Recent studies have established that the etiology of HSP includes both genetic and environmental components (18) (19). However, it is only the beginning to elucidate the environmental factors that may be involved in the development of HSP and the molecular mechanisms through which these factors function. The high incidence of HSP and the severe symptoms of purpura make it important to understand the microbiome of people with high incidence of purpura. In our previous study, we discovered the potential correlation of gut microbiota dysbiosis with HSP in children (8). Furthermore, multiple studies have indicated that in addition to genetic influences, the maternal gut microbiota may play an essential role in the occurrence of diseases in offspring during gestation and exhibits continuous correlations and long-term pathological consequences during development (9). However, it remains unclear whether the maternal gut bacterial communities have associations with that of the HSP children, and whether the HSP children harbor unique gut microbial taxon that may be the key players in pathogenesis. To the best of our knowledge, no previous studies have investigated the gut microbiome of HSP children and their mothers in parallel and evaluated their correlations.
Our study is pilot to examine the correlations between the microbiome profiles of HSP children and their mothers. We found that the gut microbiota of HSP children and their mother displayed a remarkable dysbiosis, including decreased bacterial diversity and richness (Fig. 1), as well as a different microbiota structure when compared with that of healthy children and their mother. Additionally, while there were close correlations between the microbiome profiles of mother-child pairs, the HSP children exhibited unique bacterial biomarkers. Finally, the identified bacterial biomarkers exhibited remarkable discriminatory power for differentiating HSP children from control children and their mothers. These biomarkers may serve as critical pathogenetic bacteria that deserve further investigations.
Consistent with our previous clinical studies on the gut microbiome of HSP children, a comparison of the gut bacterial community structures between HSP children and healthy controls in our study revealed significantly shifted microbiome profiles in the feces of HSP children and identified a set of bacterial biomarkers that varied significantly between the two groups, such as Enterococcus, which has been reported to be associated with immune diseases such as eczema (20). Similarly, Dialister and Roseburia were markedly decreased in the HSP-C. Roseburia also had been found decrease in patients with ulcerative colitis (21), which plays a major role in maintenance of colonic mucosal health and anti-inflammation by producing butyrat (22) (23, 24).
Surprisingly, HSP-M showed significantly different gut microbiome with H-M, although both of them are basically “healthy” females. Interestingly, whether it is an HSP child or a healthy child, his/her gut microbiome composition is more similar to that of his/her mother. Each mother-child pair group seems to possess distinct core microbiome. These results indicate that gut microbiome can be vertically transmitted from the mother to the gut of offspring, which could partially explain the similarities in the gut microbiome profiles of the mother-child pairs (25). Further studies are required to identify the specific causes of these variations and associations.
We found HSP-C and HSP-M share common biomarkers, such as Prevotella and Megamonas, whereas Lachnospira, Haemophilus, and Akkermansia were decreased in both HSP-C and HSP-M group. Haemophilus also has been found decreased in the gut of rheumatoid arthritis patients (26) and food allergy of children (27). Although HSP-C and HSP-M share common biomarkers, the distinct gut bacterial biomarkers of HSP children also included four species showing increased abundance compare with their mother, namely, Enterococcus, Fusobacterium, Veillonella and Streptococcus. Notably, Streptococcus were found to be increased in HSP children but decreased in HSP-M. Enterococcus is a major commensal bacteria in the human digestive tract and also the main opportunistic pathogen in the human gut reports, which was reported to be related to acquired immunodeficiency syndrome (28), Henoch-Schönlein purpura (8), and Crohn's disease (29). A recent study suggested that Veillonella parvula strongly induces IL-6, a proinflammatory cytokine involved in the development of immune system diseases (29). Veillonella also has been associated with the development of a healthy immune system in infants (30). And gut Streptococcus has been reported can affect persistence and severity of atopic dermatitis during infancy (31).
A dysbiotic gut microbiota has been associated with allergic diseases (32). Based on the discovered biomarkers, HSP children and the mothers of HSP children could be separated from healthy children and their mothers with high sensitivity and specificity. The discriminatory power of these candidate biomarkers paves the way for establishing fecal microbiome tests for clinical diagnostic and prognostic screening for HSP. However, our study had some limitations. First, the cross-sectional nature of the study did not enable us to elucidate the mechanisms and longitudinal aspects of the correlations. Additional large cohort studies are needed to establish the time sequence and evaluate changes in the gut microbiome of mothers and children. Furthermore, the small sample size did not allow subgroup analysis to assess whether the correlations were consistent across different patients with HSP, as defined by factors such as severity and comorbidity. However, this does not detract from the potential value of these biomarkers for clinical validation and applications, which is currently being evaluated in a nested, case-controlled study using a population-based cohort.