Diabetes mellitus is a chronic disease affecting glucose metabolism. The pathophysiological reactions underpinning the disease can lead to the development of late diabetes complications. The gut microbiota plays important roles in weight regulation and the maintenance of a healthy digestive system. Obesity, diabetes mellitus, diabetic retinopathy, diabetic nephropathy and diabetic neuropathy are all associated with a microbial imbalance in the gut. Modern technical equipment and advanced diagnostic procedures, including xmolecular methods, are commonly used to detect both quantitative and qualitative changes in the gut microbiota. This review summarises collective knowledge on the role of the gut microbiota in both types of diabetes mellitus and their late complications, with a particular focus on diabetic foot syndrome.
- MeSH
- diabetes mellitus * MeSH
- diabetická noha * MeSH
- diabetická retinopatie * MeSH
- diabetické nefropatie * etiologie MeSH
- lidé MeSH
- obezita MeSH
- střevní mikroflóra * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
AIMS/HYPOTHESIS: The aim of this substudy (Eudra CT No:2019-001997-27)was to assess ATB availability in patients with infected diabetic foot ulcers(IDFUs)in the context of microcirculation and macrocirculation status. METHODS: For this substudy, we enrolled 23 patients with IDFU. Patients were treated with boluses of amoxicillin/clavulanic acid(AMC)(12patients) or ceftazidime(CTZ)(11patients). After induction of a steady ATB state, microdialysis was performed near the IDFU. Tissue fluid samples from the foot and blood samples from peripheral blood were taken within 6 hours. ATB potential efficacy was assessed by evaluating the maximum serum and tissue ATB concentrations(Cmax and Cmax-tissue)and the percentage of time the unbound drug tissue concentration exceeds the minimum inhibitory concentration (MIC)(≥100% tissue and ≥50%/60% tissue fT>MIC). Vascular status was assessed by triplex ultrasound, ankle-brachial and toe-brachial index tests, occlusive plethysmography comprising two arterial flow phases, and transcutaneous oxygen pressure(TcPO2). RESULTS: Following bolus administration, the Cmax of AMC was 91.8 ± 52.5 μgmL-1 and the Cmax-tissue of AMC was 7.25 ± 4.5 μgmL-1(P<0.001). The Cmax for CTZ was 186.8 ± 44.1 μgmL-1 and the Cmax-tissue of CTZ was 18.6 ± 7.4 μgmL-1(P<0.0001). Additionally, 67% of patients treated with AMC and 55% of those treated with CTZ achieved tissue fT>MIC levels exceeding 50% and 60%, respectively. We observed positive correlations between both Cmax-tissue and AUCtissue and arterial flow. Specifically, the correlation coefficient for the first phase was r=0.42; (P=0.045), and for the second phase, it was r=0.55(P=0.01)and r=0.5(P=0.021). CONCLUSIONS: Bactericidal activity proved satisfactory in only half to two-thirds of patients with IDFUs, an outcome that appears to correlate primarily with arterial flow.
- MeSH
- antibakteriální látky * farmakokinetika aplikace a dávkování terapeutické užití MeSH
- diabetická noha * farmakoterapie metabolismus MeSH
- intravenózní podání MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikrocirkulace * účinky léků MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Cutaneous leishmaniasis, a parasitic disease caused by Leishmania major, is a widely frequent form in humans. To explore the importance of the host gut microbiota and to investigate its changes during L. major infection, two different groups of mouse models were assessed. The microbiome of two parts of the host gut-ileum and colon-from infected and non-infected mice were characterised by sequencing of 16S rDNA using an Ion Torrent PGM platform. Microbiome analysis was performed to reveal changes related to the susceptibility and the genetics of mice strains in two different gut compartments and to compare the results between infected and non-infected mice. The results showed that Leishmania infection affects mainly the ileum microbiota, whereas the colon bacterial community was more stable. Different biomarkers were determined in the gut microbiota of infected resistant mice and infected susceptible mice using LEfSe analysis. Lactobacillaceae was associated with resistance in the colon microbiota of all resistant mice strains infected with L. major. Genes related to xenobiotic biodegradation and metabolism and amino acid metabolism were primarily enriched in the small intestine microbiome of resistant strains, while genes associated with carbohydrate metabolism and glycan biosynthesis and metabolism were most abundant in the gut microbiome of the infected susceptible mice. These results should improve our understanding of host-parasite interaction and provide important insights into the effect of leishmaniasis on the gut microbiota. Also, this study highlights the role of host genetic variation in shaping the diversity and composition of the gut microbiome. KEY POINTS: • Leishmaniasis may affect mainly the ileum microbiota while colon microbiota was more stable. • Biomarkers related with resistance or susceptibility were determined in the gut microbiota of mice. • Several pathways were predicted to be upregulated in the gut microbiota of resistant or susceptible mice.
- MeSH
- biologické markery MeSH
- Leishmania major * MeSH
- leishmanióza kožní * MeSH
- lidé MeSH
- myši MeSH
- náchylnost k nemoci mikrobiologie MeSH
- střevní mikroflóra * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The present study investigated whether neonatal exposure to the proinflammatory endotoxin lipopolysaccharide (LPS) followed by an antibiotic (ATB)-induced dysbiosis in early adulthood could induce neurodevelopmental disorders-like behavioral changes in adult male rats. Combining these two stressors resulted in decreased weight gain, but no significant behavioral abnormalities were observed. LPS treatment resulted in adult rats' hypoactivity and induced anxiety-like behavior in the social recognition paradigm, but these behavioral changes were not exacerbated by ATB-induced gut dysbiosis. ATB treatment seriously disrupted the gut bacterial community, but dysbiosis did not affect locomotor activity, social recognition, and acoustic reactivity in adult rats. Fecal bacterial community analyses showed no differences between the LPS challenge exposed/unexposed rats, while the effect of ATB administration was decisive regardless of prior LPS exposure. ATB treatment resulted in significantly decreased bacterial diversity, suppression of Clostridiales and Bacteroidales, and increases in Lactobacillales, Enterobacteriales, and Burkholderiales. The persistent effect of LPS on some aspects of behavior suggests a long-term effect of early toxin exposure that was not observed in ATB-treated animals. However, an anti-inflammatory protective effect of ATB cannot be assumed because of the increased abundance of pro-inflammatory, potentially pathogenic bacteria (Proteus, Suttrella) and the elimination of the bacterial families Ruminococcaceae and Lachnospiraceae, which are generally considered beneficial for gut health.
- Publikační typ
- časopisecké články MeSH
