The intestinal microbiota has been associated with host immunity as well as psoriasis;however,the mechanism of intestinal microbiota regulating psoriasis needs to be demonstrated systematically.Here,we sought to exami...The intestinal microbiota has been associated with host immunity as well as psoriasis;however,the mechanism of intestinal microbiota regulating psoriasis needs to be demonstrated systematically.Here,we sought to examine its role and mechanism of action in the pathogenesis of psoriasis.We found that the severity of psoriasis-like skin phenotype was accompanied by changes in the composition of the intestinal microbiota.We performed co-housing and fecal microbial transplantation(FMT)experiments using the K14-VEGF transgenic mouse model of psoriasis and demonstrated that the transfer of intestinal microbiota from mice with severe psoriasis-like skin phenotype exacerbated psoriasiform skin inflammation in mice with mild symptoms,including increasing the infiltration and differentiation of Th17,and increased the abundance of Prevotella,while decreasing that of Parabacteroides distasonis,in the colon.These alterations affected fatty acid metabolism,increasing the abundance of oleic and stearic acids.Meanwhile,gentamicin treatment significantly reduced the abundance of Prevotella and alleviated the psoriasis-like symptoms in both K14-VEGF mice and imiquimod(IMQ)-induced psoriasis-like mice.Indeed,administration of oleic and stearic acids exacerbated psoriasis-like symptoms and increased Th17 and monocyte-derived dendritic cell infiltration in the skin lesion areas in vivo,as well as increased the secretion of IL-23 by stimulating DCs in vitro.At last,we found that,treatment of PDE-4 inhibitor alleviated psoriasis-like phenotype of K14-VEGF mice accompanied by the recovery of intestinal microbiota,including the decrease of Prevotella and increase of Parabacteroides distasonis.Overall,our findings reveal that the intestinal microbiota modulates host metabolism and psoriasis-like skin inflammation in mice,suggesting a new target for the clinical diagnosis and treatment of psoriasis.展开更多
In recent decades,the global prevalence of metabolic syndrome has surged,posing a significant public health challenge.Metabolic disorders,encompassing diabetes,obesity,nonalcoholic fatty liver disease,and polycystic o...In recent decades,the global prevalence of metabolic syndrome has surged,posing a significant public health challenge.Metabolic disorders,encompassing diabetes,obesity,nonalcoholic fatty liver disease,and polycystic ovarian syndrome,have been linked to alterations in the gut microbiota.Nonetheless,the connection between gut microbiota and host metabolic diseases warrants further investigation.In this review,we delve into the associations between various metabolic disorders and the gut microbiota,focusing on immune responses and bile acid(BA)metabolism.Notably,T helper cells,innate lymphoid cells,macrophages,and dendritic cells have been shown to modulate host metabolism through interactions with intestinal microorganisms and the release of cytokines.Furthermore,secondary BA metabolites,derived from the microbiota,are involved in the pathogenesis of metabolic diseases via the farnesoid X receptor and Takeda G protein-coupled receptor 5.By covering both aspects of this immune system-microorganism axis,we present a comprehensive overview of the roles played by the gut microbiota,microbiota-derived BA metabolites,and immune responses in metabolic diseases,as well as the interplay between these systems.展开更多
基金This work was supported by the National Natural Science Foundation of China(81673061,31271483,81472650,81573050,31872739,30300313)National Science and Technology Major Project(2019ZX09201003-003,2018ZX09733001-001-006,2013ZX09301304001-003,2012ZX10002006-003-001,2009ZX09103-714)+1 种基金Applied Basic Research Program of Sichuan Province(2008SZ0093)Key Research and Development Program of Sichuan Province(2020YFS0271),and the Sichuan Provincial Outstanding Youth Fund(2015JQ0025).
文摘The intestinal microbiota has been associated with host immunity as well as psoriasis;however,the mechanism of intestinal microbiota regulating psoriasis needs to be demonstrated systematically.Here,we sought to examine its role and mechanism of action in the pathogenesis of psoriasis.We found that the severity of psoriasis-like skin phenotype was accompanied by changes in the composition of the intestinal microbiota.We performed co-housing and fecal microbial transplantation(FMT)experiments using the K14-VEGF transgenic mouse model of psoriasis and demonstrated that the transfer of intestinal microbiota from mice with severe psoriasis-like skin phenotype exacerbated psoriasiform skin inflammation in mice with mild symptoms,including increasing the infiltration and differentiation of Th17,and increased the abundance of Prevotella,while decreasing that of Parabacteroides distasonis,in the colon.These alterations affected fatty acid metabolism,increasing the abundance of oleic and stearic acids.Meanwhile,gentamicin treatment significantly reduced the abundance of Prevotella and alleviated the psoriasis-like symptoms in both K14-VEGF mice and imiquimod(IMQ)-induced psoriasis-like mice.Indeed,administration of oleic and stearic acids exacerbated psoriasis-like symptoms and increased Th17 and monocyte-derived dendritic cell infiltration in the skin lesion areas in vivo,as well as increased the secretion of IL-23 by stimulating DCs in vitro.At last,we found that,treatment of PDE-4 inhibitor alleviated psoriasis-like phenotype of K14-VEGF mice accompanied by the recovery of intestinal microbiota,including the decrease of Prevotella and increase of Parabacteroides distasonis.Overall,our findings reveal that the intestinal microbiota modulates host metabolism and psoriasis-like skin inflammation in mice,suggesting a new target for the clinical diagnosis and treatment of psoriasis.
基金This work was supported by the National Natural Science Foundation of China(82130022 and 31925021).
文摘In recent decades,the global prevalence of metabolic syndrome has surged,posing a significant public health challenge.Metabolic disorders,encompassing diabetes,obesity,nonalcoholic fatty liver disease,and polycystic ovarian syndrome,have been linked to alterations in the gut microbiota.Nonetheless,the connection between gut microbiota and host metabolic diseases warrants further investigation.In this review,we delve into the associations between various metabolic disorders and the gut microbiota,focusing on immune responses and bile acid(BA)metabolism.Notably,T helper cells,innate lymphoid cells,macrophages,and dendritic cells have been shown to modulate host metabolism through interactions with intestinal microorganisms and the release of cytokines.Furthermore,secondary BA metabolites,derived from the microbiota,are involved in the pathogenesis of metabolic diseases via the farnesoid X receptor and Takeda G protein-coupled receptor 5.By covering both aspects of this immune system-microorganism axis,we present a comprehensive overview of the roles played by the gut microbiota,microbiota-derived BA metabolites,and immune responses in metabolic diseases,as well as the interplay between these systems.