Microbe-Metabolite Associations Linked to the Rebounding Murine Gut Microbiome Postcolonization with Vancomycin-Resistant Enterococcus faecium

Vancomycin-resistant Enterococcus faecium (VREfm) is an emerging antibiotic-resistant pathogen. Strain-level investigations are beginning to reveal the molecular mechanisms used by VREfm to colonize regions of the human bowel. However, the role of commensal bacteria during VREfm colonization, in particular following antibiotic treatment, remains largely unknown. We employed amplicon 16S rRNA gene sequencing and metabolomics in a murine model system to try and investigate functional roles of the gut microbiome during VREfm colonization. First-order taxonomic shifts between Bacteroidetes and Tenericutes within the gut microbial community composition were detected both in response to pretreatment using ceftriaxone and to subsequent VREfm challenge. Using neural networking approaches to find cooccurrence profiles of bacteria and metabolites, we detected key metabolome features associated with butyric acid during and after VREfm colonization. These metabolite features were associated with Bacteroides, indicative of a transition toward a preantibiotic naive microbiome. This study shows the impacts of antibiotics on the gut ecosystem and the progression of the microbiome in response to colonization with VREfm. Our results offer insights toward identifying potential nonantibiotic alternatives to eliminate VREfm through metabolic reengineering to preferentially select for Bacteroides IMPORTANCE This study demonstrates the importance and power of linking bacterial composition profiling with metabolomics to find the interactions between commensal gut bacteria and a specific pathogen. Knowledge from this research will inform gut microbiome engineering strategies, with the aim of translating observations from animal models to human-relevant therapeutic applications

The nitrate time bomb : a numerical way to investigate nitrate storage and lag time in the unsaturated zone

Nitrate pollution in groundwater, which is mainly from agricultural activities, remains an international problem. It threatens the environment, economics and human health. There is a rising trend in nitrate concentrations in many UK groundwater bodies. Research has shown it can take decades for leached nitrate from the soil to discharge into groundwater and surface water due to the ‘store’ of nitrate and its potentially long travel time in the unsaturated and saturated zones. However, this time lag is rarely considered in current water nitrate management and policy development. The aim of this study was to develop a catchment-scale integrated numerical method to investigate the nitrate lag time in the groundwater system, and the Eden Valley, UK, was selected as a case study area. The method involves three models, namely the nitrate time bomb—a process-based model to simulate the nitrate transport in the unsaturated zone (USZ), GISGroundwater—a GISGroundwater flow model, and N-FM—a model to simulate the nitrate transport in the saturated zone. This study answers the scientific questions of when the nitrate currently in the groundwater was loaded into the unsaturated zones and eventually reached the water table; is the rising groundwater nitrate concentration in the study area caused by historic nitrate load; what caused the uneven distribution of groundwater nitrate concentration in the study area; and whether the historic peak nitrate loading has reached the water table in the area. The groundwater nitrate in the area was mainly from the 1980s to 2000s, whilst the groundwater nitrate in most of the source protection zones leached into the system during 1940s–1970s; the large and spatially variable thickness of the USZ is one of the major reasons for unevenly distributed groundwater nitrate concentrations in the study area; the peak nitrate loading around 1983 has affected most of the study area. For areas around the Bowscar, Beacon Edge, Low Plains, Nord Vue, Dale Springs, Gamblesby, Bankwood Springs, and Cliburn, the peak nitrate loading will arrive at the water table in the next 34 years; statistical analysis shows that 8.7 % of the Penrith Sandstone and 7.3 % of the St Bees Sandstone have not been affected by peak nitrate. This research can improve the scientific understanding of nitrate processes in the groundwater system and support the effective management of groundwater nitrate pollution for the study area. With a limited number of parameters, the method and models developed in this study are readily transferable to other areas

A importância da ultra-sonografia transvulvar na avaliação de parâmetros anatômicos relevantes no tratamento de mulheres com incontinência urinária de esforço The value of transvulvar ultrasonography in the assessment of major anatomical parameters in the management of female stress urinary incontinence

OBJETIVO: Descrever a importância da ultra-sonografia transvulvar na avaliação das diferenças anatômicas induzidas pelas cirurgias de sling de fáscia lata e tension-free vaginal tape. MATERIAIS E MÉTODOS: Quarenta mulheres com incontinência urinária de esforço, com idades entre 30 e 60 anos, foram tratadas por sling de fáscia lata (20 pacientes) ou tension-free vaginal tape (20 pacientes). A ultra-sonografia transvulvar da junção uretrovesical e da uretra proximal foi a principal ferramenta de investigação pré- e pós-operatória. Os parâmetros estudados foram: distância vertical e distância horizontal da junção uretrovesical, distância pubouretral e comprimento da uretra proximal. RESULTADOS: A distância vertical da junção uretrovesical não variou significativamente após a sling de fáscia lata (p > 0,10). A distância pubouretral e a uretra proximal tornaram-se menores (p < 0,003) e a distância horizontal da junção uretrovesical tornou-se menor só no repouso (p = 0,03) após a sling de fáscia lata. A tension-free vaginal tape diminuiu o deslocamento vertical da junção uretrovesical (p = 0,0005) e o comprimento da uretra proximal (p = 0,02). CONCLUSÃO: A ultra-sonografia transvulvar foi fundamental para documentar que as cirurgias de sling de fáscia lata e tension-free vaginal tape alongam a uretra proximal, sendo a sling de fáscia lata de forma mais eficaz. A sling de fáscia lata enfoca a diminuição da distância pubouretral e a tension-free vaginal tape, o deslocamento vertical da junção uretrovesical.<br>OBJECTIVE: The aim of this study was to describe the role of transvulvar ultrasonography in the assessment of anatomical changes following fascia lata sling or tension-free vaginal tape procedures. MATERIALS AND METHODS: Forty women in the age range between 30 and 60 years had fascia lata sling (20 patients) or tension-free vaginal tape (20 patients) placement for treating stress urinary incontinence. Transvulvar ultrasonography was utilized, both pre- and post-operatively, as the main investigational tool in these cases for evaluating the urethrovesical junction vertical and horizontal distances, pubo-urethral distance and proximal urethra length. RESULTS: The urethrovesical junction vertical distance did not vary significantly after the fascia lata sling surgery (p > 0.10). Both the pubo-urethral distance and the proximal urethra length became shorter (p < 0.003), and the urethrovesical junction horizontal distance was reduced only at rest (p = 0.03). The tension-free vaginal tape procedure resulted in a reduction of the urethrovesical junction vertical distance (p = 0.0005) and of the proximal urethra length (p = 0.02). CONCLUSION: Transvulvar ultrasonography was of utmost importance in the demonstration that both the fascia lata sling and tension-free vaginal tape surgical procedures elongate the proximal urethra, even though the fascia lata sling technique does it more effectively. The fascia lata sling technique is more focused on shortening the pubo-urethral distance, and the tension-free vaginal tape, on the correction of the vertical displacement of the urethrovesical junction