Namihira Masakazu, Inoue Nana, Watanabe Yohei, Hayashi Takuto, Murotomi Kazutoshi, Hirayama Kazuhiro, Sato Naoki
Molecular Neurophysiology Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Ibaraki 305-8566, Japan.
TOA Biopharma Co. Ltd., Tokyo 151-0073, Japan.
Stem Cells. 2025 Feb 12;43(2). doi: 10.1093/stmcls/sxae077.
Gut microbiota plays an important role in regulating brain function and adult neurogenesis. Although probiotics have recently been reported as effective against certain psychiatric disorders, the underlying mechanisms remain unclear. In particular, the combination of 3 probiotic strains, Bacillus subtilis TO-A, Enterococcus faecium T-110, and Clostridium butyricum TO-A, hereafter referred to as ProB3, has been reported to potentially alleviate psychiatric symptoms in patients with schizophrenia. Herein, we show that ProB3 promotes adult neurogenesis in mice and restores its dysregulation in germ-free (GF) mice. ProB3 colonization in GF mice enhanced the proliferation of adult neural stem cells compared to specific-pathogen-free and GF mice. Furthermore, ProB3 colonization was sufficient to ameliorate the arrest of newborn neuron maturation and the diminution of quiescent neural stem cells in GF mice. ProB3 colonization in mice increased the levels of several metabolites in the blood, including theanine and 3-hydroxybutyrate, and imidazole peptides, including anserine, which promoted proliferation, neurogenesis, and maturation of newborn neurons in cultured human fetus neural stem cells, as well as mouse adult hippocampal neural stem cells. Collectively, these results indicate that the essential role of the gut microbiota in adult hippocampal neurogenesis can be effectively complemented by the intake of a specific 3-strain probiotic, ProB3, providing novel insights into the brain-gut axis.
肠道微生物群在调节大脑功能和成人神经发生中起重要作用。尽管最近有报道称益生菌对某些精神疾病有效，但其潜在机制仍不清楚。特别是，已报道三种益生菌菌株枯草芽孢杆菌TO - A、粪肠球菌T - 110和丁酸梭菌TO - A（以下简称ProB3）的组合可能减轻精神分裂症患者的精神症状。在此，我们表明ProB3可促进小鼠的成人神经发生，并恢复无菌（GF）小鼠中其失调的情况。与无特定病原体小鼠和GF小鼠相比，GF小鼠中的ProB3定殖增强了成人神经干细胞的增殖。此外，ProB3定殖足以改善GF小鼠中新生神经元成熟的停滞以及静止神经干细胞的减少。小鼠中的ProB3定殖增加了血液中几种代谢物的水平，包括茶氨酸和3 - 羟基丁酸，以及咪唑肽，包括鹅肌肽，这些物质促进了培养的人类胎儿神经干细胞以及小鼠成体海马神经干细胞中新生神经元的增殖、神经发生和成熟。总体而言，这些结果表明，肠道微生物群在成人海马神经发生中的重要作用可以通过摄入特定的三菌株益生菌ProB3得到有效补充，为脑 - 肠轴提供了新的见解。
