Understanding the Gut-Kidney Axis in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: An Analysis of Gut Microbiota Composition

Abstract

Increasing evidence suggested that gut microbiota played critical roles in developing autoimmune diseases. This study investigated the correlation between gut microbiota and antineutrophil cytoplasmic antibody-associated vasculitis (AAV) with kidney injury. We analyzed the fecal samples of 23 AAV patients with kidney injury using a 16s RNA microbial profiling approach. The alpha-diversity indexes were significantly lower in AAV patients with kidney injury than healthy controls (Sobs P < 0.001, Shannon P < 0.001, Chao P < 0.001). The beta-diversity difference demonstrated a significant difference among AAV patients with kidney injury, patients with lupus nephritis (LN), and health controls (ANOSIM, p = 0.001). Among these AAV patients, the Deltaproteobacteria, unclassified_o_Bacteroidales, Prevotellaceae, Desulfovibrionaceae Paraprevotella, and Lachnospiraceae_NK4A136_group were correlated negatively with serum creatinine, and the proportion of Deltaproteobacteria, unclassified_o_Bacteroidales, Desulfovibrionaceae, Paraprevotella, and Lachnospiraceae_NK4A136_group had a positive correlation with eGFR. In conclusion, the richness and diversity of gut microbiota were reduced in AAV patients with kidney injury, and the alteration of gut microbiota might be related with the severity of kidney injury of AAV patients. Targeted regulation of gut microbiota disorder might be a potential treatment for AAV patients with kidney injury.

Causal relationship in gut microbiota and upper urinary urolithiasis using Mendelian randomization

“…Oscillospira, a genus capable of synthesizing short-chain fatty acids like butyrate, has been linked to inflammation-related disorders, such as inflammatory bowel disease, non-alcoholic fatty liver disease, and aging processes distinguished through increased levels of circulating inflammatory mediators (Chierico et al, 2017 ; Lima and Longman, 2021 ; Xu et al, 2021 ), and is strongly negatively associated with pro-inflammatory monocyte chemoattractant protein-1 (Buford, 2017 ). Deltaproteobacteria were found to be negatively related to antineutrophil cytoplasmic antibody-associated vasculitis (AAV) with kidney injury (Yu et al, 2022 ). The herbal tea ingredient Rabdosia serra acts as an anti-inflammatory agent by boosting the number of helpful bacteria, such as Lactobacillus, as well as reducing the number of harmful bacteria including Eubacterium xylanophilum , thus alleviating artificially induced colitis in mice (Li et al, 2022 ).…”

Findings on the Relationship Between Intestinal Microbiome and Vasculitis

“…They also established a random forest model algorithm based on operational taxonomic unit (OUT) markers for the diagnosis and prediction of disease activity in MPA, which showed good predictive power (Yu et al, 2021). Another study also reported a gut-kidney axis in AAV, showing that changes in gut microbiota composition are associated with the degree of renal injury in AAV patients; this suggested that targeted regulation of gut dysbiosis may be a new intervention to reduce kidney damage in AAV patients (Yu et al, 2022).…”

“…Culturing these mice in a germ-free condition or with antibiotic treatment can significantly downregulate the Th17 cells and relieve kidney inflammation, while Citrobacter rodentium infection can expand Th17 cells and aggravate kidney damage in mice (Krebs et al, 2016). Some cross-sectional studies have proved that alterations of gut microbiota (including reduced SCFAproducing taxons) existed in AAV and were also linked to kidney injury (Table 2) by analyzing the fecal samples of patients using 16s rRNA sequencing (Najem et al, 2018;Yu et al, 2021;Yu et al, 2022) (Yu et al, 2021). They also established a random forest model algorithm based on operational taxonomic unit (OUT) markers for the diagnosis and prediction of disease activity in MPA, which showed good predictive power (Yu et al, 2021).…”

Intestinal homeostasis in the gut-lung-kidney axis: a prospective therapeutic target in immune-related chronic kidney diseases

“…Gut leaky may cause a series of immune-related diseases, such as systemic lupus erythematosus (SLE) (55) and ANCA-associated vasculitis (AAV) (56).…”