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. 2022 Jan 25:11:796410.
doi: 10.3389/fcimb.2021.796410. eCollection 2021.

Integrated Analyses of Gut Microbiome and Host Metabolome in Children With Henoch-Schönlein Purpura

Min Wen  1   2   3 , Xiqiang Dang  1   2 , Shipin Feng  4 , Qingnan He  1   2   3 , Xiaoyan Li  1   2 , Taohua Liu  3 , Xiaojie He  1   2
Affiliations

Integrated Analyses of Gut Microbiome and Host Metabolome in Children With Henoch-Schönlein Purpura

Min Wen et al. Front Cell Infect Microbiol. .

Abstract

Recent studies have shown that intestinal microbes and metabolites are involved in the pathogenesis of many diseases. However, whether and how they are related to Henoch-Schönlein purpura (HSP) has yet to be understood. This work is designed to detect gut microbes, intestinal and serum metabolites in children with HSP, trying to discover the etiology and pathogenesis of HSP. A total of 86 children were recruited in this study, namely, 58 children with HSP (HSP group) and 28 healthy children as control groups (CON group). 16S rDNA amplicon sequencing technology and UPLC-QTOF/MS non-targeted metabolomics analysis were used to detect the intestinal microbes and metabolites, and also multi-reaction monitoring technology for detecting serum arachidonic acid (AA) and its metabolites. Then, correlation analysis was performed to explore the possible interaction between the differential gut microbes and metabolites. As a result, at the microbiota family level, the CON group had an advantage of Coriobacteriaceae while the HSP group had a dominant Bacteroidaceae. Five kinds of bacteria in the HSP group were significantly enriched at the genus level, and seven kinds of bacteria were significantly enriched in the CON group. A total of 59 kinds of gut metabolites significantly differ between the two groups, in which most are lipids and peptides. Spearman correlation analysis showed that Bacteroides, Dialister, and Agathobacter were associated with unsaturated fatty acids, especially AA metabolism. Then, we tested the AA related metabolites in serum and found thromboxane B2, leukotriene B4, prostaglandin D2, 9S-hydroxyoctadecadienoic acid, and 13S-hydroxyoctadecadienoic acid significantly changed. In conclusion, children with HSP had dominant Bacteroidaceae and decreased Coriobacteriaceae in the family level of gut microbes, and also lipids and peptides changed most in the gut metabolites. Our data suggested that the biosynthesis and metabolism of unsaturated fatty acids, especially AA and its metabolites, might participate in the occurrence and development of HSP.

Keywords: 16S rDNA; Arachidonic acid; Henoch-Schönlein purpura; gut microbiota; host metabolome; unsaturated fatty acid.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Intestinal dysbiosis between HSP group and control group. (A) Venn diagram of OTU distribution in HSP group and control group. (B) PCoA analysis between HSP group and control group. (C) Histogram of the distribution of intestinal flora in the HSP group and control group at the phylum level. (D) LDA evolutionary branch diagram by LEfSe analysis. (E) Intestinal flora LEfSe analysis diagram (LDA >2, p < 0.05). (F) KEGG function prediction of intestinal microbes in two groups.
Figure 2
Figure 2
Differences in intestinal flora among the subgroups of HSP and healthy group. (A) Intestinal flora LEfSe analysis diagram between the untreated group (UG) and control group (CON). (B) Intestinal flora LEfSe analysis diagram between the regular treated group (RG) and control group (CON). (C) Intestinal flora LEfSe analysis diagram between the withdrawal group (WG) and control group (CON). (D) Intestinal flora LEfSe analysis diagram between the no renal damage group (NO-RD) and control group (CON). (E) Intestinal flora LEfSe analysis diagram between the renal damage group (RD) and control group (CON). (F) Intestinal flora LEfSe analysis diagram between the no renal damage group (NO-RD) and renal damage group (RD). All LDA >2, p < 0.05.
Figure 3
Figure 3
The KEGG pathway analysis of intestinal metabolites. (A) The differential metabolites related top 20 of the enriched KEGG pathways. (B) Differential intestinal metabolites abundance analysis of KEGG pathways.
Figure 4
Figure 4
Differential gut metabolites among 5 subgroups of HSP and healthy groups in both positive and negative ion modes. (+) shows positive ions, and (−) shows negative ions. UG, the untreated group; CON, the healthy control group; RG, the regular treated group; WG, the withdrawal group; NO-RD, no renal damage group, RD: renal damage group.
Figure 5
Figure 5
Spearman correlation between significantly different intestinal microbes and metabolites. (A) Spearman correlation analysis network diagram of significant difference flora and significant metabolites. Red lines mean positive correlation and blue lines mean negative correlation. The darker the color, the stronger the correlation. (B) Scatter plot of AA with Agathobacter (left) and Bacteroides (right).
Figure 6
Figure 6
Serum AA and its metabolites analysis. * means p < 0.05.
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