Determinants of the microbiome spatial variability in chronic rhinosinusitis.

BACKGROUND: The sinus microbiome in patients with chronic rhinosinusitis (CRS) is considered homogenous across the sinonasal cavity. The middle nasal meatus is the recommended sampling site for 16S rRNA sequencing. However, individuals with unusually high between-site variability between the middle meatus and the sinuses were identified in previous studies. This study aimed to identify which factors determine increased microbial heterogeneity between sampling sites in the sinuses. METHODOLOGY: In this cross-sectional study samples for 16S rRNA sequencing were obtained from the middle meatus, the maxillary and the frontal sinus in 50 patients with CRS. The microbiome diversity between sampling sites was analysed in relation to the size of the sinus ostia and clinical metadata. RESULTS: In approximately 15% of study participants, the differences between sampling sites within one patient were greater than between the patient and other individuals. Contrary to a popular hypothesis, obstruction of the sinus ostium resulted in decreased dissimilarity between the sinus and the middle meatus. The dissimilarity between the sampling sites was patient-specific: greater between-sinus differences were associated with greater meatus-sinus differences, regardless of the drainage pathway patency. Decreased spatial variability was observed in patients with nasal polyps and extensive mucosal changes in the sinuses. CONCLUSIONS: Sampling from the middle meatus is not universally representative of the sinus microbiome. The differences between sites cannot be predicted from the patency of communication pathways between them.

Alterations in intestinal Archaea composition in pediatric patients with Crohn's disease based on next-generation sequencing - a pilot study.

Intestinal dysbiosis can lead to the induction of systemic immune-mediated inflammatory diseases, such as Crohn's disease Although archaea are part of the commensal microbiota, they are still one of the least studied microorganisms. The aim of our study was the standardization of the optimal conditions and primers for sequencing of the gut archaeome using Next Generation Sequencing, and evaluation of the differences between the composition of archaea in patients and healthy volunteers, as well as analysis of the changes that occur in the archaeome of patients depending on disease activity. Newly diagnosed patients were characterized by similar archeal profiles at every taxonomic level as in healthy individuals (the dominance of Methanobacteria at the class level, and Methanobrevibacter at the genus level). In turn, in patients previously diagnosed with Crohn's disease (both in active and remission phase), an increased prevalence of Thermoplasmata, Thermoprotei, Halobacteria (at the class level), and Halococcus, Methanospaera or Picrophilus (at the genus level) were observed. Furthermore, we have found a significant correlation between the patient's parameters and the individual class or species of Archaea. Our study confirms changes in archaeal composition in pediatric patients with Crohn's disease, however, only in long-standing disease. At the beginning of the disease, the archeal profile is similar to that of healthy people. However, in the chronic form of the disease, significant differences in the composition of archaeome begin to appear. It seems that some archaea may be a good indicator of the chronicity and activity of Crohn's disease.

A single dose of dapagliflozin, an SGLT-2 inhibitor, induces higher glycosuria in GCK- and HNF1A-MODY than in type 2 diabetes mellitus.

AIMS: SGLT2 inhibitors are a new class of oral hypoglycemic agents used in type 2 diabetes (T2DM). Their effectiveness in maturity onset diabetes of the young (MODY) is unknown. We aimed to assess the response to a single dose of 10 mg dapagliflozin in patients with Hepatocyte Nuclear Factor 1 Alpha (HNF1A)-MODY, Glucokinase (GCK)-MODY, and type 2 diabetes. METHODS: We examined 14 HNF1A-MODY, 19 GCK-MODY, and 12 type 2 diabetes patients. All studied individuals received a single morning dose of 10 mg of dapagliflozin added to their current therapy of diabetes. To assess the response to dapagliflozin we analyzed change in urinary glucose to creatinine ratio and serum 1,5-Anhydroglucitol (1,5-AG) level. RESULTS: There were only four patients with positive urine glucose before dapagliflozin administration (one with HNF1A-MODY, two with GCK-MODY, and one with T2DM), whereas after SGLT-2 inhibitor use, glycosuria occurred in all studied participants. Considerable changes in mean glucose to creatinine ratio after dapagliflozin administration were observed in all three groups (20.51 ± 12.08, 23.19 ± 8.10, and 9.84 ± 6.68 mmol/mmol for HNF1A-MODY, GCK-MODY, and T2DM, respectively, p < 0.001 for all comparisons). Post-hoc analysis revealed significant differences in mean glucose to creatinine ratio change between type 2 diabetes and each monogenic diabetes in response to dapagliflozin (p = 0.02, p = 0.003 for HNF1-A and GCK MODY, respectively), but not between the two MODY forms (p = 0.7231). Significant change in serum 1,5-AG was noticed only in T2DM and it was -6.57 ± 7.34 mg/ml (p = 0.04). CONCLUSIONS: A single dose of dapagliflozin, an SGLT-2 inhibitor, induces higher glycosuria in GCK- and HNF1A-MODY than in T2DM. Whether flozins are a valid therapeutic option in these forms of MODY requires long-term clinical studies.