Prior antibiotic administration disrupts outcomes of PD-1 blockade in advanced gastric cancer by altering gut microbiome and systemic immune response
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE229379 | GEO | 2023/07/01
REPOSITORIES: GEO
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2022-10-10 | GSE214348 | GEO
Project description:OBJECTIVE:Antibiotics have been a mainstay of chronic rhinosinusitis therapy; however, data suggest that antibiotics may also result in several adverse unintended consequences. We aimed to evaluate if greater antibiotic use prior to sinus surgery was associated with differences in surgical outcomes. METHODS:Adult CRS patients enrolled in a prospective, multi-institutional, observational cohort study were asked to recall systemic antibiotic use in the 90 days prior to endoscopic sinus surgery (ESS). Antibiotic use was examined in relation to demographics, disease characteristics, and outcomes. RESULTS:Data were collected for 271 study participants followed for a mean of 14.9 [±?5.1] months across four institutions, with a mean preoperative antibiotic use of 27.8 [±?22.7] days out of the 90 preceding ESS. After ESS, significant improvement (P?<?0.001) was reported for patient-reported outcome measures and endoscopy scores for the overall cohort. No bivariate correlation between preoperative antibiotic use and degree of benefit in objective clinical measures (endoscopy, Brief Smell Identification Test) was seen. Increased preoperative antibiotic use was associated with less improvement in 22-item SinoNasal Outcome Test (SNOT-22) and its rhinologic subdomain after ESS. Prevalence of achieving a minimal clinically important difference in overall SNOT-22 symptom scores was lower in those using more preoperative antibiotics, although statistical significance was not reached when adjusting for independent covariates in multivariate modeling. CONCLUSION:Higher amounts of previous antibiotic use do not appear to be associated with better ESS outcomes. Specific recommendations for antibiotic use as part of CRS-appropriate medical therapy prior to ESS require further study, particularly given concerns for antibiotic overuse and implications for improving outcomes in the modern healthcare era. LEVEL OF EVIDENCE:2C Laryngoscope, 129:558-566, 2019.
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Project description:The atypical antipsychotic olanzapine is often associated with serious metabolic side effects including weight gain and increased visceral fat. These adverse events are a considerable clinical problem and the mechanisms underlying them are multifactorial and poorly understood. Growing evidence suggests that the gut microbiota has a key role in energy regulation and disease states such as obesity. Moreover, we recently showed that chronic olanzapine altered the composition of the gut microbiome in the rat. It is thus possible that treatments that alter gut microbiota composition could ameliorate olanzapine-induced weight gain and associated metabolic syndrome. To this end, we investigated the impact of antibiotic-induced alteration of the gut microbiota on the metabolic effects associated with chronic olanzapine treatment in female rats. Animals received vehicle or olanzapine (2 mg kg(-1) per day) for 21 days, intraperitoneal injection, two times daily. Animals were also coadministered vehicle or an antibiotic cocktail consisting of neomycin (250 mg kg(-1) per day), metronidazole (50 mg kg(-1) per day) and polymyxin B (9 mg kg(-1) per day) by oral gavage, daily, beginning 5 days before olanzapine treatment. The antibiotic cocktail drastically altered the microbiota of olanzapine-treated rats, and olanzapine alone was also associated with an altered microbiota. Coadministration of the antibiotic cocktail in olanzapine-treated rats attenuated: body weight gain, uterine fat deposition, macrophage infiltration of adipose tissue, plasma free fatty acid levels, all of which were increased by olanzapine alone. These results suggest that the gut microbiome has a role in the cycle of metabolic dysfunction associated with olanzapine, and could represent a novel therapeutic target for preventing antipsychotic-induced metabolic disease.
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Project description:Early gastric cancers (EGC) precede advanced gastric cancers (AGC) with a favorable clinical outcome compared to advanced gastric cancers (AGC). To understand the progression mechanisms of EGC to AGC, it is required to disclose the EGC and AGC genomes in terms of the the mutational and evolutionary perspectives. In this study, we performed whole-exome sequencing and copy number profiling of nine microsatellite (MS)-unstable (MSI-H) (5 EGC and 4 AGC) and eight MS-stable (MSS) gastric cancers (4 EGC and 4 AGC). Unexpectedly, we observed no substantial differences in the number, sequence composition and functional consequences (potential driver mutations and affected pathways) of the mutations and CNAs between EGC and AGC genomes in both MSI-H and MSS cases.
2014-06-30 | GSE57176 | GEO
Project description:BackgroundMass drug administration (MDA) with azithromycin is the primary strategy for global trachoma control efforts. Numerous studies have reported secondary effects of MDA with azithromycin, including reductions in childhood mortality, diarrhoeal disease and malaria. Most recently, the MORDOR clinical trial demonstrated that MDA led to an overall reduction in all-cause childhood mortality in targeted communities. There is however concern about the potential of increased antimicrobial resistance in treated communities. This study evaluated the impact of azithromycin MDA on the prevalence of gastrointestinal carriage of macrolide-resistant bacteria in communities within the MORDOR Malawi study, additionally profiling changes in the gut microbiome after treatment. For faecal metagenomics, 60 children were sampled prior to treatment and 122 children after four rounds of MDA, half receiving azithromycin and half placebo.ResultsThe proportion of bacteria carrying macrolide resistance increased after azithromycin treatment. Diversity and global community structure of the gut was minimally impacted by treatment, however abundance of several species was altered by treatment. Notably, the putative human enteropathogen Escherichia albertii was more abundant after treatment.ConclusionsMDA with azithromycin increased carriage of macrolide-resistant bacteria, but had limited impact on clinically relevant bacteria. However, increased abundance of enteropathogenic Escherichia species after treatment requires further, higher resolution investigation. Future studies should focus on the number of treatments and administration schedule to ensure clinical benefits continue to outweigh costs in antimicrobial resistance carriage. Trial registration ClinicalTrial.gov, NCT02047981. Registered January 29th 2014, https://clinicaltrials.gov/ct2/show/NCT02047981.
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