Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan University, No. 16, 3rd section, South Renmin Road, Wuhou District, Chengdu, 610041, Sichuan, People's Republic of China.
Department of Clinical Nutrition, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
BMC Neurosci. 2022 Jun 26;23(1):38. doi: 10.1186/s12868-022-00724-w.
Critical development period of intestinal microbiota occurs concurrently with brain development, and their interaction is influenced by the microbiota-gut-brain axis. This study examined how antibiotics exposure affected gut microbiota and brain development and analyzed the possible benefits of heat-inactivated Lacticaseibacillus paracasei N1115 (N1115). Thirty neonatal male mice were randomly divided into three groups and treated with sterilized water (control), an antibiotic cocktail (Abx), or antibiotics plus heat-inactivated N1115 (Abx + N1115) for 84 days. We found that while the mRNA levels of GABA, GABA, and glucocorticoid receptor (GR) in the hippocampus and brain-derived neurotrophic factor (BDNF), GABA, GABA, and nerve growth factor (NGF) in the prefrontal cortex were higher, the mRNA levels of 5-HT were lower in the Abx group. The Abx + N1115 group had lower mRNA levels of GABA, GABA, and GR in the hippocampus and BDNF, GABA, and NGF in the prefrontal cortex than the Abx group. The latency period was longer in the Morris water maze test while longer rest time was seen in tail suspension test in the Abx group than the control and Abx + N1115 groups. In the open field test, the moving time and distance of the Abx group were reduced. Further, the alpha-diversity indexes of the Abx and Abx + N1115 groups were significantly lower than the control. Further, long-term exposure to antibiotics disrupted the intestinal microbiota as evidenced by decreased Bacteroides, Firmicutes, and Lactobacillus, and increased Proteobacteria and Citrobacter. However, N1115 significantly decreased the abundance of Citrobacter when compared with those in the Abx group. These results indicate that antibiotics can substantially damage the intestinal microbiota and cognitive function, causing anxiety and depression, which can be alleviated by heat-inactivated N1115 via modulation of the microbiota-gut-brain axis.
肠道微生物群的关键发育期与大脑发育同时发生，它们的相互作用受微生物群-肠道-大脑轴的影响。本研究探讨了抗生素暴露如何影响肠道微生物群和大脑发育，并分析了热灭活副干酪乳杆菌 N1115（N1115）的可能益处。将 30 只新生雄性小鼠随机分为三组，分别用无菌水（对照）、抗生素混合物（Abx）或抗生素加热灭活 N1115（Abx+N1115）处理 84 天。结果发现，虽然 Abx 组海马和脑源性神经营养因子（BDNF）中 GABA、GABA 和糖皮质激素受体（GR）的 mRNA 水平较高，而前额叶皮质中 5-HT 的 mRNA 水平较低，但 Abx+N1115 组海马和前额叶皮质中 GABA、GABA 和 GR 的 mRNA 水平低于 Abx 组。Abx 组在 Morris 水迷宫测试中的潜伏期较长，在悬尾测试中的休息时间也较长。与对照组和 Abx+N1115 组相比，Abx 组在旷场测试中的移动时间和距离减少。此外，Abx 和 Abx+N1115 组的 alpha 多样性指数显著低于对照组。进一步研究表明，长期暴露于抗生素会破坏肠道微生物群，表现为拟杆菌、厚壁菌和乳酸杆菌减少，变形菌和柠檬酸杆菌增加。然而，与 Abx 组相比，N1115 显著降低了柠檬酸杆菌的丰度。这些结果表明，抗生素可以显著损害肠道微生物群和认知功能，导致焦虑和抑郁，而热灭活 N1115 可以通过调节微生物群-肠道-大脑轴来缓解这些问题。
