Lactobacillus salivarius Promotion of Intestinal Stem Cell Activity in Hens Is Associated with Succinate-Induced Mitochondrial Energy Metabolism

• Published in: mSystems 2022-12, Vol.7 (6), p.e0090322-e0090322
• Main Authors: Zhou, Zhou, Yu, Lingzi, Cao, Jiajia, Yu, Jiaming, Lin, Zhibo, Hong, Yi, Jiang, Sibo, Chen, Cong, Mi, Yuling, Zhang, Caiqiao, Li, Jian
• Format: Article
• Language: English
• Subjects: Amino acids; Animals; Anti-Bacterial Agents - metabolism; Antibiotics; Applied and Industrial Microbiology; Bacteria; Budding; Chickens - microbiology; Energy Metabolism; Female; Inflammation; Intestinal Mucosa; intestinal stem cell; Intestine; Lactobacillus; Lactobacillus salivarius; Ligilactobacillus salivarius; Membrane potential; Metabolism; Metabolites; Metabolomics; Mitochondria; Organoids; Peptides; Phosphorylation; Poultry; Probiotics; Proteins; Reactive oxygen species; Research Article; Stem cells; Stem Cells - metabolism; succinate; Succinic Acid - metabolism
• ISSN: 2379-5077; 2379-5077
• DOI: 10.1128/msystems.00903-22

Currently, the regulation of on intestinal stem cells (ISCs) attracts broad attention, but their active ingredients and the underlying mechanism are worthy of further study. Previously, host intestinal commensal bacteria were verified to drive the differentiation of ISCs. In this study, the strong bacteriostatic activity of Lactobacillus salivarius and were illustrated, and the components (supernatant, precipitation) of or were further demonstrated to decrease the differentiation of ISCs . Interestingly, antibiotics feeding decreased ISCs differentiation as well. However, the administration of supernatant following antibiotics feeding was shown to promote ISCs differentiation dramatically when compared with the antibiotics feeding group, indicating that some active ingredients existed in its supernatant to promote ISCs activity. Strikingly, , the treatment of supernatant was further confirmed to promote the intestinal organoids' size, budding, and LGR5 expression. Next, the metabolomics analysis of supernatants suggested that succinate might be a crucial metabolite to promote ISCs activity. Further, the succinate treatment (1000 μM) and (50 mM) was confirmed to enhance the expression of LGR5 and PCNA. (a sodium/dicarboxylate cotransporter) was detected in the intestinal organoids and demonstrated to transport succinate into ISCs, as confirmed by the contact of FITC-succinate with ISCs nucleus. Subsequently, high mitochondrial membrane potential and reactive oxygen species levels appeared in the intestinal organoids upon succinate treatment. Collectively, the promotion of on ISCs activity is associated with succinate-induced mitochondrial energy metabolism. In our previous study, Lactobacillus salivarius and were demonstrated to regulate intestinal stem cell activity in hens, but their active ingredients and the underlying mechanism remain unclear. In this study, supernatant was shown to directly promote intestinal stem cell activity. Furthermore, the succinate (a critical metabolite of ) was screened out to promote intestinal stem cell activity. Moreover, the succinate was confirmed to enter intestinal stem cells and induce high mitochondrial energy metabolism, finally promoting intestinal stem cell activity. These findings will advance uncovering the mechanism by which regulate intestinal stem cell activity in chickens.