The Gut and Blood Microbiome in IgA Nephropathy and Healthy Controls

Abstract

Background: IgA nephropathy (IgAN) has been associated with gut dysbiosis, intestinal membrane disruption and translocation of bacteria into blood. Our study aimed to understand the association of gut and blood microbiomes in IgAN patients in relation to healthy controls. Methods: We conducted a case control study with 20 progressive IgAN patients matched with 20 healthy controls, analyzing bacterial DNA quantitatively in blood by 16S PCR and qualitatively in blood and stool by 16S metagenomic sequencing. Between group comparisons as well as comparisons between the blood and gut microbiomes were conducted. Results: Higher median 16S bacterial DNA in blood was found in the IgAN group compared to the healthy controls group (7410 vs 6030 16SrDNA copies/uL blood, p = 0.04). Alpha and beta diversity in both blood and stool was largely similar between the IgAN and healthy groups.. Higher proportions of class Coriobacteriia, and species of genera legionella, Enhydrobacter and parabacteroides in blood; and species of genera Bacteroides, Escherichia-Shigella and some Ruminococcus in stool were observed in IgAN patients in comparison with healthy controls. Taxa distribution were markedly different between the blood and stool samples of each subject in both IgAN and healthy groups without any significant correlation between corresponding gut and blood phyla. Conclusions: Important bacterial taxonomic differences quantitatively in blood and qualitatively in both blood and stool samples detected between IgAN and healthy groups warrant further investigation into their roles in the pathogenesis of IgAN. While gut bacterial translocation into blood may be one of the potential sources of the blood microbiome, marked taxonomic differences between gut and blood samples in each subject in both groups confirms that the blood microbiome does not directly reflect the gut microbiome. Further research is needed into other possible sites of origin and internal regulation of the blood microbiome.

Identification of the composition, stability, and origin of blood microbiome in humans

“…This has been con rmed in the case of various gastrointestinal and other diseases in which intestinal permeability has been altered [4,42,43]. At the same time, Shah et al later found that the blood microbiome does not directly re ect the gut microbiome [43]. Our study con rms this observation as the beta diversity analysis shows that there is a much larger distance between blood and faecal samples than between blood and skin samples, suggesting that the blood microbiome of healthy individuals may originate from the skin microbiome, which partly coincides with Whittle et al results [6].…”

“…It is considered that microorganisms enter the circulation from different body parts, such as the gut [36]. This has been con rmed in the case of various gastrointestinal and other diseases in which intestinal permeability has been altered [4,42,43]. At the same time, Shah et al later found that the blood microbiome does not directly re ect the gut microbiome [43].…”

Faecal Microbiota Transplantation and Chronic Kidney Disease

“…A study on 29 Chinese patients with immunoglobulin A nephropathy (IgAN) also showed a reduced amount of Clostridia, Eubacterium, and Alistipes compared with healthy controls, indicating the pathogenic role of depletion of SCFA-producing bacteria in systemic inflammation and IgAN progression [53]. In patients with IgAN, a higher abundance of class Coriobacteriia and genera Legionella, Enhydrobacter, and Parabacteroides was present in the blood, and genera Bacteroides, Escherichia-Shigella, and Ruminococcus in stool in comparison with healthy controls [51]. Additionally, a clinical study in ESKD patients identified six taxa, including Akkermansia, Dialester, Enterococcus, Rominicoccus, Blautia, and Bacteroides, that contributed to the elevated levels of uraemic toxins [57].…”

The Gut and Kidney Crosstalk in Immunoglobulin A Nephropathy

“…In comparison with healthy controls patients with IgAN had higher proportions of the species of the genera Bacteroides, Escherichia-Shigella, and some Ruminococcus. 72 Another study that analyzed fecal gut microbiota in 52 Chinese patients with IgAN and 25 healthy controls found abundance of Bacteroides compared to healthy controls. 73 The study also highlighted that gut microbial modifications may be associated with the clinical severity of IgAN, pointing that patients with higher urine red blood cell counts or proteinuria levels had a higher percentage of Escherichia-Shigella and a lower percentage of Bifidobacterium.…”