Comprehensive Analysis of Fecal Microbiome and Metabolomics in Hepatic Fibrosis Rats Reveal Hepatoprotective Effects of Yinchen Wuling Powder From the Host-Microbial Metabolic Axis

Abstract

Hepatic fibrosis (HF) is a typical consequence in the development of multiple chronic liver diseases, which is intimately related to the composition and metabolic status of gut microbiota. A myriad of evidence has indicated that traditional Chinese medicine can treat HF by regulating gut microbiota. Yinchen Wuling powder (YCWLP) is a famous traditional Chinese medicine prescription, which has been used to relieve liver diseases for thousands of years. YCWLP has demonstrated protective function on HF, but its effect on the alterations of gut microbiota is still unclear, and its explicit therapeutic mechanism also needs to be further elucidated. In this study, 16S rRNA gene sequencing and fecal metabolomics analysis were combined to investigate the influence of YCWLP on gut microbiota in HF rats and the interactions between gut microbiota and host metabolism. The results showed that YCWLP treatment significantly improved the disorder of multiple organ indices, HF-related cytokines and plasma LPS induced by HF. Masson’s trichrome stainings also showed that YCWLP treatment could significantly alleviate the severity of HF in rats. Additionally, YCWLP could reverse the significant changes in the abundance of certain genera closely related to HF phenotype, including Barnesiella [Ruminococcus] and Christensenella. Meanwhile, YCWLP significantly increased the abundance of Bifidobacterium, Coprococcus and Anaerostipes, which are closely related to butyrate production. Metabolomics and Spearman’s correlation analysis showed that YCWLP could regulate the disorder of arginine biosynthesis, sphingolipid metabolism and alanine, aspartate and glutamate metabolism in HF rats, and these regulations were intimately related to Barnesiella, [Ruminococcus], Christensenella, Coprococcus and Anaerostipes. By explaining the biological significance of the above results, we concluded that YCWLP might ameliorate HF by regulating the imbalance of gut microbiota, increasing the abundance of butyrate-producing bacteria to reduce ammonia production, promote ammonia degradation, and regulate pro-inflammatory cytokines and immune function.

Revealing the Mechanism of Huazhi Rougan Granule in the Treatment of Nonalcoholic Fatty Liver Through Intestinal Flora Based on 16S rRNA, Metagenomic Sequencing and Network Pharmacology

“…The composition of HRG is Yinchen (YC), Juemingzi (JMZ), Dahuang (DH), Zexie (ZX), Zhuling (ZL), Shanzha (SZ), Cangzhu (CZ), Baizhu (BZ), Chenpi (CP), Gualou (GL), Nvzhenzi (NZZ), Mohanlian (MHL), Gouqizi (GQZ), Xiaoji (XJ), Chaihu (CH), Gancao (GC). Studies have shown that this formula can not only improve lipid deposition in the liver, protect liver cell membranes and reduce liver damage but also protect the intestinal barrier and regulate intestinal flora ( Niu et al, 2011 ; Chen et al, 2015 ; Gao et al, 2021 ; Zhang et al, 2021 ; Zhang et al, 2021 ).…”

Combining fecal microbiome and metabolomics to reveal the disturbance of gut microbiota in liver injury and the therapeutic mechanism of shaoyao gancao decoction

“…Pseudo germ-free (PGF) rats were established by giving broad-spectrum antibiotics to explore whether SGD can treat the liver injury by regulating gut microbiotas. Broad-spectrum antibiotics contain cefadroxil (100 mg/kg), neomycin sulfate (300 mg/kg) and erythromycin (300 mg/kg) ( Zhang et al, 2021a ).…”

“…Meanwhile, other groups were given the same amount of water. Record the weight of rats every week ( Zhang et al, 2021a ).…”

Integrated traditional Chinese and Western medicine in the prevention and treatment of non-alcoholic fatty liver disease: future directions and strategies

“…Ingredient modifications of these formulas were performed based on clinically specific symptoms: Ginger pinellia and Bamboo shavings are added for Jaundice; Polygonum cuspidatum is added for those trapped by damp-evil. Yinchen Wuling Powder shows hepatoprotective effects by regulating the imbalance of the gut microbiota and increasing the abundance of butyrate-producing bacteria to regulate pro-inflammatory cytokines and immune function [ 148 ].…”