Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland.
Department of Microbiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland.
Int J Mol Sci. 2022 Mar 9;23(6):2964. doi: 10.3390/ijms23062964.
Inflammatory bowel diseases (IBD) are commonly considered as Crohn's disease and ulcerative colitis, but the possibility that the alterations in gut microbiota and oxidative stress may affect the course of experimental colitis in obese physically exercising mice treated with the intestinal alkaline phosphatase (IAP) has been little elucidated. Mice fed a high-fat-diet (HFD) or normal diet (ND) for 14 weeks were randomly assigned to exercise on spinning wheels (SW) for 7 weeks and treated with IAP followed by intrarectal administration of TNBS. The disease activity index (DAI), grip muscle strength test, oxidative stress biomarkers (MDA, SOD, GSH), DNA damage (8-OHdG), the plasma levels of cytokines IL-2, IL-6, IL-10, IL-12p70, IL-17a, TNF-α, MCP-1 and leptin were assessed, and the stool composition of the intestinal microbiota was determined by next generation sequencing (NGS). The TNBS-induced colitis was worsened in obese sedentary mice as manifested by severe colonic damage, an increase in DAI, oxidative stress biomarkers, DNA damage and decreased muscle strength. The longer running distance and weight loss was observed in mice given IAP or subjected to IAP + SW compared to sedentary ones. Less heterogeneous microbial composition was noticed in sedentary obese colitis mice and this effect disappeared in IAP + SW mice. Absence of , lower proportion of , and , an increase in and , a decrease in oxidative stress biomarkers, 8-OHdG content and proinflammatory cytokines were observed in IAP + SW mice. IAP supplementation in combination with moderate physical activity attenuates the severity of murine colitis complicated by obesity through a mechanism involving the downregulation of the intestinal cytokine/chemokine network and oxidative stress, the modulation of the gut microbiota and an improvement of muscle strength.
炎症性肠病（IBD）通常被认为是克罗恩病和溃疡性结肠炎，但肠道微生物群和氧化应激的改变可能会影响肥胖的运动锻炼的小鼠实验性结肠炎的病程，而这种可能性尚未得到充分阐明。用肠道碱性磷酸酶（IAP）处理的高脂肪饮食（HFD）或正常饮食（ND）喂养 14 周的小鼠被随机分为 7 周的旋转轮（SW）运动组，并接受 IAP 治疗，然后直肠内给予 TNBS。评估疾病活动指数（DAI）、握力测试、氧化应激生物标志物（MDA、SOD、GSH）、DNA 损伤（8-OHdG）、细胞因子 IL-2、IL-6、IL-10、IL-12p70、IL-17a、TNF-α、MCP-1 和瘦素的血浆水平，并通过下一代测序（NGS）确定肠道微生物群的粪便组成。肥胖不运动的小鼠中 TNBS 诱导的结肠炎加重，表现为严重的结肠损伤、DAI 增加、氧化应激生物标志物、DNA 损伤和肌肉力量下降。与不运动的小鼠相比，给予 IAP 或进行 IAP+SW 的小鼠跑步距离更长，体重减轻更多。久坐肥胖结肠炎小鼠的微生物组成更不均匀，而 IAP+SW 小鼠的这种影响消失。IAP+SW 小鼠中未检测到 ， 比例较低， 、 和 减少， 和 增加，氧化应激生物标志物、8-OHdG 含量和促炎细胞因子减少。IAP 补充与适度的体育活动相结合，通过下调肠道细胞因子/趋化因子网络和氧化应激、调节肠道微生物群和改善肌肉力量，减轻肥胖合并的小鼠结肠炎的严重程度。
