Gars Aviva, Ronczkowski Nicole M, Chassaing Benoit, Castillo-Ruiz Alexandra, Forger Nancy G
Neuroscience Institute, Georgia State University, Atlanta, GA, United States.
INSERM U1016, Team "Mucosal Microbiota in Chronic Inflammatory Diseases", CNRS UMR 8104, Université de Paris, Paris, France.
Front Cell Neurosci. 2021 Jun 8;15:682505. doi: 10.3389/fncel.2021.682505. eCollection 2021.
The microbiota plays important roles in host metabolism and immunity, and its disruption affects adult brain physiology and behavior. Although such findings have been attributed to altered neurodevelopment, few studies have actually examined microbiota effects on the developing brain. This review focuses on developmental effects of the earliest exposure to microbes. At birth, the mammalian fetus enters a world teeming with microbes which colonize all body sites in contact with the environment. Bacteria reach the gut within a few hours of birth and cause a measurable response in the intestinal epithelium. In adults, the gut microbiota signals to the brain via the vagus nerve, bacterial metabolites, hormones, and immune signaling, and work in perinatal rodents is beginning to elucidate which of these signaling pathways herald the very first encounter with gut microbes in the neonate. Neural effects of the microbiota during the first few days of life include changes in neuronal cell death, microglia, and brain cytokine levels. In addition to these effects of direct exposure of the newborn to microbes, accumulating evidence points to a role for the maternal microbiota in affecting brain development via bacterial molecules and metabolites while the offspring is still . Hence, perturbations to microbial exposure perinatally, such as through C-section delivery or antibiotic treatment, alter microbiota colonization and may have long-term neural consequences. The perinatal period is critical for brain development and a close look at microbiota effects during this time promises to reveal the earliest, most primary effects of the microbiota on neurodevelopment.
微生物群在宿主代谢和免疫中发挥着重要作用,其破坏会影响成人大脑的生理和行为。尽管这些发现被归因于神经发育的改变,但实际上很少有研究考察微生物群对发育中大脑的影响。本综述聚焦于最早接触微生物的发育影响。出生时,哺乳动物胎儿进入一个充满微生物的世界,这些微生物会定殖于所有与外界接触的身体部位。细菌在出生后数小时内进入肠道,并在肠上皮引发可测量的反应。在成年人中,肠道微生物群通过迷走神经、细菌代谢产物、激素和免疫信号向大脑发送信号,围产期啮齿动物的研究开始阐明这些信号通路中哪些预示着新生儿首次接触肠道微生物。生命最初几天微生物群的神经影响包括神经元细胞死亡、小胶质细胞和脑内细胞因子水平的变化。除了新生儿直接接触微生物的这些影响外,越来越多的证据表明,母体微生物群在后代仍处于发育阶段时,通过细菌分子和代谢产物对大脑发育具有影响作用。因此,围产期微生物接触的扰动,如剖宫产或抗生素治疗,会改变微生物群的定殖,并可能产生长期的神经后果。围产期对大脑发育至关重要,仔细研究这一时期微生物群的影响有望揭示微生物群对神经发育最早、最主要的影响。