The long and winding road to the etiology of idiopathic nephrotic syndrome in children: Focusing on abnormalities in the gut microbiota

2021 ◽  
Author(s):  
Shoji Tsuji ◽  
Kazunari Kaneko
2018 ◽  
Vol 47 (3) ◽  
pp. 164-170 ◽  
Author(s):  
Shoji Tsuji ◽  
Chikushi Suruda ◽  
Masaki Hashiyada ◽  
Takahisa Kimata ◽  
Sohsaku Yamanouchi ◽  
...  

Background: While the etiology of idiopathic nephrotic syndrome (idiopathic nephrotic syndrome [INS]; characterized by repeated relapses and comorbid allergic conditions) remains unknown, recent evidence suggests that dysfunction in regulatory T cells (Tregs) plays an important role in the development of INS as well as allergic diseases. We hypothesized that dysbiosis involving decreased butyric acid-producing gut microbiota leads to defective induction and differentiation of peripherally induced Tregs, resulting in INS relapse. Methods: Study subjects were 12 children with INS, 8 classified as relapsing (R group; median age: 3.0 years) and 4 as non-relapsing (NR group; median age: 4.3 years), and 11 healthy children (HC group; median age: 5.1 years) serving as normal controls. Measurement of microbiota was performed using 16S ribosomal RNA metagenomic analysis, and fecal butyric acid was measured using high performance liquid chromatography. Flow-cytometric analysis of Tregs and CD4-positive (CD4+) cells in peripheral blood was also performed. Results: Metagenomic analysis of gut microbiota using feces showed that the proportion of butyric acid-producing bacteria was significantly lower in R (median 6.36%) than HC (median 18.84%; p = 0.0013), but no different between NR (median 16.71%) and HC (p = 0.29). Fecal organic acid analysis revealed significantly lower butyric acid quantities in R than HC (medians: 0.48 vs. 0.99 mg/g, p = 0.042). Circulating Tregs as a proportion of CD4+ cells were decreased in 75% of R and NR. Conclusion: Pediatric relapsing INS patients show gut microbiota dysbiosis, characterized by a decreased proportion of butyric acid-producing bacteria and lower fecal butyric acid quantities, concomitant with reduced circulatory Tregs.


Author(s):  
Shoji Tsuji ◽  
Shohei Akagawa ◽  
Yuko Akagawa ◽  
Tadashi Yamaguchi ◽  
Jiro Kino ◽  
...  

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Hanchang He ◽  
Minwa Lin ◽  
Lu You ◽  
Tongqing Chen ◽  
Zijie Liang ◽  
...  

Background. Increasing evidences have reported gut microbiota dysbiosis in many diseases, including chronic kidney disease and pediatric idiopathic nephrotic syndrome (INS). There is lack evidence of intestinal microbiota dysbiosis in adults with INS, however. Here, we to address the association between the gut microbiome and INS. Methods. Stool samples of 35 adult INS patients and 35 healthy volunteers were collected. Total bacterial DNA was extracted, and the V4 regions of the bacterial 16S ribosomal RNA gene were sequenced. The fecal microbiome was analyzed using bioinformatics. The correlation analysis between altered taxa and clinical parameters was also included. Results. We found that microbial diversity in the gut was reduced in adult patients with INS. Acidobacteria, Negativicutes, Selenomonadales, Veillonellaceae, Clostridiaceae, Dialister, Rombousia, Ruminiclostridium, Lachnospira, Alloprevotella, Clostridium sensu stricto, Megamonas, and Phascolarctobacterium were significantly reduced, while Pasteurellales, Parabacteroides, Bilophila, Enterococcus, Eubacterium ventriosum, and Lachnoclostridium were markedly increased in patients with INS. In addition, Burkholderiales, Alcaligenaceae, and Barnesiella were negatively correlated with serum creatinine. Blood urea nitrogen levels were positively correlated with Christensenellaceae, Bacteroidales_S24.7, Ruminococcaceae, Ruminococcus, and Lachnospiraceae_NK4A136, but were negatively correlated with Flavonifractor_plautii and Erysipelatoclostridium_ramosum. Enterobacteriales, Enterobacteriaceae, Porphyromonadaceae, Escherichia/Shigella, Parabacteroides, and Escherichia_coli were positively correlated with albumin. Proteinuria was positively correlated with Verrucomicrobia, Coriobacteriia, Thermoleophilia, Ignavibacteria, Coriobacteriales, Nitrosomonadales, Coriobacteriaceae, and Blautia, but was negatively correlated with Betaproteobacteria, Burkholderiales, and Alcaligenaceae. Conclusion. Our findings show compositional alterations of intestinal microbiota in adult patients with INS and correlations between significantly altered taxa and clinical parameters, which points out the direction for the development of new diagnostics and therapeutic approaches targeted intestinal microbiota.


2017 ◽  
Vol 108 ◽  
pp. 35-37 ◽  
Author(s):  
Kazunari Kaneko ◽  
Shoji Tsuji ◽  
Takahisa Kimata

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 365
Author(s):  
Tadashi Yamaguchi ◽  
Shoji Tsuji ◽  
Shohei Akagawa ◽  
Yuko Akagawa ◽  
Jiro Kino ◽  
...  

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.


2007 ◽  
Vol 148 (23) ◽  
pp. 1067-1075
Author(s):  
Krisztina Fischer ◽  
Orsolya Galamb ◽  
Béla Molnár ◽  
Zsolt Tulassay ◽  
András Szabó

A gyermekkori nephrosis 90%-a idiopathiás nephrosis szindróma. Az idetartozó három kórkép, a minimal change betegség, a mesangialis proliferatio és a focalis sclerosis hasonló klinikai képpel jelentkező, eltérő prognózisú és terápiás válaszú betegség. Dolgozatunk célja az idiopathiás nephrosis szindrómába tartozó kórképek kialakulásával, progressziójával összefüggő genetikai ismeretek, génexpressziós változások áttekintése és funkcionális csoportosítása. A génexpressziós változások meghatározásának eszközeként, dolgozatunk röviden összefoglalja a northern blot, a ribonuclease protection assay, az in situ RNS-hibridizáció, a kvantitatív RT-PCR és a microarray módszerek lényegét. Az eddig elvégzett vizsgálatok a DNS-szintézis és repair gének, növekedési faktorok, extracelluláris mátrix, extracelluláris ligandreceptorok, extracelluláris jelátvitel zavarai mellett kiemelik a metabolikus és transzporter gének, illetve az immunszabályozó gének molekuláris eltéréseit, amelyek összefüggésben vannak az idiopathiás nephrosis szindróma eddig megismert molekuláris hátterével. A chiptechnológia fejlődésével és elterjedésével ezek a markerek és a hagyományos vizsgálati módszerek párhuzamos alkalmazása rutindiagnosztikai szempontból is fontossá válhat.


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