Changes in short-chain fatty acids affect brain development in mice with early life antibiotic-induced dysbacteriosis

作者：Qixing Zhang, Han Li, Shuang Yin, Xiao Feng, Gong Chen, Jie Zhou, Kangkang Liu, Yan Cheng · 发表于：Translational Pediatrics · 年份：2024 · DOI：10.21037/tp-24-128 · 被引用次数：9 · 研究领域：Gut microbiota and health、Gastrointestinal motility and disorders、Clostridium difficile and Clostridium perfringens research

Background: Early enteral nutrition and the gut microbiota profoundly influence neonatal brain development, with short-chain fatty acids (SCFAs) from the microbiota playing a pivotal role. Understanding the relationship between dysbiosis, SCFAs, and brain development is crucial. In this study, we investigated the impact of antibiotics on the concentration of SCFAs in neonatal feces. Additionally, we developed a model of gut dysbiosis in neonatal mice to examine the potential relationship between this imbalance, SCFAs production, and brain function development. Methods: We measured the SCFAs content in the feces of two groups of neonates, categorized based on whether antibiotics were used, and conducted the Neonatal Behavioral Neurological Assessment (NBNA) test on all neonates. Then we evaluated fecal SCFAs levels in neonates and neonatal mice post-antibiotic treatment using liquid chromatography-mass spectrometry (LC-MS) analysis. Morris water maze (MWM) tests assessed behavioral performance, and western blot analysis examined brain tissue-related proteins-neuron-specific enolase (NSE), ionized calcium binding adaptor molecule-1 (IBA1), and myelin basic proteins (MBP). Results: The use of antibiotics did not affect the NBNA scores of the two groups of neonates, but it did reduce the SCFAs content in their feces. Antibiotic administration induced gut dysbiosis in mice, resulting in decreased IBA1 and MBP expression. Interventions to restore gut microbiota ameliorated these ef...