Global compositional and functional states of the human gut microbiome in health and disease.

The human gut microbiota is of increasing interest, with metagenomics a key tool for analyzing bacterial diversity and functionality in health and disease. Despite increasing efforts to expand microbial gene catalogs and an increasing number of metagenome-assembled genomes, there have been few pan-metagenomic association studies and in-depth functional analyses across different geographies and diseases. Here, we explored 6014 human gut metagenome samples across 19 countries and 23 diseases by performing compositional, functional cluster, and integrative analyses.

Design and Discovery of a Potent and Selective Inhibitor of Integrin αvβ1.

Selective inhibition of the RGD (Arg-Gly-Asp) integrin αvβ1 has been recently identified as an attractive therapeutic approach for the treatment of liver fibrosis given its function, target expression, and safety profile. Our identification of a non-RGD small molecule lead followed by focused, systematic changes to the core structure utilizing a crystal structure, modeling, and a tractable synthetic approach resulted in the identification of a potent small molecule exhibiting a remarkable affinity for αvβ1 relative to several other integrin isoforms measured. Azabenzimidazolone demonstrated antifibrotic efficacy in an rat liver fibrosis model and represents a tool compound capable of further exploring the biological consequences of selective αvβ1 inhibition.

Genome-scale metabolic modelling of the human gut microbiome reveals changes in the glyoxylate and dicarboxylate metabolism in metabolic disorders.

The human gut microbiome has been associated with metabolic disorders including obesity, type 2 diabetes, and atherosclerosis. Understanding the contribution of microbiome metabolic changes is important for elucidating the role of gut bacteria in regulating metabolism. We used available metagenomics data from these metabolic disorders, together with genome-scale metabolic modeling of key bacteria in the individual and community-level to investigate the mechanistic role of the gut microbiome in metabolic diseases.

A general pattern of trade-offs between ecosystem resistance and resilience to tropical cyclones.

Tropical cyclones drive coastal ecosystem dynamics, and their frequency, intensity, and spatial distribution are predicted to shift with climate change. Patterns of resistance and resilience were synthesized for 4138 ecosystem time series from = 26 storms occurring between 1985 and 2018 in the Northern Hemisphere to predict how coastal ecosystems will respond to future disturbance regimes. Data were grouped by ecosystems (fresh water, salt water, terrestrial, and wetland) and response categories (biogeochemistry, hydrography, mobile biota, sedentary fauna, and vascular plants).