皮肤的光老化,慢性疾病,会产生皮肤的外观变化和癌变。因此,探讨其发病机制和探索有效的治疗方法具有重要意义。肠道菌群和肠道代谢在多种疾病中具有关键作用。然而,它们在皮肤光老化中的作用没有得到很好的测试。在目前的工作中,结果表明,与对照组相比,MDA的水平,SOD和CAT与氧化应激有关,COLI的水平,CER,和与皮肤功能相关的HA,和IL-1β的mRNA水平,与炎症相关的IL-6、TNF-α在长期暴露于紫外线照射后小鼠均有显著改变。皮肤病理组织也严重受损。AQP3和FLG的卵白质程度显著下降。紫外线照射还通过激活TNFR1/TRAF2介导的MAPK通路促进皮肤光老化,其中P38/P-P38,c-FOS/P-c-FOS,与对照组相比,模型小鼠的MMP1,TNFR1和TRAF2明显增加。在粪便微生物移植(FMT)实验中,我们发现对照组小鼠的肠道微生物组通过调节P38/P-P38、c-FOS/P-c-FOS的蛋白水平来缓解皮肤光老化,MMP1、TNFR1和TRAF2。16SrRNA测序发现,发现1639个肠道细菌,其中包括norank_f_Ruminoccaceae在内的15种细菌,Lachnosirac-eae_NK4A136_组,衣原体,等。,在属水平上显着不同。非靶向GC-TOF/MS和UHPLC-MS/MS代谢组学显示包括牛磺酸在内的72种和188种代谢产物,鸟氨酸,L-精氨酸,L-组氨酸,蔗糖与对照组相比差异显著。然后,氨基酸靶向检测显示10种氨基酸,包括L-鸟氨酸,对照组L-精氨酸和L-瓜氨酸水平高于模型组。此外,我们还发现,衣原体丰度的变化可能通过调节L-精氨酸代谢来影响皮肤光老化。一些肠道细菌和代谢产物包括氨基酸可能与皮肤光老化密切相关,这将为将来治疗皮肤光老化提供新的方法。
Photoaging of skin, a chronic disease, can produce the appearance changes and cancer lesions of skin. Therefore, it is of great significance to investigate the mechanisms and explore effective methods to treat the disorder. Gut microbiota and intestinal metabolisms have critical roles in a variety of diseases. However, their roles on photoaging of skin were not well tested. In the present work, the results showed that compared with control group, the levels of MDA, SOD and CAT associated with oxidative stress, the levels of COL I, CER, and HA associated with skin function, and the mRNA levels of IL-1β, IL-6, TNF-α associated with inflammation after long-term exposure to ultraviolet radiation in mice were significantly changed. Skin pathological tissue was also seriously damaged. The protein levels of AQP3 and FLG were significantly decreased. Ultraviolet exposure also promoted skin photoaging by activating TNFR1/TRAF2-mediated MAPK pathway, in which the protein levels of P38/P-P38, c-FOS/P-c-FOS, MMP1, TNFR1 and TRAF2 were significantly increased in model mice compared with control group. In fecal microbiota transplantation (FMT) experiment, we found that the intestinal microbiome of control mice alleviated skin photoaging via adjusting the protein levels of P38/P-P38, c-FOS/P-c-FOS, MMP1, TNFR1 and TRAF2. 16S rRNA sequencing found that 1639 intestinal bacteria were found, in which 15 bacteria including norank_f_Ruminococcaceae, Lachnospirac -eae_NK4A136_group, Lachnoclostridium, etc., were significantly different at the genus level. Untargeted GC-TOF/MS and UHPLC-MS/MS metabolomics showed 72 and 188 metabolites including taurine, ornithine, L-arginine, L-histidine, sucrose with significant differences compared with control group. Then, amino acid targeting assay showed 10 amino acids including L-ornithine, L-arginine and L-citrulline with higher levels in control group compared with model group. In addition, we also found that the variation of Lachnoclostridium abundance may regulate L-arginine metabolism to affect skin photoaging. Some intestinal bacteria and metabolites including amino acids may be closely related to skin photoaging, which should provide new methods to treat skin photoaging in the future.