Integrated Fecal Microbiome and Serum Metabolomics Analysis Reveals Abnormal Changes in Rats with Immunoglobulin A Nephropathy and the Intervention Effect of Zhen Wu Tang

Abstract

Immunoglobulin A nephropathy (IgAN), an autoimmune renal disease with complicated pathogenesis, is one of the principal reasons for end-stage renal disease in the clinic. Evidence has linked apparent alterations in the components of the microbiome and metabolome to renal disease in rats. However, thus far, there is insufficient evidence that supports the potential relationship between gut microbiome, circulating metabolites, and IgAN. This study was designed to probe the effects of IgAN on intestinal microecology and metabolic phenotypes and to understand the possible underlying mechanisms. Fecal and serum samples were collected from IgAN rats. Composition of the gut microbiota and biochemical changes in the metabolites was analyzed using 16S rDNA sequencing and untargeted metabolomics. The IgAN rats exhibited renal insufficiency and increased concentration of 24-h urine protein, in addition to deposition of IgA and IgG immune complexes in the kidney tissues. There was a disturbance in the balance of gut microbiota in IgAN rats, which was remarkably associated with renal damage. Marked changes in microbial structure and function were accompanied by apparent alterations in 1,403 serum metabolites, associated with the disorder of energy, carbohydrate, and nucleotide metabolisms. Administration of Zhen Wu Tang ameliorated microbial dysbiosis and attenuated the renal damage. Besides, treatment with Zhen Wu Tang modulated the metabolic phenotype perturbation in case of gut microbiota dysbiosis in IgAN rats. In conclusion, these findings provided a comprehensive understanding of the potential relationship between the intestinal microbiota and metabolic phenotypes in rats with IgAN. Elucidation of the intestinal microbiota composition and metabolic signature alterations could identify predictive biomarkers for disease diagnosis and progression, which might contribute to providing therapeutic strategies for IgAN.

Recent Advances in Clinical Diagnosis and Pharmacotherapy Options of Membranous Nephropathy

“…The combination of chemical drugs and Yinxingdamo injection and chemical drugs and Danhong injection had the potential to be the best Chinese herbal injections relative to total clinical effectiveness, serum albumin, and 24-h urinary protein excretion. Moreover, Li et al (2020b ) and Li et al (2020c ) demonstrated that Zhen-Wu-Tang could ameliorate immunoglobulin A nephropathy in rats.…”

Gut Microbes in Immunoglobulin A Nephropathy and Their Potential Therapeutic Applications

“…These biomarkers of metabolites were mainly involved in lipid metabolism, signal transduction, carbohydrate metabolism, amino acid metabolism, and biosynthesis of other secondary metabolites ( 29 ). They may be a core metabolite of IgAN and may be an important mediator between intestinal and blood circulation ( 46 ).…”

“…Feeding of Zhen Wu Tang to IgAN model rats significantly changed the gut microbiota with increased the relative abundance of microbial species at the family level, including Peptostreptococcaceae and Family_XIII while suppressing the abundances of Cyanobacteria and Proteobacteria . Moreover, the model group had higher abundance of Lachnospiraceae, Lactobacillaceae, Erysipelotrichaceae , and Bacteroidaceae relative to the normal group; ZWT intervention reduced these levels ( 46 ). Zhen Wu Tang can improve the microecological imbalance and reduce kidney damage in IgAN rats ( 46 ).…”

“…Moreover, the model group had higher abundance of Lachnospiraceae, Lactobacillaceae, Erysipelotrichaceae , and Bacteroidaceae relative to the normal group; ZWT intervention reduced these levels ( 46 ). Zhen Wu Tang can improve the microecological imbalance and reduce kidney damage in IgAN rats ( 46 ).…”

Mechanisms of Zhenwu decoction for the treatment of renal fibrosis at various stages: What is the role of Corynebacterium?

“…Consequently, a close interconnection has been proposed between the gut and kidney, which is known as the gut–kidney axis ( Khoury et al, 2017 ; Chen et al, 2019 ). The association between fecal microbiome and serum metabolomics in IgA nephropathy rats and the intervention effect of ZWD have been reported ( Li et al, 2021 ). However, whether ZWD attenuates renal fibrosis through modifying the gut microbiota remains to be elucidated.…”