Foley Kelly A, MacFabe Derrick F, Vaz Alisha, Ossenkopp Klaus-Peter, Kavaliers Martin
Graduate Program in Neuroscience, The University of Western Ontario, London, ON N6A 5B7, Canada; Department of Psychology, The University of Western Ontario, London, ON N6A 5C2, Canada.
Department of Psychology, The University of Western Ontario, London, ON N6A 5C2, Canada; The Kilee Patchell-Evans Autism Research Group, Departments of Psychology and Psychiatry, Division of Developmental Disabilities, The University of Western Ontario, London, ON N6A 5C2, Canada.
Int J Dev Neurosci. 2014 Dec;39:68-78. doi: 10.1016/j.ijdevneu.2014.04.001. Epub 2014 Apr 18.
Emerging evidence suggests that the gut microbiome plays an important role in immune functioning, behavioral regulation and neurodevelopment. Altered microbiome composition, including altered short chain fatty acids, and/or immune system dysfunction, may contribute to neurodevelopmental disorders such as autism spectrum disorders (ASD), with some children with ASD exhibiting both abnormal gut bacterial metabolite composition and immune system dysfunction. This study describes the effects of prenatal propionic acid (PPA), a short chain fatty acid and metabolic product of many antibiotic resistant enteric bacteria, and of prenatal lipopolysaccharide (LPS), a bacterial mimetic and microbiome component, on social behavior in male and female neonatal, adolescent and adult rats. Pregnant Long-Evans rats were injected once a day with either a low level of PPA (500 mg/kg SC) on gestation days G12-16, LPS (50 μg/kg SC) on G12, or vehicle control on G12 or G12-16. Sex- and age-specific, subtle effects on behavior were observed. Both male and female PPA treated pups were impaired in a test of their nest seeking response, suggesting impairment in olfactory-mediated neonatal social recognition. As well, adolescent males, born to PPA treated dams, approached a novel object more than control animals and showed increased levels of locomotor activity compared to prenatal PPA females. Prenatal LPS produced subtle impairments in social behavior in adult male and female rats. These findings raise the possibility that brief prenatal exposure to elevated levels of microbiome products, such as PPA or LPS, can subtly influence neonatal, adolescent and adult social behavior.
新出现的证据表明，肠道微生物群在免疫功能、行为调节和神经发育中发挥着重要作用。微生物群组成的改变，包括短链脂肪酸的改变和/或免疫系统功能障碍，可能导致神经发育障碍，如自闭症谱系障碍（ASD），一些患有ASD的儿童同时表现出肠道细菌代谢产物组成异常和免疫系统功能障碍。本研究描述了产前丙酸（PPA，一种短链脂肪酸和许多耐抗生素肠道细菌的代谢产物）和产前脂多糖（LPS，一种细菌模拟物和微生物群成分）对雄性和雌性新生、青少年和成年大鼠社会行为的影响。怀孕的Long-Evans大鼠在妊娠第12 - 16天每天注射一次低剂量的PPA（500 mg/kg皮下注射），在第12天注射LPS（50 μg/kg皮下注射），或在第12天或第12 - 16天注射载体对照。观察到了对行为的性别和年龄特异性的细微影响。接受PPA治疗的雄性和雌性幼崽在寻找巢穴反应测试中均受损，这表明嗅觉介导的新生社会识别受损。此外，由接受PPA治疗的母鼠所生的青春期雄性大鼠比对照动物更接近新物体，并且与产前接受PPA治疗的雌性大鼠相比，其运动活动水平增加。产前LPS对成年雄性和雌性大鼠的社会行为产生了细微的损害。这些发现增加了一种可能性，即产前短暂暴露于高水平的微生物群产物，如PPA或LPS，可能会微妙地影响新生儿、青少年和成年期的社会行为。
