Table_2_Fecal microbiota transplantation unveils sex-specific differences in a controlled cortical impact injury mouse model.XLSX

IntroductionContusion type of traumatic brain injury (TBI) is a major cause of locomotor disability and mortality worldwide. While post-TBI deleterious consequences are influenced by gender and gut dysbiosis, the sex-specific importance of commensal gut microbiota is underexplored after TBI. In this study, we investigated the impact of controlled cortical impact (CCI) injury on gut microbiota signature in a sex-specific manner in mice.
MethodsWe depleted the gut microflora of male and female C57BL/6 mice using antibiotic treatment. Thereafter, male mice were colonized by the gut microbiota of female mice and vice versa, employing the fecal microbiota transplantation (FMT) method. CCI surgery was executed using a stereotaxic impactor (Impact One™). For the 16S rRNA gene amplicon study, fecal boli of mice were collected at 3 days post-CCI (dpi).
Results and discussionCCI-operated male and female mice exhibited a significant alteration in the genera of Akkermansia, Alistipes, Bacteroides, Clostridium, Lactobacillus, Prevotella, and Ruminococcus. At the species level, less abundance of Lactobacillus helveticus and Lactobacillus hamsteri was observed in female mice, implicating the importance of sex-specific bacteriotherapy in CCI-induced neurological deficits. FMT from female donor mice to male mice displayed an increase in genera of Alistipes, Lactobacillus, and Ruminococcus and species of Bacteroides acidifaciens and Ruminococcus gnavus. Female FMT-recipient mice from male donors showed an upsurge in the genus Lactobacillus and species of Lactobacillus helveticus, Lactobacillus hamsteri, and Prevotella copri. These results suggest that the post-CCI neurological complications may be influenced by the differential gut microbiota perturbation in male and female mice.

引言 脑挫伤型创伤性脑损伤（traumatic brain injury, TBI）是全球范围内运动功能障碍与死亡的主要诱因。尽管创伤性脑损伤后的不良预后受性别与肠道菌群失调（gut dysbiosis）的影响，但创伤性脑损伤后共生肠道菌群（commensal gut microbiota）的性别特异性作用仍未得到充分探索。本研究以小鼠为模型，探究了控制性皮层撞击（controlled cortical impact, CCI）损伤对肠道菌群特征的性别特异性影响。
方法 本研究通过抗生素处理清除雄性与雌性C57BL/6小鼠的肠道菌群。随后采用粪便菌群移植（fecal microbiota transplantation, FMT）技术，将雌性小鼠的肠道菌群定植于雄性小鼠体内，反之亦然。控制性皮层撞击手术使用立体定位撞击仪（Impact One™）实施。针对16S rRNA基因扩增子测序研究，我们在创伤后3天（dpi）收集小鼠的粪便颗粒。
结果与讨论 接受控制性皮层撞击手术的雄性与雌性小鼠，其阿克曼菌属（Akkermansia）、Alistipes、拟杆菌属（Bacteroides）、梭菌属（Clostridium）、乳杆菌属（Lactobacillus）、普雷沃菌属（Prevotella）以及瘤胃球菌属（Ruminococcus）的菌群丰度均发生显著改变。在物种水平上，雌性小鼠的瑞士乳杆菌（Lactobacillus helveticus）与仓鼠乳杆菌（Lactobacillus hamsteri）丰度更低，这提示针对性别特异性的菌群疗法在改善控制性皮层撞击诱导的神经功能缺损中具有重要价值。将雌性供体小鼠的粪便菌群移植给雄性受体小鼠后，受体小鼠的Alistipes、乳杆菌属与瘤胃球菌属丰度显著升高，产酸拟杆菌（Bacteroides acidifaciens）与格氏瘤胃球菌（Ruminococcus gnavus）的丰度亦有所增加。而接受雄性供体小鼠粪便菌群移植的雌性受体小鼠，其乳杆菌属丰度显著升高，瑞士乳杆菌、仓鼠乳杆菌与柯氏普雷沃菌（Prevotella copri）的丰度同样上升。上述结果表明，创伤性脑损伤后的神经并发症可能受雌雄小鼠肠道菌群紊乱差异的影响。