Clinical Significance of Probiotics for Children with Idiopathic Nephrotic Syndrome

Abstract

We previously reported that a decrease in butyrate-producing bacteria in the gut is a potential cause of regulatory T cell (Treg) abnormalities in children with idiopathic nephrotic syndrome (INS). Therefore, we hypothesized that administration of butyrate-producing bacteria might reduce INS relapse and the need for immunosuppressants in these patients. Twenty patients in remission from INS (median age 5.3 years, 15 boys) were enrolled in the study and assigned to receive either daily oral treatment with a preparation of 3 g Clostridium butyricum or no probiotic treatment. The number of relapses and requirement for immunosuppressive agents were compared between the two groups. In the probiotic treatment group, analyses of the gut microbiota and Treg measurements were also performed. Probiotic-treated patients experienced fewer INS relapses per year compared with non-probiotic-treated patients (p = 0.016). Further, administration of rituximab in the probiotic treatment group was significantly less frequent compared with the non-probiotic-treated group (p = 0.025). In the probiotic treatment group, analyses before and after probiotic treatment revealed the significant increases in the relative abundance of butyrate-producing bacteria (p = 0.017) and blood Treg counts (p = 0.0065). Thus, oral administration of butyrate-producing bacteria during INS remission may reduce the frequency of relapse and the need for immunosuppressive agents.

Keywords: butyrate-producing bacteria; idiopathic nephrotic syndrome; probiotics; regulatory T cells.

Figure 1

Analysis of the diversity of gut microbiota in healthy children and children with idiopathic nephrotic syndrome (INS) before and after Clostridium butyricum MIYAIRI administration. A whisker-plot diagram of Shannon index (a) and number of observed species (b) is shown for each group. Shannon index and the number of observed species were calculated in healthy children as well as children with INS before and after probiotic treatment. There were no significant differences among the three groups in either Shannon index or number of observed species. The central horizontal line in the box represents the median value, while the bottom and top edges of the box represent the first and third quartiles, respectively. Central vertical lines extend from the box to the 90th and 10th percentiles.

Figure 2

Principal coordinate (PC) analysis of the gut microbiota of healthy children and children with idiopathic nephrotic syndrome (INS) before and after probiotic treatment. There were no differences between the three groups. There was also no difference in clusters before and after probiotic treatment.

Figure 3

Changes in the composition of butyrate-producing bacteria in children with idiopathic nephrotic syndrome (INS) before and after Clostridium butyricum MIYAIRI administration. Analysis before and after probiotic treatment revealed a significant increase in the relative abundance of butyrate-producing bacteria at the species level.

Figure 4

Changes in Treg frequencies after administration of C. butyricum MIYAIRI as a probiotic to patients with INS. Treg frequencies were measured at three time points: at the onset of INS, immediately after the end of prednisolone administration following induction of initial remission, and 1.5 to 2 months after starting probiotic administration following prednisolone cessation. (a) Probiotic-treated group: There was a significant increase in the number of Tregs after comparing with before probiotic treatment. (b) Non-probiotic treatment group: in the seven patients in the non-probiotic treatment group, there was no statistically significant increase in the number of Tregs at onset, immediately after the end of prednisolone treatment, and approximately 2 months after the end of prednisolone treatment.