Dysbiosis in the Salivary Microbiome Associated with IgA Nephropathy—‍A‍ ‍Japanese Cohort Study

Abstract

IgA nephropathy is one of the leading causes of chronic kidney disease in Japan. Since the origin and mechanisms by which IgA nephropathy develops currently remain unclear, a confirmed disease diagnosis is currently only possible by highly invasive renal biopsy. With the background of the salivary microbiome as a rich source of biomarkers for systemic diseases, we herein primarily aimed to investigate the salivary microbiome as a tool for the non-invasive diagnosis of IgA nephropathy. In a comparison of salivary microbiome profiles using 16S rRNA amplicon sequencing, significant differences were observed in microbial diversity and richness between IgA nephropathy patients and healthy controls. Furthermore, recent studies reported that patients with IgA nephropathy are more likely to develop inflammatory bowel diseases and that chronic inflammation of the tonsils triggered the recurrence of IgA nephropathy. Therefore, we compared the salivary microbiome of IgA nephropathy patients with chronic tonsillitis and ulcerative colitis patients. By combining the genera selected by the random forest algorithm, we were able to distinguish IgA nephropathy from healthy controls with an area under the curve (AUC) of 0.90, from the ulcerative colitis group with AUC of 0.88, and from the chronic tonsillitis group with AUC of 0.70. Additionally, the genus Neisseria was common among the selected genera that facilitated the separation of the IgA nephropathy group from healthy controls and the chronic tonsillitis group. The present results indicate the potential of the salivary microbiome as a biomarker for the non-invasive diagnosis of IgA nephropathy.

Impact of oral microbiota on pathophysiology of GVHD

“…Dysbiosis in saliva microbiome has been identified in the patient group, with more Neisseria spp. than in the healthy group ( 115 ). An association with preterm delivery has also been noted ( 116 ).…”

Findings on the Relationship Between Intestinal Microbiome and Vasculitis

“…The oral microbiome may also play a potential role in the pathogenesis of IgAN with seven predictive functional profiles, including glycosphingolipid biosynthesis, oxidative phosphorylation, and N-glycan biosynthesis ( He et al., 2021b ). The salivary microbiome can be a potential biomarker for IgA nephropathy, as proved in the Japanese population ( Khasnobish et al., 2021 ).…”

Current understanding of IgA antibodies in the pathogenesis of IgA nephropathy

“…Since mucosal IgA are generated by commensal bacteria, it is conceivable that certain bacteria are involved in Gd-IgA1 production. Although several intestinal or oral bacteria have been reported to affect clinical parameters in patients with IgAN ( 35 , 36 ), specific bacteria directly involved in Gd-IgA1 production have not been identified. Instead, several types of toll-like receptor (TLR), a family of pattern recognition receptors that recognize pathogen-associated molecular patterns and play a central role in sensing microbial infection, have been reported to be involved in the pathogenesis of IgAN ( 24 ).…”