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Updated: May 28, 2025

Microbiota Analysis Using Two-step PCR and Next-generation 16S rRNA Gene Sequencing
Published on: October 15, 2019
Gut microbiota, inflammatory cytokines, and Kawasaki disease: a Mendelian randomization study and mediation analysis
Ji-Gan Wang1, Hui-Hong Dou2, Qiong-You Liang2
1Department of Pediatrics, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Guangxi Clinical Research Center for Pediatric Diseases, Nanning, China. wangjigan@163.com.
Objective:
This study investigates the causal relationship between gut microbiota, inflammatory cytokines, and Kawasaki disease (KD), and whether cytokines mediate the effect of gut microbiota on KD.
Methods:
A Mendelian randomization analysis using the inverse-variance weighted method assessed the causal effects of gut microbiota and inflammatory cytokines on KD and explored potential mediation.
Results:
The study found causal links between 20 types of gut microbiota and KD. Ten types increased KD risk, notably Francisellales (OR = 27.82, P = 0.0309). Ten types provided protection, with Fusobacteriaceae showing the strongest effect (OR = 0.0424, P = 0.002). Five inflammatory cytokines were significantly associated with KD; adenosine deaminase was most protective (OR = 0.7447, P = 0.0037), while Fractalkine indicated higher risk (OR = 2.0448, P = 0.0315). Mediation analysis revealed that the Interleukin-10 receptor subunit beta mediates the effect of Bifidobacterium adolescentis on KD, with a mediation effect of -0.0237 (4.75% ratio). Interleukin-20 mediates the effect of Faecalicatena lactaris on KD, with a mediation effect of -0.1168 (15.30% ratio).
Conclusion:
The findings indicate a causal relationship among gut microbiota, inflammatory cytokines, and KD, suggesting that the gut microbiome influences KD through specific cytokines.
Impact:
The study confirmed a causal relationship between 20 types of gut microbiota and Kawasaki disease, finding that 10 types increase the risk of Kawasaki disease, particularly Francisellales. Five inflammatory cytokines were significantly associated with Kawasaki disease, with adenosine deaminase showing a protective effect, while Fractalkine increased the risk. Mediation analysis indicated that specific inflammatory cytokines (such as Interleukin-10 receptor subunit beta and Interleukin-20) play a significant mediating role between gut microbiota and Kawasaki disease.
Insights
This study reveals that gut bacteria influence Kawasaki disease (KD) risk, with some microbes increasing or decreasing susceptibility. Specific inflammatory cytokines mediate these effects, highlighting a gut microbiome connection to KD.
Area of Science:
- Microbiome research
- Immunology
- Pediatric disease
Background:
- Kawasaki disease (KD) is an acute febrile vasculitis affecting young children.
- The etiology of KD remains unclear, but the gut microbiome and inflammatory responses are implicated.
- Understanding the interplay between gut microbiota and inflammatory cytokines in KD is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the causal relationship between gut microbiota composition and Kawasaki disease (KD).
- To examine the association between inflammatory cytokines and KD.
- To determine if inflammatory cytokines mediate the influence of gut microbiota on KD development.
Main Methods:
- Mendelian randomization analysis was employed to assess causal effects.
- Inverse-variance weighted method was utilized for statistical analysis.
- Mediation analysis explored the role of cytokines in the gut microbiota-KD pathway.
Main Results:
- Causal links were established between 20 gut microbial types and KD.
- Francisellales significantly increased KD risk (OR=27.82), while Fusobacteriaceae showed a protective effect (OR=0.0424).
- Adenosine deaminase exhibited a protective association with KD (OR=0.7447), whereas Fractalkine was linked to increased risk (OR=2.0448).
- Interleukin-10 receptor subunit beta and Interleukin-20 were identified as mediators in the gut microbiota-KD relationship.
Conclusions:
- Gut microbiota composition causally influences Kawasaki disease risk.
- Specific inflammatory cytokines mediate the impact of gut microbes on KD pathogenesis.
- Targeting the gut microbiome and associated inflammatory pathways may offer novel therapeutic strategies for KD.
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