Project description:The link between human gut microbiota (a complex group of microorganisms including not only bacteria but also fungi, viruses, etc.,) and the physiological state is nowadays unquestionable. Metaproteomic has emerged as a useful technique to characterize this microbial community, not just taxonomically, but also focusing on specific biological processes carried out by gut microbiota that may have an effect in the host health or pathological state. Cystic fibrosis is a genetic disease in which the microbiota of the respiratory tract determines the patient's survival and differences in composition of gut microbiota of cystic fibrosis patients respect to healthy infants have been reported. In order to characterize this host-microbiota inter-relation, we carried out the metaproteomic study of 30 stool samples from infants with cystic fibrosis.
Project description:The complex milieu of inflammatory mediators associated with many diseases is often too dilute to directly measure in the periphery, necessitating development of more sensitive measurements suitable for mechanistic studies, earlier diagnosis, guiding selection of therapy, and monitoring interventions. Previously, we determined that plasma of recent-onset (RO) Type 1 diabetes (T1D) patients induce a proinflammatory transcriptional signature in fresh peripheral blood mononuclear cells (PBMC) relative to that of unrelated healthy controls (HC). Here, using an optimized cryopreserved PBMC-based protocol, we compared the signature found between unrelated healthy controls and non-diabetic cystic fibrosis patients possessing Pseudomonas aeruginosa pulmonary tract infection. UPN727 cells were stimulated with autologous plasma (n=5), unrelated healthy control plasma (n=24), or plasma from patients with cystic fibrosis possessing Psuedomonas aeruginosa pulmonary tract infection (n=20). Gene expression analysis was perfromed in order to evaluate the transcriptional signature associated with cystic fibrosis.
Project description:Mammalian species have co-evolved with intestinal microbial communities that can shape development and adapt to environmental changes, including antibiotic perturbation or nutrient flux. In humans, especially children, microbiota disruption is common, yet the dynamic microbiome recovery from early-life antibiotics is still uncharacterized. Using a mouse model mimicking pediatric antibiotic use, we found that therapeutic-dose pulsed antibiotic treatment (PAT) with a beta-lactam or macrolide altered both host and microbiota development. Early-life PAT accelerated total mass and bone growth, and resulted in progressive changes in gut microbiome diversity, population structure, and metagenomic content, with microbiome effects dependent on the number of courses and class of antibiotic. While control microbiota rapidly adapted to a change in diet, PAT slowed the ecological progression, with delays lasting several months in response to the macrolide. This study identifies key markers of disturbance and recovery, which may help provide therapeutic targets for microbiota restoration following antibiotic treatment. C57BL/6J mice received three antibiotic courses: at days 10-15, 28-31, and 37-40 of life, amoxicillin or tylosin.Livers were collected at age 22 weeks, RNA was extracted, and transcriptional differences were measured by microarray analysis.