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Jingqian Zhao,1,2,* Chenyu Zhao,1,3,* Tianrong Xun,1 Xiaokang Wang,1 Sui Wei,1,3 Chunxiao Ye,1 Mimi Zhang,1 Dan Guo,4 Xixiao Yang1 1Department of Pharmacy, Shenzhen Hospital, Southern Medical University, Shenzhen, People’s Republic of China; 2School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, People’s Republic of China; 3School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, People’s Republic of China; 4Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dan Guo; Xixiao Yang, Email nfyyyxb@smu.edu.cn; yaxx@smu.edu.cnPurpose: This study aims to investigate the effects of Huang Gan formula (HGF), a Chinese herbal prescription used for chronic kidney disease (CKD), on the regulation of the gut microbiota and colonic microenvironment of CKD.Methods: CKD rats were induced by 150 mg/kg adenine gavage for 4 weeks, then orally treated with or without 3.6 g/kg or 7.2 g/kg of HGF for 8 weeks. The renal function and structure were analyzed by biochemical detection, hematoxylin and eosin, Masson’s trichrome, Sirius red and immunochemical staining. Average fecal weight and number in the colon were recorded to assess colonic motility. Further, the changes in the gut microbiota and colonic microenvironment were evaluated by 16S rRNA sequencing, RT-PCR or immunofluorescence. The levels of inflammatory cytokines, uremic toxins, and NF-κB signaling pathway were detected by RT-PCR, ELISA, chloramine-T method or Western blotting. Redundancy analysis biplot and Spearman’s rank correlation coefficient were used for correlation analysis.Results: HGF significantly improved renal function and pathological injuries of CKD. HGF could improve gut microbial dysbiosis, protect colonic barrier and promote motility of colonic lumens. Further, HGF inhibited systemic inflammation through a reduction of TNF-α, IL-6, IL-1β, TGF-β 1, and a suppression of NF-κB signaling pathway. The serum levels of the selected uremic toxins were also reduced by HGF treatment. Spearman correlation analysis suggested that high-dose HGF inhibited the overgrowth of bacteria that were positively correlated with inflammatory factors (eg, TNF-α) and uremic toxins (eg, indoxyl sulfate), whereas it promoted the proliferation of bacteria belonging to beneficial microbial groups and was positively correlated with the level of IL-10.Conclusion: Our results suggest that HGF can improve adenine-induced CKD via suppressing systemic inflammation and uremia, which may associate with the regulations of the gut microbiota and colonic microenvironment.Keywords: chronic kidney disease, systemic inflammation, colonic microenvironment, gut-kidney axis |
