Zengye Decoction Attenuated Severe Acute Pancreatitis Complicated with Acute Kidney Injury by Modulating the Gut Microbiome and Serum Amino Acid Metabolome

Abstract

Objective. To explore the effect and underlying mechanism of Zengye decoction (ZYD), a traditional formula from China, on the severe acute pancreatitis (SAP) rat model with acute kidney injury (AKI). Methods. The SAP-AKI model was induced by 3.5% sodium taurocholate. Rats were treated with normal saline or ZYD twice and sacrificed at 36 h after modeling. Amylase, lipase, creatinine, blood urea nitrogen, kidney injury molecule 1(KIM-1), and multiple organs’ pathological examinations were used to assess the protective effect of ZYD. Gut microbiome detected by 16S rRNA sequencing analysis and serum amino acid metabolome analyzed by liquid chromatography-mass spectrometry explained the underlying mechanism. The Spearman correlation analysis presented the relationship between microflora and metabolites. Results. ZYD significantly decreased KIM-1( P < 0.05 ) and the pathological score of the pancreas ( P < 0.05 ), colon ( P < 0.05 ), and kidney ( P < 0.05 ). Meanwhile, ZYD shifted the overall gut microbial structure (β-diversity, ANOSIM R = 0.14, P = 0.025 ) and altered the microbial compositions. Notably, ZYD reduced the potentially pathogenic bacteria—Bacteroidetes, Clostridiales vadin BB60 group, and uncultured_Clostridiales_bacterium, but promoted the short-chain fatty acid (SCFA) producers—Erysipelotrichaceae, Bifidobacterium, Lactobacillus, and Moryella (all P < 0.05 ). Moreover, principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), and hierarchical clustering analysis (HCA) presented a remarkable change in amino acid metabolome after SAP-AKI induction and an apparent regulation by ZYD treatment (R2Y 0.878, P = 0.01 ; Q2 0.531, P = 0.01 ). Spearman’s correlation analysis suggested that gut bacteria likely influenced serum metabolites levels (absolute r > 0.4 and FDR P < 0.02 ). Conclusions. ZYD attenuated SAP-AKI by modulating the gut microbiome and serum amino acid metabolome, which may be a promising adjuvant treatment.

Gut Microbiota and Neonatal Acute Kidney Injury

“…A traditional Chinese formula, Zengye decoction, attenuates AKI associated with severe acute pancreatitis in rats by modulating gut microbiota 103 . Moreover, fecal microbiota transplant from donor mice treated with the Chinese medicine formula Qiong-Yu-Gao attenuated cisplatin-induced AKI in recipient mice 104 , suggesting that FMT may be an alternative treatment option for AKI.…”

“…A traditional Chinese formula, Zengye decoction, attenuates AKI associated with severe acute pancreatitis in rats by modulating gut microbiota. 102 Moreover, fecal microbiota transplant from donor mice treated with the Chinese medicine formula Qiong-Yu-Gao attenuated cisplatin-induced AKI in recipient mice, 103 suggesting that FMT may be an alternative treatment option for AKI. FMT may reduce the accumulation of uremic toxins in subjects with AKI, 104 as the microbial cocktail isolated from feces reduced urea and creatinine concentrations in a mice model of AKI.…”

Xiebai Zengye decoction improves respiratory function and attenuates inflammation in juvenile rats with postinfection cough via regulating ERK signaling pathway

“…Research suggests that Zengye decoction can improve metabolic disorders such as diabetes. 11,12 The extracellular signal-regulated kinase (ERK) signaling pathway plays a crucial role in transmitting signals from the cell surface to the nucleus in the body. It interacts with other transduction pathways, forming a complex regulatory network that governs various cellular functions.…”

“…Zengye decoction, a combination of Scrophulariae (Xuanshen), Ophiopogonis (Maidong), and Rehmannia (Shengdi), is widely used in many Asian countries. Research suggests that Zengye decoction can improve metabolic disorders such as diabetes 11,12 …”