Exploration Of The Anti-photoaging Mechanism Of Limosilactobacillus Fermentum By Skin Microbiome

With the growing demand for healthy skin,skin photoaging has attracted more and more attention.Since the launch of the Human Microbiome Project,the importance of microorganisms in skin health has been thoroughly analyzed.At present,probiotics are widely used to improve skin health,especially to alleviate photoaging,and have become a new hotspot of scientific research and market application,but the specific mechanisms and the active anti-photoaging metabolites are still unclear.In this thesis,the anti-photoaging mechanisms of Lactobacillus were jointly analyzed by means of multiomics:Firstly,the micro-ecological characteristics and potential mechanism of skin photoaging were analyzed by establishing an observation cohort of long-term unilateral sun exposure and establishing a photoaging animal model.Then,according to the key microorganisms damaged in photoaging,the study targeted and screened the strains with the function of preventing and controlling photoaging from the resource bank of healthy functional microorganisms from China.On this basis,the study explored the active metabolites of Limosilactobacillus fermentum against UVA(ultraviolet radiation A)-induced epidermal photoaging,by combining comparative genomics and targeted metabolomics.At the same time,the study analyzed the effects of Limosilactobacillus fermentum UVB Active metabolites and molecular pathways in dermal photoaging by means of combining transcriptomics and non-targeted metabolomics.This research lays a solid foundation for the creation of a series of efficient and safe methods of anti-photoaging.The main results obtained are as follows:(1)According to the observation cohort and experimental animal model,the analysis of 16S r RNA amplicon sequencing showed that long-term light exposure significantly reduced the relative abundance of Lactobacillus in the epidermis and dermis.Through the prediction of microbial function and the correlation analysis of environmental factors,it was found that the changes of skin microbes after long-term light exposure can cause the reduction of microbial-derived anti-aging factors such as Ecotin and nicotinamide mononucleotide transporter,leading to the diminished function of the skin to repair photodamage and the increased expression of metalloproteinases and inflammatory factors in skin cells,suggesting that maintaining skin microecological balance is conducive to preventing skin wrinkles and inflammation.These series of results suggest that maintaining the microecological balance of the skin after light exposure is beneficial to prevent aging symptoms such as skin wrinkles.(2)According to the key skin micro-ecological characteristics damaged in photoaging,Limosilactobacillus fermentum XJC60,a high-efficiency antioxidant strain with repairing effect on UVB-damaged epidermis,was obtained by targeted screening in the resource bank of healthy functional microorganisms from China.The comparative genome and targeted metabolome analysis were combined and found that the anti-photoaging metabolites of XJC60 is nicotinamide.With high content of nicotinamide,XJC60 can stabilize NAD~+/NADH levels in skin after UV-damage,restore mitochondrial membrane potential level and reduce skin intracellular ROS levels.Then,the study then verified that the fermentation supernatant of XJC60 can effectively inhibit the degradation of skin collagen and inflammation after UVB damage in vivo and in vitro.(3)According to the key skin microecological characteristics damaged in the photoaging process,Limosilactobacillus fermentum XJC48,a probiotic with the effect of repairing UVA-damaged dermal cells,was targeted and screened from the resource library of healthy functional microorganisms sourced in China.Non-targeted metabolome analysis showed that the specific unimodal polysaccharide in XJC48metabolite was the key metabolite that exerts its anti-photoaging effect.Besides,transcriptome analysis suggested that the unimodal polysaccharide derived from XJC48can achieve anti-UVA damage effect by regulating the IGF-1/Akt/Fox O pathway.In summary,this thesis discovered that Lactobacillus was the key genus by exploring the skin microbiome mechanism of photoaging,and screens and verifies the anti-photoaging effects of two strains of Limosilactobacillus fermentum XJC60 and XJC48 in vivo and in vitro in the resource bank of healthy functional microorganisms derived from China.This thesis provides a theoretical basis for the creation of a series of efficient and safe anti-photoaging methods.