Biology subjects

Pottenger, S.

Publications and source records attributed to Pottenger, S..

2 recordsLinked to original sources

bioRxiv2024

Sputum Proteomics reveals unique signatures linked to key outcomes in cystic fibrosis trials.

RationaleLung function (FEV1) and quality of life (QoL) are key outcomes in most interventional clinical trials conducted in people living with cystic fibrosis. However, no robust pre-clinical surrogates for FEV1 and QoL exist. The precise physiological mechanisms leading to treatment-related improvements in these outcomes are incompletely understood. In this post-hoc analysis we explored the relationship between changes in the sputum proteome and these outcomes with the aim of identifying translational biomarkers. MethodsPaired sputum samples collected during the AZTEC-CF study (NCT02894684) pre and post 14 days of antibiotic treatment for an acute pulmonary exacerbation were included. Samples were analysed using in vitro Mesoscale Discovery (MSD) assays and by nano LC-MS/MS. Peptide identification and quantification was performed and the log-fold change for individual proteins and relationships between protein change and changes in FEV1 and QoL were evaluated. ResultsDistinct patterns were found between proteins that correlated with FEV1 and those that correlated with QoL improvements. FEV1 improvement was characterised by increases in bacterially-derived proteins accompanied by decreases in proteins relating to neutrophil degranulation. Conversely, changes in QoL were associated with increases in antiprotease and antioxidant proteins. MSD analysis revealed changes in some neutrophil-associated markers significantly correlated with FEV1 improvements, but no markers significantly correlated with QoL improvements. ConclusionsThese results suggest changes in two key CF clinical trial outcomes (FEV1 and QoL) may be underpinned by different physiological mechanisms. Understanding these divergent mechanisms is vital to fortify optimal clinical trial design in CF and panels of biomarkers may be needed to improve translational confidence.

immunology↗

bioRxiv2022

Timing and Delivery route effects of Cecal Microbiome transplants on Salmonella Typhimurium infections in Chickens

BackgroundExposure to microbes early in life has long-lasting effects on microbial community structure and function of the microbiome. However, in commercial poultry settings chicks are reared as a single-age cohort with no exposure to adult birds which can have profound effects on microbiota development and subsequent pathogen challenge. Microbiota manipulation is a proven and promising strategy to help reduce pathogen load and transmission within broiler flocks. ResultsManipulation of the microbiota between 4 and 72 hours of hatch markedly reduces faecal shedding and colonisation with the foodborne pathogen Salmonella enterica serovar Typhimurium (ST4/74). Administration route has minimal effect on the protection conferred with fewer birds in transplant groups shown to shed ST4/74 in the faeces compared to PBS-gavaged control birds. Analysis of the microbiome following transplantation demonstrated that the relative abundance of the anti-inflammatory bacterium Faecalibacterium prausnitzii was significantly higher in CMT groups compared to PBS controls. The presence of F. prausnitzii was also shown to increase in PBS-challenged birds compared to unchallenged birds potentially indicating a role of this bacterium in limiting Salmonella infections. ConclusionsThis study highlights the efficacy of using microbiome transplants as a means to reduce colonisation and shedding of Salmonella in chickens. Effective protection can be conferred during the first few days of a chicks life regardless of time point and traditional hatchery delivery systems are sufficient to alter the microbiome and transfer donor material. Early microbiota intervention in chickens is a promising route of pathogen control in broiler flocks in the fight to control food-borne outbreaks in the human population.

microbiology↗