Sex differences associate with late microbiome alterations after murine surgical sepsis.
Sex differences associate with late microbiome alterations after murine surgical sepsis.
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DOI：
10.1097/ta.0000000000003599
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发表时间：
2022-08-01
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我们假设败血症后雌性小鼠与雄性小鼠的微生物区系有差异。在腹部感染后14天，女性表现出不同的微生物区系。这种恢复上的差异可能在脓毒症后不同性别之间的预后差异中起作用。脓毒症引起的肠道微生物群改变导致败血症相关的发病率和死亡率。有证据表明，与男性相比，女性败血症后的结局有所改善，我们假设女性小鼠与男性相比，保持了微生物区系的弹性。采用盲肠结扎穿孔(CLP)加抗生素、生理盐水复苏和每日慢性应激的混合性别C57BL/6小鼠，并与未感染/不使用抗生素的对照组进行比较。在这项工作中，对幼龄(3-5月龄)和老年(18-22月龄)成年小鼠的结果进行了性别、独立和依赖年龄的分析。分别于第7天和第14天处死小鼠，对粪便细菌DNA进行16S rRNA基因测序。分别用香农指数和布雷-柯蒂斯主坐标法测定α和β多样性。实施了错误发现率(FDR)校正，以考虑潜在的住房影响。在对照组小鼠中，雄性和雌性小鼠之间的α或β多样性没有差异(FDR值分别为0.76和0.99)。然而，与基线相比，接受每日慢性应激的接受CLP的雄性小鼠在CLP后7天微生物区系α多样性下降(Shannon FDR，0.005)，并持续到CLP后14天(Shannon FDR，0.001)。此外，与对照组相比，雄性小鼠即使在第14天也保持了β多样性的差异(FDR，<；0.0001)。相比之下，雌性小鼠在CLP后7天微生物区系α多样性(香农FDR，0.03)和β多样性(FDR，0.02)降低，但到CLP后第14天，它们的α和β多样性(分别为香农FDR0.5和FDR0.02)恢复。对雌性的进一步分析表明，只有年轻的雌性小鼠在CLP后第14天与对照组没有不同(β多样性)。虽然败血症引起的肠道微生物区系紊乱最初发生在雄性和雌性C57BL/6小鼠身上，但雌性小鼠在第14天表现出不同的微生物群。这可能主要见于较年轻的雌性小鼠。这种恢复上的差异可能在脓毒症后不同性别之间的预后差异中起作用。
We hypothesized that female mice had differences (vs males) in their microbiota after sepsis. Females demonstrated different microbiota 14 days after abdominal sepsis. This difference in recovery may play a role in outcome differences between sexes after sepsis. Sepsis-induced gut microbiome alterations contribute to sepsis-related morbidity and mortality. Given evidence for improved postsepsis outcomes in females compared with males, we hypothesized that female mice maintain microbiota resilience versus males. Mixed-sex C57BL/6 mice underwent cecal ligation and puncture (CLP) with antibiotics, saline resuscitation, and daily chronic stress and were compared with naive (nonsepsis/no antibiotics) controls. For this work, the results of young (3–5 months) and old (18–22 months) adult mice were analyzed by sex, independent and dependent of age. Mice were sacrificed at days 7 and 14, and 16S rRNA gene sequencing was performed on fecal bacterial DNA. α and β diversity were determined by Shannon index and Bray-Curtis with principal coordinate analysis, respectively. False discovery rate (FDR) correction was implemented to account for potential housing effect. In control mice, there was no difference in α or β diversity between male and female mice (FDR, 0.76 and 0.99, respectively). However, male mice that underwent CLP with daily chronic stress had a decrease in microbiota α diversity at 7 days post-CLP (Shannon FDR, 0.005), which was sustained at 14 days post-CLP (Shannon FDR, 0.001), compared with baseline. In addition, male mice maintained differences in β diversity even at day 14 compared with controls (FDR, <0.0001). In contrast, female mice had a decreased microbiota α diversity (Shannon FDR, 0.03) and β diversity (FDR, 0.02) 7 days post-CLP but recovered their α and β diversity by post-CLP day 14 (Shannon FDR, 0.5, and FDR, 0.02, respectively). Further analysis of females revealed that only young female mice were not different (β diversity) post-CLP day 14 to controls. Although sepsis-induced perturbations of the intestinal microbiota occur initially in both male and female C57BL/6 mice, females demonstrate different microbiota by day 14. This may be seen primarily in younger females. This difference in recovery may play a role in outcome differences between sexes after sepsis.