Reduced fecal short-chain fatty acids levels and the relationship with gut microbiota in IgA nephropathy

Abstract

Background: IgA nephropathy(IgAN)) is the common pathological type of glomerular diseases. The role of gut microbiota in mediating "gut-IgA nephropathy" has not received sufficient attention in the previous studies. The purpose of this study was to investigate the changes of fecal short-chain fatty acids(SCFAs), a metabolite of the intestinal microbiota, in patients with IgAN and its correlation with intestinal flora and clinical indicators, and to further investigate the role of the gut-renal axis in IgAN.

Methods: There were 29 patients with IgAN and 29 normal control subjects recruited from January 2018 to May 2018. The fresh feces were collected. The fecal SCFAs were measured by gas chromatography/mass spectrometry and gut microbiota was analysed by16S rDNA sequences, followed by estimation of α- and β-diversity. Correlation analysis was performed using the spearman's correlation test between SCFAs and gut microbiota.

Results: The levels of acetic acid, propionic acid, butyric acid, isobutyric acid and caproic acid in the IgAN patients were significantly reduced compared with control group(P < 0.05). Butyric acid(r=-0.336, P = 0.010) and isobutyric acid(r=-0.298, P = 0.022) were negatively correlated with urea acid; butyric acid(r=-0.316, P = 0.016) was negatively correlated with urea nitrogen; caproic acid(r=-0.415,P = 0.025) showed negative correlation with 24-h urine protein level.Exemplified by the results of α-diversity and β-diversity, the intestinal flora of IgAN patients was significantly different from that of the control group. Acetic acid was positively associated with c_Clostridia(r = 0.357, P = 0.008), o_Clostridiales(r = 0.357, P = 0.008) and g_Eubacterium_coprostanoligenes_group(r = 0.283, P = 0.036). Butyric acid was positively associated with g_Alistipes (r = 0.278, P = 0.040). The relative abundance of those were significantly decreased in IgAN group compared to control group.

Conclusions: The levels of fecal SCFAs in the IgAN patients were reduced, and correlated with clinical parameters and gut microbiota, which may be involved in the pathogenesis of IgAN, and this finding may provide a new therapeutic approach.

Keywords: Gut microbiota; IgA nephropathy; Short-chain fatty acids.

Fig. 1

The gut microbiota composition of IgAN patients was significantly different from that of the control. The α-diversity of the microbiota presented as Chao1 (P = 0.0945, A), observed species (P = 0.051, B), Simpson (P = 0.067, C) and the Shannon index (P = 0.033, D). The β-diversity in the IgAN and control groups was calculated by NMDS (Stress = 0.132) (Fig. 1E)

Fig. 2

Correlations between SCFAs and microbial indexes. The network diagram of the correlation analysis of microbial indexes and SCFAs (A), red represents SCFAs, and green microbial indexes. The color of the edge shows the correlation coefficient (red positive and blue negative)(P < 0.05). The node size represents the centrality, that is, the number of consecutive starting from it. LDA was performed to determine the difference of the SCFAs related microbial taxa in two groups (B). Significantly different bacteria with LDA scores ≥ 2.0 were diagrammed on cladogram