Zheng Liqin, Xin Jinge, Ye Huiqian, Sun Ning, Gan Baoxing, Gong Xuemei, Bao Shusheng, Xiang Min, Wang Hesong, Ni Xueqin, Li Hao, Zhang Tao
School of Life Science and Technology, High-Field Magnetic Resonance Brain Imaging Key Laboratory of Sichuan Province, University of Electronic Science and Technology of China, Chengdu, China.
MOE Key Lab for Neuroinformation, Sichuan Institute for Brain Science and Brain-Inspired Intelligence, University of Electronic Science and Technology of China, 2006 Xiyuan Avenue, West Hi-Tech Zone, Chengdu , Sichuan, 611731, China.
BMC Microbiol. 2025 Apr 2;25(1):191. doi: 10.1186/s12866-025-03893-w.
Based on the microbiota-gut-brain axis (MGBA) hypothesis, probiotics play an increasingly important role in treating various psychiatric disorders. Schizophrenia (SCZ) is a common mental disease with a complex pathogenesis and is challenging to treat. Although studies have elucidated the mechanisms associated with the interactions between the microbiota-gut-brain axis and SCZ, few have specifically used probiotics as a therapeutic intervention for SCZ. Accordingly, the current study determines whether L. johnsonii YH1136 effectively prevents SCZ-like behavior in mice and identifies the associated key microbes and metabolites. An SCZ mouse model was established by intraperitoneal injection of MK-801; L. johnsonii YH1136 was administered via oral gavage. L. johnsonii YH1136 significantly improves abnormal behaviors, including psychomotor hyperactivity and sociability and alleviates aberrant enzyme expression associated with tryptophan metabolism in SCZ mice. Additionally, L. johnsonii YH1136 upregulates hippocampal brain-derived neurotrophic factor (BDNF) levels while downregulating tryptophan 2,3-dioxygenase (TDO2), indoleamine-pyrrole 2,3-dioxygenase 1 (IDO1), kynurenine aminotransferase 1 (KAT1). Subsequent 16S rRNA sequencing of intestinal contents suggests that L. johnsonii YH1136 modulates the gut flora structure and composition by increasing the relative abundance of Lactobacillus and decreasing Dubosiella in SCZ mice. N-acetylneuraminic acid and hypoxanthine are the key serum metabolites mediating the interaction between the MGBA and SCZ. These results partially reveal the mechanism underlying the effects of L. johnsonii YH1136 on SCZ-like behavior in mice, supporting the development of therapeutic L. johnsonii probiotic formulations against SCZ.
基于微生物群-肠道-脑轴（MGBA）假说，益生菌在治疗各种精神疾病中发挥着越来越重要的作用。精神分裂症（SCZ）是一种常见的精神疾病，发病机制复杂，治疗具有挑战性。尽管已有研究阐明了微生物群-肠道-脑轴与SCZ之间相互作用的相关机制，但很少有研究专门将益生菌用作SCZ的治疗干预措施。因此，本研究确定约氏乳杆菌YH1136是否能有效预防小鼠的SCZ样行为，并确定相关的关键微生物和代谢产物。通过腹腔注射MK-801建立SCZ小鼠模型；通过灌胃给予约氏乳杆菌YH1136。约氏乳杆菌YH1136显著改善异常行为，包括精神运动性多动和社交能力，并减轻SCZ小鼠中与色氨酸代谢相关的异常酶表达。此外，约氏乳杆菌YH1136上调海马脑源性神经营养因子（BDNF）水平，同时下调色氨酸2,3-双加氧酶（TDO2）、吲哚胺-吡咯2,3-双加氧酶1（IDO1）、犬尿氨酸转氨酶1（KAT1）。随后对肠道内容物进行的16S rRNA测序表明，约氏乳杆菌YH1136通过增加SCZ小鼠中乳酸杆菌的相对丰度和减少杜波氏菌来调节肠道菌群结构和组成。N-乙酰神经氨酸和次黄嘌呤是介导MGBA与SCZ相互作用的关键血清代谢产物。这些结果部分揭示了约氏乳杆菌YH1136对小鼠SCZ样行为产生影响的潜在机制，支持开发针对SCZ的约氏乳杆菌益生菌治疗制剂。
