Biology subjects

Creek, D.

Publications and source records attributed to Creek, D..

3 recordsLinked to original sources

bioRxiv2022

Dietary fibre controls blood pressure and cardiovascular risk by lowering large intestinal pH and activating the proton-sensing receptor GPR65

High blood pressure (BP) is the most common cause of death globally, due to increasing the risk of cardiovascular diseases. Dietary fiber regulates BP through gut microbial production of acidic metabolites known as short-chain fatty acids (SCFAs). The specific mechanisms of how SCFAs regulate BP are still emerging. In a phenome-wide association study, we identified that the proton-sensing G-protein-coupled receptor GPR65 gene is associated with hypertension and its associated end-organ damage phenotypes. We hypothesized that acidic metabolites produced from the gut microbiota may activate GPR65, thus conferring BP regulating effects. We found that dietary fiber levels determined the luminal and interstitial tissue pH in the large intestine through production of SCFAs by the gut microbiota. We identified that low pH produced by high fiber intake, acting via GPR65 signaling, increased cAMP production and phosphorylation of CREB, and restricted the production of hypertension-promoting inflammatory cytokines by CD8+ T cells. Gpr65-/- mice spontaneously developed higher BP, cardiac and renal hypertrophy and fibrosis. We showed that the benefits of a diet high in fiber, which prevented hypertension and associated end-organ damage, were decreased in Gpr65-/- mice. Finally, adoptive transfers revealed that GPR65 deficiency in CD8+ T cells causally explained this phenotype. In conclusion, we showed that pH sensing by GPR65 in CD8+ T cells mediates much of the cardiovascular benefits of dietary fiber. pH sensing represents a novel gene-by-environment interaction of gut microbiota-to-host biological effects and may form the basis for new therapeutic strategies for hypertension.

molecular biology↗

bioRxiv2022

Physiological trait networks enhance understanding of crop growth and water use in contrasting environments

Plant function arises from a complex network of structural and physiological traits. Explicit representation of these traits, as well as their connections with other biophysical processes, is required to advance our understanding of plant-soil-climate interactions. We used the Terrestrial Regional Ecosystem Exchange Simulator (TREES) to evaluate physiological trait networks in maize. Net primary productivity (NPP) and grain yield were simulated across five contrasting climate scenarios. Simulations achieving high NPP and grain yield in high precipitation environments featured trait networks conferring high water use strategies: deep roots, high stomatal conductance at low water potential ("risky" stomatal regulation), high xylem hydraulic conductivity, and high maximal leaf area index. In contrast, high NPP and grain yield was achieved in dry environments with low late-season precipitation via water conserving trait networks: deep roots, high embolism resistance, and low stomatal conductance at low leaf water potential ("conservative" stomatal regulation). We suggest that our approach, which allows for the simultaneous evaluation of physiological traits and their interactions (i.e., networks), has potential to improve crop growth predictions in different environments. In contrast, evaluating single traits in isolation of other coordinated traits does not appear to be an effective strategy for predicting plant performance. Summary statementOur process-based model uncovered two beneficial but contrasting trait networks for maize which can be understood by their integrated effect on water use/conservation. Modification of multiple, physiologically aligned, traits were required to bring about meaningful improvements in NPP and yield.

plant biology↗

bioRxiv2022

Maternal diet and gut microbiota influence predisposition to cardiovascular disease in the offspring

Cardiovascular disease is one of the most significant causes of death globally, especially in regions where unhealthy diets are prevalent and dietary fibre intake is low.1,2 Fibre, particularly prebiotic types that feed gut microbes, is essential for maintaining healthy gut microbial ecosystems.3 One assumption has been that cardiovascular health relates directly to lifestyle choices in adult life. Here, we show in mice that some of these benefits operate from the prenatal stage and relate to the diet and gut microbiome of the mother. Intake of fibre during pregnancy shaped the mothers gut microbiome, which had a lasting founding effect on the offsprings microbial composition and function. Maternal fibre intake during pregnancy significantly changed the cardiac cellular and molecular landscape in the offspring, protecting them against the development of cardiac hypertrophy, remodelling, and inflammation. These suggest a role for foetal exposure to maternal-derived gut microbial metabolites, which are known to cross the placenta and drive epigenetic changes. Maternal fibre intake led to foetal epigenetic reprogramming of the atrial natriuretic peptide gene (Nppa), protective against heart failure. These results underscore the importance of dietary intake and the gut microbiome of the mother during pregnancy for cardiovascular disease in the offspring.

microbiology↗