Alterations of gut microbiota and metabolome are associated with primary nephrotic syndrome in children.

BACKGROUND

Primary nephrotic syndrome (PNS) is a common glomerular disease in children. Dysbiosis of gut microbiota acts as a cause of Treg abnormalities. However, the intestinal metabolic impact of PNS with children remains poorly understood. This study aims to investigate the dynamic changes of gut microbiota and it's metabolism in children with PNS.

METHODS

Fecal and peripheral blood samples were separately collected from patients with initial diagnosis of PNS (PNS_In group), recurrence of PNS (PNS_Re group), and healthy controls (HCs group). The fecal samples were subjected to the microbiome and metabolome by the multi-omics analysis. Additionally, the peripheral blood samples were collected and associated inflammatory indicators were determined.

RESULTS

We found that in PNS_In group, lipopolysaccharide (LPS), pro-inflammatory interleukin (IL)-6, IL-17A, IL-23p19, and IL-1β were significantly increased compared with those in HCs group. However, these abnormalities were dramatically reversed in PNS_Re group treated with prednisone acetate. Moreover, the crucial Treg/Th17 axis in PNS inflammation was also proved to be discriminated between PNS and HCs. Gut microbial dysbiosis was identified in PNS_In and PNS_Re patients. At the genus level, compared to HCs group, the abundance of Faecalibacterium notably changed in PNS_In and PNS_Re groups, showing negatively correlated with inflammatory factors. Moreover, the fecal metabolome of PNS_In and PNS_Re remarkably altered with the major impacts in the metabolism of phenylalanine, ABC transporters, arginine and proline.

CONCLUSION

The dynamic changes of gut microbiota and associated metabolites are closely correlated with initial period and recurrence of PNS in children via probably regulating inflammatory Th17/Treg axis, which may potentially provide novel targets for the control of the disease.

CLINICAL TRIAL NUMBER: Not applicable.