Jiangtang Decoction Ameliorates Diabetic Kidney Disease Through the Modulation of the Gut Microbiota

Abstract

Jinni Hong,1,2 Tingting Fu,1,2 Weizhen Liu,1,2 Yu Du,1,2 Junmin Bu,1,2 Guojian Wei,1,2 Miao Yu,1,2 Yanshan Lin,1,2 Cunyun Min,1,2 Datao Lin3 1Department of Traditional Chinese Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, 510080, People’s Republic of China; 2Guangdong Provincial Institute of Geriatric, Guangzhou, Guangdong, 510080, People’s Republic of China; 3Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 510080, People’s Republic of ChinaCorrespondence: Jinni HongDepartment of Traditional Chinese Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, 510080, People’s Republic of China, Tel [phone], Fax [phone], Email [email protected] LinDepartment of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 510080, People’s Republic of China, Tel [phone], Fax [phone], Email [email protected]: This study aimed to elucidate the impact of Jiangtang decoction (JTD) on diabetic kidney disease (DKD) and its association with alterations in the gut microbiota.Methods: Using a diabetic mouse model (KK-Ay mice), daily administration of JTD for eight weeks was undertaken. Weekly measurements of body weight and blood glucose were performed, while kidney function, uremic toxins, inflammation factors, and fecal microbiota composition were assessed upon sacrifice. Ultra-structural analysis of kidney tissue was conducted to observe the pathological changes.Results: The study findings demonstrated that JTD improve metabolism, kidney function, uremic toxins and inflammation, while also exerting a modulatory effect on the gut microbiota. Specifically, the genera Rikenella, Lachnoclostridium, and unclassified_c_Bacilli exhibited significantly increased abundance following JTD treatment, accompanied by reduced abundance of norank_f_Lachnospiraceae compared to the model group. Importantly, Rikenella and unclassified_c_Bacilli demonstrated negative correlations with urine protein levels. Lachnoclostridium and norank_f_Lachnospiraceae were positively associated with creatinine (Cr), indoxyl sulfate (IS) and interleukin (IL)-6. Moreover, norank_f_Lachnospiraceae exhibited positive associations with various indicators of DKD severity, including weight, blood glucose, urea nitrogen (UN), kidney injury molecule-1 (KIM-1) levels, trimethylamine-N-oxide (TMAO), p-cresyl sulfate (pCS), nucleotide-binding oligomerization domain (Nod)-like receptor family pyrin domain-containing 3 (NLRP3) and IL-17A production.Conclusion: These findings suggested that JTD possess the ability to modulate the abundance of Rikenella, Lachnoclostridium, unclassified_c_Bacilli and norank_f_Lachnospiraceae within the gut microbiota. This modulation, in turn, influenced metabolic processes, kidney function, uremic toxin accumulation, and inflammation, ultimately contributing to the amelioration of DKD.Graphical Abstract: Keywords: Chinese herbal medicine, gut microbiota, diabetic kidney disease, inflammation, uremic toxins

Keywords

• chinese herbal medicine
• gut microbiota
• diabetic kidney disease
• inflammation
• uremic toxins.