ABSTRACT
Objective:
To study the structure and diversity of
intestinal flora in
IgA nephropathy (IgAN)
patients, and to explore the correlation of intestinal microorganisms with clinical
indicators and renal
pathology.
Methods:
Fifteen IgAN
patients in the First Affiliated
Hospital of Baotou Medical College from May 2020 to September 2020 were retrospectively enrolled as IgAN group, and 8 healthy
families and 7
health checkups were enrolled as healthy
control group. Illumina
high-throughput sequencing technology was performed for
DNA sequencing in the 16S
rDNA-V4 region of all
bacteria in the
feces sample. QIIME 2 was used to process and analyze original sequence, compared with Greengenes (V138) database. The DADA2
software was called to denoise the data, which was equivalent to a 100% similarity cluster (OTU was a 97% similarity cluster). PCoA was used to analyze the structure and diversity of
intestinal flora. Spearman correlation or Pearson correlation
analysis was used to analyze the correlation of differential
flora with renal
pathology and clinical
indicators.
Results:
(1) The intestinal microbial β diversity in IgAN
patients was significantly different from that in healthy controls ( P=0.010). (2) Compared with the healthy
control group, the numbers of
intestinal flora species in IgAN group were significantly increased in 1 phylum, 3
families and 22 genus. At the levels from phylum to
family, the species numbers of
Firmicutes and Ruminococcaceae in IgAN
patients reduced than those in healthy controls and the species numbers of
Chloroflexi, Gaiellaceae,
Staphylococcaceae and
Family-XⅢ in IgAN
patients increased than those in healthy controls (all P<0.05). At the genus level, compared with the healthy controls, the species number of Subdoligranulum in IgAN
patients was significantly reduced ( P=0.020), and the species number of
Ruminococcus- gnavus- group was significantly increased ( P=0.004). (3) At the phylum level of the species number,
Firmicutes in IgAN
patients was positively correlated to
albumin (ALB) ( r=0.637, P=0.037) and
IgG ( r=0.452, P=0.046), Gemmatimonadetes was negatively correlated to
serum creatinine ( r=-0.453, P=0.045),
Verrucomicrobia was negatively correlated to
IgM ( r=-0.450, P=0.046), and Patescibacteria was positively correlated to
IgA ( r=0.469, P=0.037). At the genus level of the species number,
Ruminococcus- gnavus- group ( r=-0.614, P=0.004) and Megamonas ( r=-0.451, P=0.042) were negatively correlated to ALB; Subdoligranulum was positively correlated to ALB ( r=0.563, P=0.009); Dialister was negatively correlated to C3 ( r=-0.427, P=0.041) and was positively correlated to
IgA ( r=0.434, P=0.035);
Veillonella was positively correlated to estimated
glomerular filtration rate ( r=0.452, P=0.043). The species numbers of Eisenbergiella ( r=-0.850, P=0.007), Holdemania ( r=-0.845, P=0.008), Flavonifractor ( r=-0.845, P=0.008), and Ruminiclostridium- 9 ( r=-0.845, P=0.008) were negatively correlated to glomerulosclerosis or adhesion (S) of Oxford
classification; the species number of Fusicatenibacter was negatively correlated to mesangial hypercellularity ( r=-0.845, P=0.008); the number of Coprococcus- 2 was positively correlated to S ( r=0.738, P=0.037) and tubular
atrophy or interstitial
fibrosis ( r=0.756, P=0.030). (4)
Random forest model was built with
Ruminococcus- gnavus- group and Subdoligranulum, after fitting the area under the
receiver operating characteristic curve was 0.927.
Conclusions:
The
intestinal flora of IgAN
patients is different from that in
healthy subjects. Changes of
intestinal flora in IgAN
patients are related to clinical
indicators and renal
pathology. In particular,
Ruminococcus- gnavus- group and Subdoligranulum may
play an important
role in IgAN.