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INTRODUCTION: Chronic kidney disease (CKD), a progressive loss of renal function, can lead to serious complications if underdiagnosed. Many studies suggest that the oral microbiota plays important role in the health of the host; however, little is known about the association between the oral microbiota and CKD pathogenesis. METHODS: In this study, we surveyed the oral microbiota in saliva, the left and right molars, and the anterior mandibular lingual area from 77 participants (18 with and 59 without CKD), and tested their association with CKD to identify microbial features that may be predictive of CKD status. RESULTS: The overall oral microbiota composition significantly differed by oral locations and was associated with CKD status in saliva and anterior mandibular lingual samples. In CKD patients, we observed a significant enrichment of Neisseria and depletion of Veillonella in both sample types and a lower prevalence of Streptococcus in saliva after adjustment for other comorbidities. Furthermore, we detected a negative association of Neisseria and Streptococcus genera with the kidney function as measured by estimated glomerular filtration rate. Neisseria abundance also correlated with plasma interleukin-18 levels. CONCLUSION: We demonstrate the association of the oral microbiome with CKD and inflammatory kidney biomarkers, highlighting a potential role of the commensal bacteria in CKD pathogenesis. A better understanding of the interplay between the oral microbiota and CKD may help in the development of new strategies to identify at-risk individuals or to serve as a novel target for therapeutic intervention.
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BACKGROUND: Craniosynostosis is a condition that includes the premature fusion of one or multiple cranial sutures. Among various craniosynostosis forms, sagittal nonsyndromic craniosynostosis is the most prevalent. Although different gene mutations have been identified in some craniosynostosis syndromes, the cause of sagittal nonsyndromic craniosynostosis remains largely unknown. METHODS: To screen for candidate genes for sagittal nonsyndromic craniosynostosis, the authors sequenced DNA of 93 sagittal nonsyndromic craniosynostosis patients from a population-based study conducted in Iowa and New York states. FGFR1-3 mutational hotspots and the entire TWIST1, RAB23, and BMP2 coding regions were screened because of their known roles in human nonsyndromic or syndromic sagittal craniosynostosis, expression patterns, and/or animal model studies. RESULTS: The authors identified two rare variants in their cohort. A FGFR1 insertion c.730_731insG, which led to a premature stop codon, was predicted to abolish the entire immunoglobulin-like III domain, including the ligand-binding region. A c.439C>G variant was observed in TWIST1 at its highly conserved loop domain in another patient. The patient's mother harbored the same variant and was reported with jaw abnormalities. These two variants were not detected in 116 alleles from unaffected controls or seen in the several databases; however, TWIST1 variant was found in a low frequency of 0.000831 percent in Exome Aggregation Consortium database. CONCLUSIONS: The low mutation detection rate indicates that these genes account for only a small proportion of sagittal nonsyndromic craniosynostosis patients. The authors' results add to the perception that sagittal nonsyndromic craniosynostosis is a complex developmental defect with considerable genetic heterogeneity. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.