PMID- 36369946 OWN - NLM STAT- MEDLINE DCOM- 20221115 LR - 20221222 IS - 1949-0984 (Electronic) IS - 1949-0976 (Print) IS - 1949-0976 (Linking) VI - 14 IP - 1 DP - 2022 Jan-Dec TI - Kidney microbiota dysbiosis contributes to the development of hypertension. PG - 2143220 LID - 10.1080/19490976.2022.2143220 [doi] LID - 2143220 AB - Gut microbiota dysbiosis promotes metabolic syndromes (e.g., hypertension); however, the patterns that drive hypertensive pathology and could be targeted for therapeutic intervention are unclear. We hypothesized that gut microbes might translocate to the kidney to trigger hypertension. We aimed to uncover their method of colonization, and thereby how to maintain blood pressure homeostasis. Using combined approaches based on fluorescence in situ hybridization (FISH) and immunofluorescence staining, electron microscopy analysis, bacterial cultures, species identification, and RNA-sequencing-based meta-transcriptomics, we first demonstrated the presence of bacteria within the kidney of spontaneously hypertensive rats (SHRs) and its normotensive counterpart, Wistar-Kyoto rats (WKYs), and patients with hypertension. Translocated renal bacteria were coated with secretory IgA (sIgA) or remained dormant in the L-form. Klebsiella pneumoniae (K.pn) was identified in the kidneys of germ-free (GF) mice following intestinal transplantation, which suggested an influx of gut bacteria into the kidneys. Renal bacterial taxa and their function are associated with hypertension. Hypertensive hosts showed increased richness in the pathobionts of their kidneys, which were partly derived from the gastrointestinal tract. We also demonstrated the indispensable role of bacterial IgA proteases in the translocation of live microbes. Furthermore, Tartary buckwheat dietary intervention reduced blood pressure and modulated the core renal flora-host ecosystem to near-normal states. Taken together, the unique patterns of viable and dormant bacteria in the kidney provide insight into the pathogenesis of non-communicable chronic diseases and cardiometabolic diseases (e.g., hypertension), and may lead to potential novel microbiota-targeted dietary therapies. FAU - Liu, Xin-Yu AU - Liu XY AD - State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China. FAU - Li, Jing AU - Li J AD - Hypertension Center, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. AD - Heart Center & Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China. FAU - Zhang, Yamei AU - Zhang Y AD - Clinical Genetics Laboratory, Affiliated Hospital &Clinical Medical College of Chengdu University, Chengdu, P.R. China. AD - School of Food and Biological Engineering, Chengdu University, Chengdu, China. FAU - Fan, Luyun AU - Fan L AD - Hypertension Center, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. FAU - Xia, Yanli AU - Xia Y AD - Clinical Genetics Laboratory, Affiliated Hospital &Clinical Medical College of Chengdu University, Chengdu, P.R. China. AD - School of Food and Biological Engineering, Chengdu University, Chengdu, China. FAU - Wu, Yongyang AU - Wu Y AD - Department of Urology, Affiliated Sanming First Hospital, Fujian Medical University, Sanming, China. FAU - Chen, Junru AU - Chen J AD - Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, China. FAU - Zhao, Xinyu AU - Zhao X AD - State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China. FAU - Gao, Qiannan AU - Gao Q AD - Hypertension Center, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. FAU - Xu, Bing AU - Xu B AD - Department of Proctology, University of Chinese Academy of Sciences-Shenzhen Hospital (Guang Ming), Shenzhen, China. FAU - Nie, Chunlai AU - Nie C AD - State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China. FAU - Li, Zhengyu AU - Li Z AD - Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China. FAU - Tong, Aiping AU - Tong A AD - State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China. FAU - Wang, Wenjie AU - Wang W AD - Hypertension Center, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. FAU - Cai, Jun AU - Cai J AD - Hypertension Center, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Gut Microbes JT - Gut microbes JID - 101495343 SB - IM MH - Rats MH - Mice MH - Animals MH - Dysbiosis/microbiology MH - *Gastrointestinal Microbiome MH - In Situ Hybridization, Fluorescence MH - Rats, Inbred WKY MH - *Hypertension/etiology MH - *Microbiota/physiology MH - Kidney/metabolism MH - Bacteria/genetics PMC - PMC9662196 OTO - NOTNLM OT - Gut microbiota translocation OT - IgA protease OT - L-form bacteria OT - bacterial translocation OT - cell-wall-deficient bacteria OT - dietary intervention OT - hypertension OT - kidney microbiota OT - sIgA-coated bacteria COIS- No potential conflict of interest was reported by the author(s). EDAT- 2022/11/13 06:00 MHDA- 2022/11/16 06:00 PMCR- 2022/11/12 CRDT- 2022/11/12 03:43 PHST- 2022/11/12 03:43 [entrez] PHST- 2022/11/13 06:00 [pubmed] PHST- 2022/11/16 06:00 [medline] PHST- 2022/11/12 00:00 [pmc-release] AID - 2143220 [pii] AID - 10.1080/19490976.2022.2143220 [doi] PST - ppublish SO - Gut Microbes. 2022 Jan-Dec;14(1):2143220. doi: 10.1080/19490976.2022.2143220.