Dataset Information

Our Evolving Understanding of Kawasaki Disease Pathogenesis: Role of the Gut Microbiota.

ABSTRACT: Kawasaki disease (KD) was first described by Dr. Tomisaku Kawasaki in 1967. The etiology of KD has been studied comprehensively but remains largely unknown. The disease seems to result from the interplay of genetic and environmental susceptibility factors with infectious triggers, followed by a subsequent abnormal immune response characterized by increased levels of inflammatory cytokines and chemokines during the acute phase. Evidence has mounted to suggest that an imbalance between T helper 17 cells (Th17s) and regulatory T cells (Tregs) is associated with aberrant immune responses in KD. Recent advances in culture-independent techniques for detection and identification of intestinal commensal bacteria enabled the discovery that Th17 and Treg differentiation are regulated by short chain fatty acids (SCFAs), in particular butyrate, produced by the gut microbiota. This finding provided a mechanistic link between dysbiosis, defined as changes in the composition of the gut microbiota, and various inflammatory diseases. On this basis, we propose that dysbiosis, with reduced production of SCFAs leading to imbalances of Th17s/Tregs, could be involved in the etiology of KD. A pilot study supported this hypothesis, as only fecal concentrations of butyrate were significantly reduced in KD patients among SCFAs. This evolving perspective prompted us to undertake metagenomic analyses of bacterial DNA from the feces of KD patients who were antibiotic-naïve at diagnosis. Simultaneous measurements of Th17s/Tregs in peripheral blood and SCFA concentrations in feces would provide valuable information regarding the association between dysbiosis and dysregulated immune responses in KD.

SUBMITTER: Kaneko K

PROVIDER: S-EPMC7393004 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Our Evolving Understanding of Kawasaki Disease Pathogenesis: Role of the Gut Microbiota.

Kaneko Kazunari K Akagawa Shohei S Akagawa Yuko Y Kimata Takahisa T Tsuji Shoji S

Frontiers in immunology 20200724

Kawasaki disease (KD) was first described by Dr. Tomisaku Kawasaki in 1967. The etiology of KD has been studied comprehensively but remains largely unknown. The disease seems to result from the interplay of genetic and environmental susceptibility factors with infectious triggers, followed by a subsequent abnormal immune response characterized by increased levels of inflammatory cytokines and chemokines during the acute phase. Evidence has mounted to suggest that an imbalance between T helper 17 ...[more]

PMID: 32793240

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Project description:BackgroundKawasaki disease (KD) is an acute febrile illness of early childhood. The exact etiology of the disease remains unknown. At present, research on KD is mostly limited to susceptibility genes, infections, and immunity. However, research on the correlation between gut microbiota and KD is rare.MethodsChildren with a diagnosis of acute KD and children undergoing physical examination during the same period were included. At the time of admission, the subjects' peripheral venous blood and feces were collected. Faecal samples were analyzed for bacterial taxonomic content via high-throughput sequencing. The abundance, diversity, composition, and characteristic differences of the gut microbiota in KD and healthy children were compared by alpha diversity, beta diversity, linear discriminant analysis and LDA effect size analysis. Blood samples were used for routine blood examination, biochemical analysis, and immunoglobulin quantitative detection.ResultsCompared with the control group, the community richness and structure of gut microbiota in the KD group was significantly reduced (Chao1 richness estimator, mean 215.85 in KD vs. mean 725.76 in control, p < 0.01; Shannon diversity index, mean 3.32 in KD vs. mean 5.69 in control, p < 0.05). LEfSe analysis identified two strains of bacteria significantly associated with KD: Bacteroidetes and Dorea. Bacteroidetes were enriched in healthy children (mean 0.16 in KD vs. mean 0.34 in control, p < 0.05). Dorea was also enriched in healthy children but rarely existed in children with KD (mean 0.002 in KD vs. mean 0.016 in control, p < 0.05). Compared with the control, IgA and IgG in the KD group decreased (IgA, median 0.68 g/L in KD vs. median 1.06 g/L in control, p < 0.001; IgG, median 6.67 g/L in KD vs. median 9.71 g/L in control, p < 0.001), and IgE and IgM levels were not significantly changed.ConclusionsDysbiosis of gut microbiota occurs in children with acute KD and may be related to the etiology or pathogenesis of KD. It is worth noting that for the first time, we found that Dorea, a hydrogen-producing bacterium, was significantly reduced in children with acute KD. Overall, our results provide a theoretical basis for the prevention or diagnosis of KD based on intestinal microecology.

Project description:Type 1 Diabetes (T1D) is regarded as an autoimmune disease characterized by insulin deficiency resulting from destruction of pancreatic β-cells. The incidence rates of T1D have increased worldwide. Over the past decades, progress has been made in understanding the complexity of the immune response and its role in T1D pathogenesis, however, the trigger of T1D autoimmunity remains unclear. The increasing incidence rates, immigrant studies, and twin studies suggest that environmental factors play an important role and the trigger cannot simply be explained by genetic predisposition. Several research initiatives have identified environmental factors that potentially contribute to the onset of T1D autoimmunity and the progression of disease in children/young adults. More recently, the interplay between gut microbiota and the immune system has been implicated as an important factor in T1D pathogenesis. Although results often vary between studies, broad compositional and diversity patterns have emerged from both longitudinal and cross-sectional human studies. T1D patients have a less diverse gut microbiota, an increased prevalence of Bacteriodetes taxa and an aberrant metabolomic profile compared to healthy controls. In this comprehensive review, we present the data obtained from both animal and human studies focusing on the large longitudinal human studies. These studies are particularly valuable in elucidating the environmental factors that lead to aberrant gut microbiota composition and potentially contribute to T1D. We also discuss how environmental factors, such as birth mode, diet, and antibiotic use modulate gut microbiota and how this potentially contributes to T1D. In the final section, we focus on existing recent literature on microbiota-produced metabolites, proteins, and gut virome function as potential protectants or triggers of T1D onset. Overall, current results indicate that higher levels of diversity along with the presence of beneficial microbes and the resulting microbial-produced metabolites can act as protectors against T1D onset. However, the specifics of the interplay between host and microbes are yet to be discovered.

Dataset Information

Our Evolving Understanding of Kawasaki Disease Pathogenesis: Role of the Gut Microbiota.

Publications

Our Evolving Understanding of Kawasaki Disease Pathogenesis: Role of the Gut Microbiota.

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