Department of Surgery, Burn Research and Alcohol Research Programs, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado.
Department of Medicine, Division of Infectious Disease, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado.
Shock. 2023 Oct 1;60(4):585-593. doi: 10.1097/SHK.0000000000002202. Epub 2023 Aug 7.
The Earth's population is aging, and by 2050, one of six people will be 65 years or older. Therefore, proper treatment of injuries that disproportionately impact people of advanced age will be more important. Clinical studies reveal people 65 years or older account for 16.5% of all burn injuries and experience higher morbidity, including neurocognitive decline, and mortality that we and others believe are mediated, in part, by heightened intestinal permeability. Herein, we used our clinically relevant model of scald burn injury in young and aged mice to determine whether age and burn injury cooperate to induce heightened colonic damage, alterations to the fecal microbiome, and whether resultant changes in the microbiome correlate with neuroinflammation. We found that aged, burn-injured mice have an increase in colonic lymphoid aggregates, inflammation, and proinflammatory chemokine expression when compared with young groups and sham-injured aged mice. We then performed fecal microbiota sequencing and found a striking reduction in gut protective bacterial taxa, including Akkermansia , in the aged burn group compared with all other groups. This reduction correlated with an increase in serum fluorescein isothiocyanate-Dextran administered by gavage, indicating heightened intestinal permeability. Furthermore, loss of Akkermansia was highly correlated with increased messenger RNA expression of neuroinflammatory markers in the brain, including chemokine ligand 2, TNF-α, CXC motif ligand 1, and S100 calcium-binding protein A8. Finally, we discovered that postburn alterations in the microbiome correlated with measures of strength in all treatment groups, and those that performed better on the rotarod and hanging wire tests had higher abundance of Akkermansia than those that performed worse. Taken together, these findings indicate that loss of protective bacteria after burn injury in aged mice contributes to alterations in the colon, gut leakiness, neuroinflammation, and strength. Therefore, supplementation of protective bacteria, such as Akkermansia , after burn injury in aged patients may have therapeutic benefit.
人口老龄化，到 2050 年，每六个人中就有一人年满 65 岁。因此，对老年人中比例较高的伤害进行适当的治疗将变得更加重要。临床研究表明，65 岁及以上的人群占所有烧伤患者的 16.5%，他们的发病率更高，包括神经认知能力下降和死亡率，我们和其他人认为这部分是由肠道通透性增加介导的。在这里，我们使用了我们在年轻和老年小鼠中具有临床相关性的烫伤烧伤模型，以确定年龄和烧伤损伤是否共同诱导结肠损伤加剧、粪便微生物组改变，以及微生物组的变化是否与神经炎症相关。我们发现，与年轻组和假损伤老年组相比，老年烧伤组的结肠淋巴样聚集物、炎症和促炎趋化因子表达增加。然后，我们进行了粪便微生物组测序，发现与所有其他组相比，老年烧伤组中保护性肠道细菌的数量明显减少，包括阿克曼菌。这种减少与通过灌胃给予的血清荧光素异硫氰酸酯-葡聚糖的增加相关，表明肠道通透性增加。此外，阿克曼菌的缺失与大脑中神经炎症标志物的信使 RNA 表达增加高度相关，包括趋化因子配体 2、TNF-α、CXC 基序配体 1 和 S100 钙结合蛋白 A8。最后，我们发现烧伤后微生物组的改变与所有治疗组的力量测量相关，在旋转棒和悬挂线测试中表现更好的动物的阿克曼菌丰度高于表现较差的动物。总之，这些发现表明，老年小鼠烧伤后保护性细菌的缺失导致结肠改变、肠道通透性增加、神经炎症和力量下降。因此，在老年烧伤患者中补充保护性细菌，如阿克曼菌，可能具有治疗益处。
