the supernatant contains a high concentration of organic acids. Among them, succinate could enhance mRNA abundance of PepT1, B 0 AT 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.

Source: Poultry Science

DOI: 10.1016/j.psj.2024.104754