Search bioRxiv⌕ Search

Biology subjects

Herd, P.

Publications and source records attributed to Herd, P..

3 recordsLinked to original sources

Linking interpersonal differences in gut microbiota composition and drug biotransformation activity

Individuals vary widely in their responses to drugs, and growing evidence implicates the gut microbiome as a contributor to this variability. While prior studies show that gut bacteria can metabolize drugs, how differences in microbial community composition influence drug metabolism remains poorly understood. Here, we characterize the biotransformation of 271 drugs by 89 gut microbial communities derived from human donors and preclinical animal models. Over 90% of tested drugs were metabolized by at least one microbiome. We identified 66 drugs exhibiting highly variable metabolism across human-derived microbiomes and several drugs whose biotransformation differed markedly between human and animal microbiomes. To enable prediction of microbiota-mediated drug metabolism, we developed and compared multiple modeling approaches based on metagenomic data. These results, together with the provided data and analytical resources contribute to a better understanding of microbiome-drug interactions and support their future integration into drug discovery, personalized prescription, and therapeutic drug monitoring.

microbiology↗

Resource Profile and User Guide of the Polygenic Index Repository

Polygenic indexes (PGIs) are DNA-based predictors. Their value for research in many scientific disciplines is rapidly growing. As a resource for researchers, we used a consistent methodology to construct PGIs for 47 phenotypes in 11 datasets. To maximize the PGIs prediction accuracies, we constructed them using genome-wide association studies--some of which are novel--from multiple data sources, including 23andMe and UK Biobank. We present a theoretical framework to help interpret analyses involving PGIs. A key insight is that a PGI can be understood as an unbiased but noisy measure of a latent variable we call the "additive SNP factor." Regressions in which the true regressor is the additive SNP factor but the PGI is used as its proxy therefore suffer from errors-in-variables bias. We derive an estimator that corrects for the bias, illustrate the correction, and make a Python tool for implementing it publicly available.

genomics↗

Social relationships, social isolation, and the human gut microbiota

Social relationships shape human health and mortality via behavioral, psychosocial, and physiological mechanisms, including inflammatory and immune responses. Though not tested in human studies, recent primate studies indicate that the gut microbiome may also be a biological mechanism linking relationships to health. Integrating microbiota data into the 60-year-old Wisconsin Longitudinal Study, we found that socialness with family and friends is associated with differences in the human fecal microbiota. Analysis of spouse (N = 94) and sibling pairs (N = 83) further revealed that spouses have more similar microbiota and more bacterial taxa in common than siblings, with no observed differences between sibling and unrelated pairs. These differences held even after accounting for dietary factors. The differences between unrelated individuals and married couples was driven entirely by couples who reported close relationships; there were no differences in similarity between couples reporting somewhat close relationships and unrelated individuals. Moreover, the microbiota of married individuals, compared to those living alone, has greater diversity and richness, with the greatest diversity among couples reporting close relationships, which is notable given decades of research documenting the health benefits of marriage. These results suggest that human interactions, especially sustained, close marital relationships, influence the gut microbiota.

microbiology↗