Project description:Epithelial Ovarian Cancer (EOC) is the leading cause of gynecologic cancer death. Despite many patients achieving remission with first-line therapy, up to 80% of patients will recur and require additional treatment. Retrospective clinical analysis of OC patients indicates antibiotic use during chemotherapy treatment is associated with poor overall survival. We assessed whether antibiotic (ABX) therapy would impact growth of EOC and sensitivity to cisplatin in murine models. Immune competent or compromised mice were given control or ABX containing water (metronidazole, ampicillin, vancomycin, and neomycin) before being intraperitoneally injected with murine EOC cells. Stool was collected to confirm microbiome disruption and tumors were monitored, and cisplatin therapy was administered weekly until endpoint. EOC tumor-bearing mice demonstrate accelerated tumor growth and resistance to cisplatin therapy in ABX treated compared with nonABX treatment. Stool analysis indicated most gut microbial species were disrupted by ABX treatment except for ABX resistant bacteria. To test for role of the gut microbiome, cecal microbiome transplants (CMTs) of microbiota derived from ABX or nonABX treated mice were used to recolonize the microbiome of ABX treated mice. nonABX cecal microbiome was sufficient to ameliorate the chemoresistance and survival of ABX treated mice indicative of a gut derived tumor suppressor. Mechanistically, tumors from ABX treated compared to nonABX treated mice contained a high frequency of cancer stem cells that were augmented by cisplatin. These studies indicate an intact microbiome provides a gut derived tumor suppressor and maintains chemosensitivity that is disrupted by ABX treatment.
Project description:Multiomics of faecal samples collected from individuals in families with multiple cases of type 1 diabetes mellitus (T1DM) over 3 or 4 months. Metagenomic and metatranscriptomic sequencing and metaproteomics were carried out, as well as whole human genome sequencing. Phenotypic data is available.
Project description:We used a DNA microarray chip covering 369 resistance types to investigate the relation of antibiotic resistance gene diversity with humansM-bM-^@M-^Y age. Metagenomic DNA from fecal samples of 123 healthy volunteers of four different age groups, i.e. pre-school Children (CH), School Children (SC), High School Students (HSS) and Adults (AD) were used for hybridization. The results showed that 80 different gene types were recovered from the 123 individuals gut microbiota, among which 25 were present in CH, 37 in SC, 58 in HSS and 72 in AD. Further analysis indicated that antibiotic resistance genes in groups of CH, SC and AD can be independently clustered, and those ones in group HSS are more divergent. The detailed analysis of antibiotic resistance genes in human gut is further described in the paper DNA microarray analysis reveals the antibiotic resistance gene diversity in human gut microbiota is age-related submitted to Sentific Reports The antibiotic resistance gene microarray is custom-designed (Roche NimbleGen), based on a single chip containing 3 internal replicated probe sets of 12 probes per resistance gene, covering the whole 315K 12-plex platform spots.
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.
Project description:We used a DNA microarray chip covering 369 resistance types to investigate the relation of antibiotic resistance gene diversity with humans’ age. Metagenomic DNA from fecal samples of 123 healthy volunteers of four different age groups, i.e. pre-school Children (CH), School Children (SC), High School Students (HSS) and Adults (AD) were used for hybridization. The results showed that 80 different gene types were recovered from the 123 individuals gut microbiota, among which 25 were present in CH, 37 in SC, 58 in HSS and 72 in AD. Further analysis indicated that antibiotic resistance genes in groups of CH, SC and AD can be independently clustered, and those ones in group HSS are more divergent. The detailed analysis of antibiotic resistance genes in human gut is further described in the paper DNA microarray analysis reveals the antibiotic resistance gene diversity in human gut microbiota is age-related submitted to Sentific Reports
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.