Taxonomic and functional shifts of gut microbiome in immunoglobulin A vasculitis children and their mothers

Abstract

Objectives: To examine the gut microbiota characteristics in children with immunoglobulin A vasculitis and their interrelationships with the host, while evaluate the vertical inheritance of microbiota in the development and progression of IgA vasculitis.

Methods: This study investigated the gut microbiome of 127 IgA vasculitis mother-child pairs and 62 matched healthy mother-child pairs, and compared the gut microbial composition of different groups. The pathway enrichment analysis evaluated potential gut microbiome-mediated pathways involved in the pathophysiology of IgA vasculitis. The Spearman correlation analysis illustrated the relationships between clinical variables and bacterial biomarkers.

Results: This study identified distinct intestinal microbiome in IgA vasculitis children compared to healthy children, and further pointed out the association in gut microbiota between IgA vasculitis children's and their mother's. The relative abundance of Megamonas and Lactobacillus in IgAV children was positively correlated with that in their mothers. The pathway enrichment analysis found microbial biosynthesis of vitamins and essential amino acids was upregulated in children with IgA vasculitis. Correlation analysis showed bacterial biomarkers were correlated with indicators of blood coagulation.

Conclusion: Children with IgA vasculitis have unique bacterial biomarkers and may affect coagulation function, and their gut microbiome was closely associated with that of their mothers. The observed association in gut microbiota between IgA vasculitis children and their mothers suggested a potential intergenerational influence of the maternal microbiota on the development or progression of IgA vasculitis in children.

Keywords: bacterial biomarker; gut microbiota; immunoglobulin A vasculitis; microbial pathway; mother-child pairs.

Figure 1

Distinct gut microbiomes were observed in IgAV children (IgAV-C) compared to healthy controls (H-C). (A) Four indexes of α-diversity representing the abundance and evenness of the gut microbiota, in the intestinal microbiome compared between IgAV-C and H-C groups. H-C group was shown in blue and IgAV-C group was shown in red. (B) PCoA and boxplot are shown along the first two principal coordinates of Bray-Curtis distances for IgAV-C and H-C. Ellipses represent the 95% confidence interval around the group centroid. The P value was calculated by PERMANOVA. Different letters in the boxplot indicate significant differences between the two groups. (C) Significantly different abundant taxa with LDA score (log10) >2.0 and P < 0.05 at the species or genera level, between IgAV-C and H-C groups.

Figure 2

Distinct gut microbiomes were observed in IgAV-M compared to H-M. (A) PCoA and boxplot are shown along the first two principal coordinates of Bray-Curtis distances for IgAV-M and H-M. Ellipses represent the 95% confidence interval around the group centroid. The P value was calculated by PERMANOVA. Different letters in the boxplot indicate significant differences between the two groups. The results showed significant differences in the bacterial community structure between the two groups (B) Significantly different abundant taxa with LDA score (log10) >2.0 and P < 0.05 at the species or genera level, between IgAV-M and H-M groups.

Figure 3

Association between gut microbiome in IgAV children and their mothers. (A) Venn diagram displaying the degree of overlap of bacterial ASVs among IgAV-C, IgAV -M, H-C and H-M. Venn diagrams were constructed to evaluate the number and identity of the shared ASVs among groups. (B) Spearman correlation between abundance of specific taxa in IgAV-C and IgAV-M. (C) Mother-child phylogenies for Lactobacillus and Megamonas. ASVs, only in IgAV-C were represented by triangles and only in IgAV-M by circles. ASVs both in IgAV-M and IgAV-C were labeled with the specific ID in the trees. Lactobacillus at left and Megamonas at right. (A-C), demonstrating that the similarity of the gut microbiome in the IgAV-M + C group.

Figure 4

Distinct gut microbiomes were observed in IgAV children (IgAV-C) compared to healthy controls (H-C) with shotgun metagenomic sequencing. (A) PCoA and boxplot are shown along the first two principal coordinates of Bray-Curtis distances for disease group (include 28 IgAV children) and healthy group (include 27 healthy children). (B) Significantly different abundant taxa with LDA score (log10) >2.0 and P < 0.05 at the species or genera level, between disease and healthy groups.

Figure 5

Differential functional pathways in the gut microbiota and correlation of gut microbiota with clinical indicators. (A) The relative abundance of differential functional pathways in the gut microbiota. The barplot with 95% confidence intervals denote the significantly different microbial pathways between IgAV children and controls. Blue, disease group; yellow, healthy group. (B) Heatmap of Spearman correlation analysis between the gut microbiota and clinical indicators. The results suggested that clinical indicators are associated with differential bacterial abundance. Red and blue indicate positive and negative correlations, respectively. (+/-, P < 0.05).