Accumulated evidence suggested that gut microbial dysbiosis interplayed with progressive chronic kidney disease(CKD).However,no available therapy is effective in suppressing progressive CKD.Here,using microbiomics in ...Accumulated evidence suggested that gut microbial dysbiosis interplayed with progressive chronic kidney disease(CKD).However,no available therapy is effective in suppressing progressive CKD.Here,using microbiomics in 480 participants including healthy controls and patients with stage 1–5 CKD,we identified an elongation taxonomic chain Bacilli-Lactobacillales-Lactobacillaceae-Lactobacillus-Lactobacillus johnsonii correlated with patients with CKD progression,whose abundance strongly correlated with clinical kidney markers.L.johnsonii abundance reduced with progressive CKD in rats with adenine-induced CKD.L.johnsonii supplementation ameliorated kidney lesion.Serum indole-3-aldehyde(IAld),whose level strongly negatively correlated with creatinine level in CKD rats,decreased in serum of rats induced using unilateral ureteral obstruction(UUO)and 5/6 nephrectomy(NX)as well as late CKD patients.Treatment with IAld dampened kidney lesion through suppressing aryl hydrocarbon receptor(AHR)signal in rats with CKD or UUO,and in cultured 1-hydroxypyrene-induced HK-2 cells.Renoprotective effect of IAld was partially diminished in AHR deficiency mice and HK-2 cells.Our further data showed that treatment with L.johnsonii attenuated kidney lesion by suppressing AHR signal via increasing serum IAld level.Taken together,targeting L.johnsonii might reverse patients with CKD.This study provides a deeper understanding of how microbial-produced tryptophan metabolism affects host disease and discovers potential pathways for prophylactic and therapeutic treatments for CKD patients.展开更多
Mutational signatures refer to distinct patterns of DNA mutations that occur in a specific context or under certain conditions.It is a powerful tool to describe cancer etiology.We conducted a study to show cancer hete...Mutational signatures refer to distinct patterns of DNA mutations that occur in a specific context or under certain conditions.It is a powerful tool to describe cancer etiology.We conducted a study to show cancer heterogeneity and cancer specificity from the aspect of mutational signatures through collinearity analysis and machine learning techniques.Through thorough training and independent validation,our results show that while the majority of the mutational signatures are distinct,similarities between certain mutational signature pairs can be observed through both mutation patterns and mutational signature abundance.The observation can potentially assist to determine the etiology of yet elusive mutational signatures.Further analysis using machine learning approaches demonstrated moderate mutational signature cancer specificity.Skin cancer among all cancer types demonstrated the strongest mutational signature specificity.展开更多
基金supported by National Natural Science Foundation of China(Nos.82074002,82274079,82274192,32100631)Shaanxi Key Science and Technology Plan Project(No.2023-ZDLSF-26)+3 种基金Macao Young Scholars Program(No.AM2023024)China Postdoctoral Science Foundation(No.2023T160061)Capital’s Funds for Health Improvement and Research(No.2024-4-40215)Natural Science Foundation of Zhejiang Province(No.LZ22H280001).
文摘Accumulated evidence suggested that gut microbial dysbiosis interplayed with progressive chronic kidney disease(CKD).However,no available therapy is effective in suppressing progressive CKD.Here,using microbiomics in 480 participants including healthy controls and patients with stage 1–5 CKD,we identified an elongation taxonomic chain Bacilli-Lactobacillales-Lactobacillaceae-Lactobacillus-Lactobacillus johnsonii correlated with patients with CKD progression,whose abundance strongly correlated with clinical kidney markers.L.johnsonii abundance reduced with progressive CKD in rats with adenine-induced CKD.L.johnsonii supplementation ameliorated kidney lesion.Serum indole-3-aldehyde(IAld),whose level strongly negatively correlated with creatinine level in CKD rats,decreased in serum of rats induced using unilateral ureteral obstruction(UUO)and 5/6 nephrectomy(NX)as well as late CKD patients.Treatment with IAld dampened kidney lesion through suppressing aryl hydrocarbon receptor(AHR)signal in rats with CKD or UUO,and in cultured 1-hydroxypyrene-induced HK-2 cells.Renoprotective effect of IAld was partially diminished in AHR deficiency mice and HK-2 cells.Our further data showed that treatment with L.johnsonii attenuated kidney lesion by suppressing AHR signal via increasing serum IAld level.Taken together,targeting L.johnsonii might reverse patients with CKD.This study provides a deeper understanding of how microbial-produced tryptophan metabolism affects host disease and discovers potential pathways for prophylactic and therapeutic treatments for CKD patients.
基金Division of Cancer Prevention,National Cancer Institute,Grant/Award Number:P30CA240139。
文摘Mutational signatures refer to distinct patterns of DNA mutations that occur in a specific context or under certain conditions.It is a powerful tool to describe cancer etiology.We conducted a study to show cancer heterogeneity and cancer specificity from the aspect of mutational signatures through collinearity analysis and machine learning techniques.Through thorough training and independent validation,our results show that while the majority of the mutational signatures are distinct,similarities between certain mutational signature pairs can be observed through both mutation patterns and mutational signature abundance.The observation can potentially assist to determine the etiology of yet elusive mutational signatures.Further analysis using machine learning approaches demonstrated moderate mutational signature cancer specificity.Skin cancer among all cancer types demonstrated the strongest mutational signature specificity.
