<p>Antibiotics (AB) are widely abused in medicine and may be a risk factor for mental health. To better understand their effects, we observed mental disorder symptoms in AB-treated mice and patients, and investigated possible mechanisms. Using AB-treated mice, we found obvious anxiety-like behaviors, along with differential gut microbiota (mainly <i>Firmicutes</i> and <i>Bacteroidota</i>), reduced short-chain fatty acids (SCFAs), and disrupted gut-brain lipid metabolism. Acetylcholine decreased in feces, colon wall, serum, and hippocampus of AB-treated mice, and this reduction was significantly correlated with anxiety-like behaviors. Moreover, using AB-treated patients (n = 55), AB-naïve patients (n = 60), and healthy controls (n = 60), we also observed the obvious anxiety symptoms in AB-treated patients, along with differential gut microbiota (mainly <i>Firmicutes</i>), reduced SCFAs, and disrupted lipid metabolism in feces and serum. AB-treated patients showed consistently lower serum and fecal acetylcholine, which was highly correlated with anxiety symptoms. In both AB-treated mice and patients, co-occurrence analysis indicated that the “<i>Bacteroides</i>-acetylcholine” pair may play an important role in AB-induced anxiety. At the species levels, <i>Bacteroides_caecimuris</i> in AB-treated mice and <i>Bacteroides_plebeius</i> in AB-treated patients were both decreased and significantly correlated with acetylcholine. Furthermore, exogenous methacholine (an acetylcholine derivative) intervention effectively alleviated anxiety-like behaviors and suppressed hippocampal microglial activation in AB-treated mice. Together, our findings highlight the harmful effects of aggressive AB treatment on mood and show the potential of acetylcholine or its derivative to reverse this effect.</p>

错误:搜索内容不能为空,请输入英文关键词
错误:关键词超出字数限制,请精简
高级检索

Consistent decline of acetylcholine in microbiota-gut-brain axis mediates antibiotic-induced anxiety via regulating hippocampus microglial activation

  • Ke Xu,
  • Yi Ren,
  • Shuang Zhao,
  • Zhe Ren,
  • Jiaolin Wang,
  • Dianji Tu,
  • Fei He,
  • Jinzhou Feng,
  • Wentao Wu,
  • Qi Zhong,
  • Jianjun Chen,
  • Peng Xie

摘要

Antibiotics (AB) are widely abused in medicine and may be a risk factor for mental health. To better understand their effects, we observed mental disorder symptoms in AB-treated mice and patients, and investigated possible mechanisms. Using AB-treated mice, we found obvious anxiety-like behaviors, along with differential gut microbiota (mainly Firmicutes and Bacteroidota), reduced short-chain fatty acids (SCFAs), and disrupted gut-brain lipid metabolism. Acetylcholine decreased in feces, colon wall, serum, and hippocampus of AB-treated mice, and this reduction was significantly correlated with anxiety-like behaviors. Moreover, using AB-treated patients (n = 55), AB-naïve patients (n = 60), and healthy controls (n = 60), we also observed the obvious anxiety symptoms in AB-treated patients, along with differential gut microbiota (mainly Firmicutes), reduced SCFAs, and disrupted lipid metabolism in feces and serum. AB-treated patients showed consistently lower serum and fecal acetylcholine, which was highly correlated with anxiety symptoms. In both AB-treated mice and patients, co-occurrence analysis indicated that the “Bacteroides-acetylcholine” pair may play an important role in AB-induced anxiety. At the species levels, Bacteroides_caecimuris in AB-treated mice and Bacteroides_plebeius in AB-treated patients were both decreased and significantly correlated with acetylcholine. Furthermore, exogenous methacholine (an acetylcholine derivative) intervention effectively alleviated anxiety-like behaviors and suppressed hippocampal microglial activation in AB-treated mice. Together, our findings highlight the harmful effects of aggressive AB treatment on mood and show the potential of acetylcholine or its derivative to reverse this effect.