The gut microbiota plays a crucial role in maintaining host health and modulating disease progression.Microbiota-derived metabolites(MDMs)form a complex and diverse repertoire of molecules that interact uniquely with ...The gut microbiota plays a crucial role in maintaining host health and modulating disease progression.Microbiota-derived metabolites(MDMs)form a complex and diverse repertoire of molecules that interact uniquely with the host and regulate epigenetics.In this review,we provide a comprehensive overview by examining the current evidence on how MDMs reshape host epigenetic landscape,and we highlight the innovative concept of the“MDMs-epigenetic(MDME)axis”as a potential framework for exploring and understanding microbiota-host interactions.Next,we underscore the significance of the MDME axis in driving mechanistic studies and elucidating the underlying biological processes and pathophysiological pathways involved in various diseases.Finally,we discuss the impact of MDMs on epigenetic landscapes,outline future directions,and highlight their pivotal role in both mechanistic investigation and the development of clinical therapies.展开更多
Inflammatory bowel diseases(IBDs)are increasingly recognized as a pressing global health concern.The gut microbiome emerges as both a potential therapeutic target and a repository for pharmacological interventions in ...Inflammatory bowel diseases(IBDs)are increasingly recognized as a pressing global health concern.The gut microbiome emerges as both a potential therapeutic target and a repository for pharmacological interventions in IBDs management.This perspective aims to elucidate the pivotal findings from recent studies concerning the anti-inflammatory properties of gut microbiota-derived metabolites(GMDMs),dissect the strengths and challenges of GMDMs as treatment strategies for IBDs,and highlight the integral role of nuclear receptors in mediating the interplay between IBD pathogenesis and GMDMs.Through the integration of these perspectives,our objective is to deepen the understanding of the therapeutic promise of nuclear receptor-targeted GMDMs,thus propelling forward the exploration and formulation of new pharmacological treatments for IBDs.展开更多
Gut microbiota have been reported to play an important role in the occurrence and development of malignant tumors.Currently,clinical studies have identified specific gut microbiota and its metabolites associated with ...Gut microbiota have been reported to play an important role in the occurrence and development of malignant tumors.Currently,clinical studies have identified specific gut microbiota and its metabolites associated with efficacy of immunotherapy in multiple types of cancers.Preclinical investigations have elucidated that gut microbiota modulate the antitumor immunity and affect the efficacy of cancer immunotherapy.Certain microbiota and its metabolites may favorably remodel the tumor microenvironment by engaging innate and/or adaptive immune cells.Understanding how the gut microbiome interacts with cancer immunotherapy opens new avenues for improving treatment strategies.Fecal microbial transplants,probiotics,dietary interventions,and other strategies targeting the microbiota have shown promise in preclinical studies to enhance the immunotherapy.Ongoing clinical trials are evaluating these approaches.This review presents the recent advancements in understanding the dynamic interplay among the host immunity,the microbiome,and cancer immunotherapy,as well as strategies for modulating the microbiome,with a view to translating into clinical applications.展开更多
Both preclinical and established rheumatoid arthritis(RA)patients display alterations in the gut microbiome.Prevotella spp.are preferentially enriched in a subset of RA patients.Here,we isolated a Prevotella strain,P....Both preclinical and established rheumatoid arthritis(RA)patients display alterations in the gut microbiome.Prevotella spp.are preferentially enriched in a subset of RA patients.Here,we isolated a Prevotella strain,P.copri RA,from the feces of RA patients and showed that colonization of P.copri RA exacerbated arthritis in a collagen-induced arthritis(CIA)model.With the presence of P.copri RA colonization,a high-fiber diet exacerbated arthritis via microbial alterations and intestinal inflammation.Colonization of P.copri together with a high-fiber diet enabled the digestion of complex fiber,which led to the overproduction of organic acids,including fumarate,succinate and short-chain fatty acids.Succinate promoted proinflammatory responses in macrophages,and supplementation with succinate exacerbated arthritis in the CIA model.Our findings highlight the importance of dysbiosis when evaluating the effects of dietary interventions on RA pathogenesis and provide new insight into dietary interventions or microbiome modifications to improve RA management.展开更多
基金supported by the National Key Research and Development Program(2022YFA1303900)the National Natural Science Foundation of China(NSFC)(82172288).
文摘The gut microbiota plays a crucial role in maintaining host health and modulating disease progression.Microbiota-derived metabolites(MDMs)form a complex and diverse repertoire of molecules that interact uniquely with the host and regulate epigenetics.In this review,we provide a comprehensive overview by examining the current evidence on how MDMs reshape host epigenetic landscape,and we highlight the innovative concept of the“MDMs-epigenetic(MDME)axis”as a potential framework for exploring and understanding microbiota-host interactions.Next,we underscore the significance of the MDME axis in driving mechanistic studies and elucidating the underlying biological processes and pathophysiological pathways involved in various diseases.Finally,we discuss the impact of MDMs on epigenetic landscapes,outline future directions,and highlight their pivotal role in both mechanistic investigation and the development of clinical therapies.
基金supported by the National Natural Science Foundation of China(82373940&82104238).
文摘Inflammatory bowel diseases(IBDs)are increasingly recognized as a pressing global health concern.The gut microbiome emerges as both a potential therapeutic target and a repository for pharmacological interventions in IBDs management.This perspective aims to elucidate the pivotal findings from recent studies concerning the anti-inflammatory properties of gut microbiota-derived metabolites(GMDMs),dissect the strengths and challenges of GMDMs as treatment strategies for IBDs,and highlight the integral role of nuclear receptors in mediating the interplay between IBD pathogenesis and GMDMs.Through the integration of these perspectives,our objective is to deepen the understanding of the therapeutic promise of nuclear receptor-targeted GMDMs,thus propelling forward the exploration and formulation of new pharmacological treatments for IBDs.
基金supported in part by the National Key Research and Development Program of China(2020YFA0509200)Innovative Research Team of High-Level Local Universities in Shanghai(SSMU-ZLCX20180200)+3 种基金the National Natural Science Foundation of China(82250005,31970718,81830081,81972203)Clinical Research Plan of Shanghai Hospital Development Center(SHDC2020CR1034B)Shanghai Science and Technology Commission(20JC1410100)Shanghai Municipal Health Commission,Collaborative Innovation Cluster Project(2019CXJQ02)。
文摘Gut microbiota have been reported to play an important role in the occurrence and development of malignant tumors.Currently,clinical studies have identified specific gut microbiota and its metabolites associated with efficacy of immunotherapy in multiple types of cancers.Preclinical investigations have elucidated that gut microbiota modulate the antitumor immunity and affect the efficacy of cancer immunotherapy.Certain microbiota and its metabolites may favorably remodel the tumor microenvironment by engaging innate and/or adaptive immune cells.Understanding how the gut microbiome interacts with cancer immunotherapy opens new avenues for improving treatment strategies.Fecal microbial transplants,probiotics,dietary interventions,and other strategies targeting the microbiota have shown promise in preclinical studies to enhance the immunotherapy.Ongoing clinical trials are evaluating these approaches.This review presents the recent advancements in understanding the dynamic interplay among the host immunity,the microbiome,and cancer immunotherapy,as well as strategies for modulating the microbiome,with a view to translating into clinical applications.
基金supported by the National Natural Science Foundation of China (81788101,82230060,81630064,and 81701624)the CAMS Innovation Fund for Medical Sciences (CIFMS) (2021-I2M-1-017,2021-I2M-1-047,2021-I2M-1-040,and 2021-I2M-1-016)+1 种基金the Capital’s Funds for Health Improvement and Research (2020-2-4019)the National Key Research and Development Program of China (Grant no.2018YFE0207300).
文摘Both preclinical and established rheumatoid arthritis(RA)patients display alterations in the gut microbiome.Prevotella spp.are preferentially enriched in a subset of RA patients.Here,we isolated a Prevotella strain,P.copri RA,from the feces of RA patients and showed that colonization of P.copri RA exacerbated arthritis in a collagen-induced arthritis(CIA)model.With the presence of P.copri RA colonization,a high-fiber diet exacerbated arthritis via microbial alterations and intestinal inflammation.Colonization of P.copri together with a high-fiber diet enabled the digestion of complex fiber,which led to the overproduction of organic acids,including fumarate,succinate and short-chain fatty acids.Succinate promoted proinflammatory responses in macrophages,and supplementation with succinate exacerbated arthritis in the CIA model.Our findings highlight the importance of dysbiosis when evaluating the effects of dietary interventions on RA pathogenesis and provide new insight into dietary interventions or microbiome modifications to improve RA management.
