The Farncombe Family Digestive Health Institute, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.
Gastroenterology. 2011 Aug;141(2):599-609, 609.e1-3. doi: 10.1053/j.gastro.2011.04.052. Epub 2011 Apr 30.
BACKGROUND & AIMS: Alterations in the microbial composition of the gastrointestinal tract (dysbiosis) are believed to contribute to inflammatory and functional bowel disorders and psychiatric comorbidities. We examined whether the intestinal microbiota affects behavior and brain biochemistry in mice.
Specific pathogen-free (SPF) BALB/c mice, with or without subdiaphragmatic vagotomy or chemical sympathectomy, or germ-free BALB/c mice received a mixture of nonabsorbable antimicrobials (neomycin, bacitracin, and pimaricin) in their drinking water for 7 days. Germ-free BALB/c and NIH Swiss mice were colonized with microbiota from SPF NIH Swiss or BALB/c mice. Behavior was evaluated using step-down and light preference tests. Gastrointestinal microbiota were assessed using denaturing gradient gel electrophoresis and sequencing. Gut samples were analyzed by histologic, myeloperoxidase, and cytokine analyses; levels of serotonin, noradrenaline, dopamine, and brain-derived neurotropic factor (BDNF) were assessed by enzyme-linked immunosorbent assay.
Administration of oral antimicrobials to SPF mice transiently altered the composition of the microbiota and increased exploratory behavior and hippocampal expression of BDNF. These changes were independent of inflammatory activity, changes in levels of gastrointestinal neurotransmitters, and vagal or sympathetic integrity. Intraperitoneal administration of antimicrobials to SPF mice or oral administration to germ-free mice did not affect behavior. Colonization of germ-free BALB/c mice with microbiota from NIH Swiss mice increased exploratory behavior and hippocampal levels of BDNF, whereas colonization of germ-free NIH Swiss mice with BALB/c microbiota reduced exploratory behavior.
The intestinal microbiota influences brain chemistry and behavior independently of the autonomic nervous system, gastrointestinal-specific neurotransmitters, or inflammation. Intestinal dysbiosis might contribute to psychiatric disorders in patients with bowel disorders.
人们认为胃肠道（肠道失调）微生物组成的改变会导致炎症和功能性肠病以及精神共病。我们研究了肠道微生物群是否会影响小鼠的行为和大脑生化。
无特定病原体（SPF）BALB/c 小鼠，有无膈下迷走神经切断术或化学交感神经切除术，或无菌 BALB/c 小鼠在饮用水中接受非吸收性抗生素（新霉素、杆菌肽和匹马霉素）混合物 7 天。无菌 BALB/c 和 NIH 瑞士小鼠用 SPF NIH 瑞士或 BALB/c 小鼠的微生物群定植。使用下台阶和光偏好测试评估行为。使用变性梯度凝胶电泳和测序评估胃肠道微生物群。通过组织学、髓过氧化物酶和细胞因子分析分析肠道样本；通过酶联免疫吸附试验评估 5-羟色胺、去甲肾上腺素、多巴胺和脑源性神经营养因子（BDNF）的水平。
向 SPF 小鼠口服抗生素可暂时改变微生物群的组成，并增加探索行为和海马体 BDNF 的表达。这些变化与炎症活性、胃肠道神经递质水平的变化以及迷走神经或交感神经完整性无关。向 SPF 小鼠腹腔内给予抗生素或向无菌小鼠口服抗生素均不会影响行为。无菌 BALB/c 小鼠用 NIH 瑞士小鼠的微生物群定植可增加探索行为和海马体 BDNF 的水平，而无菌 NIH 瑞士小鼠用 BALB/c 微生物群定植可减少探索行为。
肠道微生物群独立于自主神经系统、胃肠道特异性神经递质或炎症影响大脑化学和行为。肠道失调可能导致患有肠病的患者出现精神障碍。
