OGG1 deficiency alters the intestinal microbiome and increases intestinal inflammation in a mouse model

OGG1-deficient (Ogg1-/-) animals display increased propensity to age-induced and diet-induced metabolic diseases, including insulin resistance and fatty liver. Since the intestinal microbiome is increasingly understood to play a role in modulating host metabolic responses, we examined gut microbial composition in Ogg1-/- mice subjected to different nutritional challenges. Interestingly, Ogg1-/- mice had a markedly altered intestinal microbiome under both control-fed and hypercaloric diet conditions. Several microbial species that were increased in Ogg1-/- animals were associated with increased energy harvest, consistent with their propensity to high-fat diet induced weight gain. In addition, several pro-inflammatory microbes were increased in Ogg1-/- mice. Consistent with this observation, Ogg1-/- mice were significantly more sensitive to intestinal inflammation induced by acute exposure to dextran sulfate sodium. Taken together, these data indicate that in addition to their proclivity to obesity and metabolic disease, Ogg1-/- mice are prone to colonic inflammation. Further, these data point to alterations in the intestinal microbiome as potential mediators of the metabolic and intestinal inflammatory response in Ogg1-/- mice.OGG1缺陷型（Ogg1-/-）动物的衰老诱导及饮食诱导代谢疾病易感性显著升高，涵盖胰岛素抵抗与脂肪肝两类病症。鉴于肠道菌群在调控宿主代谢应答中的作用日益受到学界重视，本研究对接受不同营养干预的Ogg1-/-小鼠的肠道菌群组成展开了系统分析。值得注意的是，无论在正常喂养还是高热量饮食条件下，Ogg1-/-小鼠的肠道菌群组成均发生显著改变。部分在Ogg1-/-动物中丰度升高的微生物类群与能量摄取增强相关，这与其高脂饮食诱导体重增加的易感性相符。此外，Ogg1-/-小鼠体内的促炎性微生物类群丰度亦有所提升。与该观察结果一致，Ogg1-/-小鼠对急性暴露于葡聚糖硫酸钠（dextran sulfate sodium, DSS）诱导的肠道炎症的敏感性显著升高。综合上述实验数据，本研究表明，除易患肥胖与代谢疾病外，Ogg1-/-小鼠还易于发生结肠炎症。此外，本研究数据提示，肠道菌群组成改变可能是Ogg1-/-小鼠代谢与肠道炎症应答的潜在介导因素。