GABAergic but not Antidepressant Medications Increase Risk for Clostridioides difficile Infection in a National Cohort of Veterans.

BACKGROUND: Clostridioides difficile infection (CDI) is primarily mediated by alterations in the host gut ecosystem. While antibiotic use is the primary risk factor for CDI, other medications that modulate the gut ecosystem, particularly those targeting the gut-brain axis, could impact CDI risk. This study aimed to investigate the association between recent antidepressant and gamma-aminobutyric acid (GABA)-ergic medication use with CDI risk in a national cohort of United States veterans. METHODS: This was a retrospective case-control study of patients seen in Veterans Health Administration facilities from October 2002 to September 2014. CDI and non-CDI control patients were propensity score matched 1:1 using a maximum caliper of 0.0001. Antidepressant and GABAergic medication use 90 days before cohort inclusion were analyzed for CDI association using bivariable and multivariable logistic regression models. RESULTS: A total of 85 831 patients were included, and 9287 CDI and 9287 control patients were propensity score matched. Antidepressant use overall was not significantly associated with CDI risk (odds ratio [OR], 1.05; 95% CI, 0.98-1.12), although GABAergic medication use was associated with increased risk (OR, 1.81; 95% CI, 1.70-1.92). In multivariable models of individual medications/classes, benzodiazepines had the strongest CDI association (OR, 1.91; 95% CI, 1.77-2.07). SSRIs (OR, 0.88; 95% CI, 0.81-0.95) and bupropion (OR, 0.67; 95% CI, 0.57-0.78) were negatively associated with CDI. CONCLUSIONS: In this national study of veterans, GABAergic medication use was a positive predictor of CDI risk, though antidepressant use was not. Further research is needed to understand biological mechanisms, and confirmatory studies are needed to validate these findings.

Evolution of a CAM anatomy predates the origins of Crassulacean acid metabolism in the Agavoideae (Asparagaceae).

Crassulacean acid metabolism (CAM) is a modified form of photosynthesis that has arisen independently at least 35 times in flowering plants. The occurrence of CAM is often correlated with shifts to arid, semiarid, or epiphytic habits, as well as transitions in leaf morphology (e.g. increased leaf thickness) and anatomy (e.g. increased cell size and packing). We assess shifts between C3 and CAM photosynthesis in the subfamily Agavoideae (Asparagaceae) through phylogenetic analysis of targeted loci captured from the nuclear and chloroplast genomes of over 60 species. Carbon isotope data was used as a proxy for mode of photosynthesis in extant species and ancestral states were estimated on the phylogeny. Ancestral character state mapping suggests three independent origins of CAM in the Agavoideae. CAM species differ from C3 species in climate space and are found to have thicker leaves with densely packed cells. C3 ancestors of CAM species show a predisposition toward CAM-like morphology. Leaf characteristics in the ancestral C3 species may have enabled the repeated evolution of CAM in the Agavoideae subfamily. Anatomical changes, including a tendency toward 3D venation, may have initially arisen in C3 ancestors in response to aridity as a way to increase leaf succulence for water storage.

Gas exchange and leaf anatomy of a C3-CAM hybrid, Yucca gloriosa (Asparagaceae).

While the majority of plants use the typical C3 carbon metabolic pathway, ~6% of angiosperms have adapted to carbon limitation as a result of water stress by employing a modified form of photosynthesis known as Crassulacean acid metabolism (CAM). CAM plants concentrate carbon in the cells by temporally separating atmospheric carbon acquisition from fixation into carbohydrates. CAM has been studied for decades, but the evolutionary progression from C3 to CAM remains obscure. In order to better understand the morphological and physiological characteristics associated with CAM photosynthesis, phenotypic variation was assessed in Yucca aloifolia, a CAM species, Yucca filamentosa, a C3 species, and Yucca gloriosa, a hybrid species derived from these two yuccas exhibiting intermediate C3-CAM characteristics. Gas exchange, titratable leaf acidity, and leaf anatomical traits of all three species were assayed in a common garden under well-watered and drought-stressed conditions. Yucca gloriosa showed intermediate phenotypes for nearly all traits measured, including the ability to acquire carbon at night. Using the variation found among individuals of all three species, correlations between traits were assessed to better understand how leaf anatomy and CAM physiology are related. Yucca gloriosa may be constrained by a number of traits which prevent it from using CAM to as high a degree as Y. aloifolia. The intermediate nature of Y. gloriosa makes it a promising system in which to study the evolution of CAM.