From the Department of Surgery (P.A.E., D.B.D., J.M., L.K., B.F., D.C.N., R.F.U., M.L.D., J.R., F.A.M., S.C.B., L.L.M., A.M.M., R.M.T.), Department of Aging and Geriatric Research (P.A.E., R.T.M., C.L.), Department of Medicine (E.C.L.), and Division of Infectious Diseases and Global Medicine, Department of Neuroscience (T.C.F.), University of Florida College of Medicine, Gainesville; Department of Nutrition and Integrative Physiology (O.L.), Florida State University College of Health and Human Sciences, Tallahassee; Department of Pharmacology and Therapeutics (G.C.), College of Medicine, and Department of Molecular Genetics and Microbiology (R.M.T.), University of Florida; and Section of General Surgery (R.M.T.); North Florida/South Georgia Veterans Health System, Gainesville, Florida.
J Trauma Acute Care Surg. 2022 Aug 1;93(2):137-146. doi: 10.1097/TA.0000000000003599. Epub 2022 Mar 24.
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.
脓毒症引起的肠道微生物组改变导致与脓毒症相关的发病率和死亡率。鉴于与男性相比，女性在脓毒症后有更好的预后，我们假设女性小鼠相对于男性小鼠维持肠道微生物组的恢复能力。
混合性别 C57BL/6 小鼠接受盲肠结扎和穿刺（CLP）加抗生素、盐水复苏，并每日接受慢性应激，与未感染（非脓毒症/无抗生素）对照相比。在此项工作中，通过性别、独立于年龄和依赖于年龄分析年轻（3-5 个月）和老年（18-22 个月）成年小鼠的结果。在第 7 天和第 14 天处死小鼠，对粪便细菌 DNA 进行 16S rRNA 基因测序。通过 Shannon 指数和 Bray-Curtis 主坐标分析分别确定 α 和 β 多样性。实施错误发现率（FDR）校正以考虑潜在的住房效应。
在对照小鼠中，雌雄小鼠的 α 或 β 多样性无差异（FDR，分别为 0.76 和 0.99）。然而，接受 CLP 加每日慢性应激的雄性小鼠在 CLP 后 7 天的肠道微生物组 α 多样性下降（Shannon FDR，0.005），在 CLP 后 14 天持续下降（Shannon FDR，0.001），与基线相比。此外，即使在第 14 天，雄性小鼠的β 多样性仍与对照组有差异（FDR，<0.0001）。相比之下，雌性小鼠在 CLP 后 7 天的肠道微生物组 α 多样性降低（Shannon FDR，0.03）和β 多样性降低（FDR，0.02），但在 CLP 后 14 天恢复了其 α 和β 多样性（Shannon FDR，0.5 和 FDR，0.02，分别）。对雌性小鼠的进一步分析显示，只有年轻的雌性小鼠在 CLP 后 14 天与对照组的β 多样性没有差异。
尽管脓毒症引起的肠道微生物组的改变最初在 C57BL/6 雌雄小鼠中都有发生，但在第 14 天，雌性小鼠的肠道微生物组表现出不同的特征。这种差异主要见于年轻的雌性小鼠。这种恢复能力的差异可能在脓毒症后性别间结局的差异中起作用。
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