Biology subjects

Rothman, J. A.

Publications and source records attributed to Rothman, J. A..

4 recordsLinked to original sources

bioRxiv2024

Salivary metabolomics in the family environment: A large-scale study investigating oral metabolomes in children and their parental caregivers

Human metabolism is complex and dynamic, and is impacted by genetics, diet, health, and countless inputs from the environment. Beyond the genetics shared by family members, cohabitation leads to shared microbial and environmental exposures. Furthermore, metabolism is affected by factors such as inflammation, environmental tobacco smoke (ETS) exposure, metabolic regulation, and exposure to heavy metals. Metabolomics represents a useful analytical method to assay the metabolism of individuals to find potential biomarkers for metabolic conditions that may not be phenotypically obvious or represent unknown physiological processes. As such, we applied untargeted LC-MS metabolomics to archived saliva samples from a racially diverse group of elementary school-aged children and their caregivers collected during the "90-month" assessment of the Family Life Project. We assayed a total of 1,425 saliva samples of which 1,344 were paired into 672 caregiver/child dyads. We compared the metabolomes of children (N = 719) and caregivers (N = 706) within and between homes, performed population-wide "metabotype" analyses, and measured associations between metabolites and salivary biomeasures of inflammation, antioxidant potential, ETS exposure, metabolic regulation, and heavy metals. Dyadic analyses revealed that children and their caregivers have largely similar salivary metabolomes. Although there were differences between the dyads at the individual levels of analysis, dyad explained most (62%) of the metabolome variation. At a population level of analysis, our data clustered into two large groups, indicating that people likely share most of their metabolomes, but that there are distinct "metabotypes" across large sample sets. Lastly, individual differences in several metabolites - which were putative oxidative damage-associated or pathological markers - were significantly correlated with salivary measures indexing inflammation, antioxidant potential, ETS exposure, metabolic regulation, and heavy metals. Implications of the effects of family environment on metabolomic variation at the population, dyadic, and individual levels of analyses for health and human development are discussed.

systems biology↗

bioRxiv2022

Sequencing and variant detection of eight abundant plant-infecting tobamoviruses across Southern California wastewater.

Tobamoviruses are agriculturally-relevant viruses that cause crop losses and have infected plants in many regions of the world. These viruses are frequently found in municipal wastewater - likely coming from human diet and industrial waste across wastewater catchment areas. As part of a large wastewater-based epidemiology study across Southern California, we analyzed RNA sequence data from 275 influent wastewater samples obtained from eight wastewater treatment plants with a catchment area of approximately 16 million people from July 2020 - August 2021. We assembled 1,083 high-quality genomes, enumerated viral sequencing reads, and detected thousands of single nucleotide variants from eight common tobamoviruses: Bell Pepper Mottle Virus, Cucumber Green Mottle Mosaic Virus, Pepper Mild Mottle Virus, Tobacco Mild Green Mosaic Virus, Tomato Brown Rugose Fruit Virus, Tomato Mosaic Virus, Tomato Mottle Mosaic Virus, and Tropical Soda Apple Mosaic Virus. We show that single nucleotide variants had amino acid-altering consequences along with synonymous mutations, which represents potential evolution with functional consequences in genomes of these viruses. Our study shows the importance of wastewater sequencing to monitor the genomic diversity of these plant-infecting viruses, and we suggest that our data could be used to continue tracking the genomic variability of such pathogens. ImportanceDiseases caused by viruses in the genus Tobamovirus cause crop losses around the world. As with other viruses, mutation occurring in the virus genomes can have functional consequences and may alter viral infectivity. Many of these plant-infecting viruses have been found in wastewater, likely coming from human consumption of infected plants and produce. By sequencing RNA extracted from influent wastewater obtained from eight wastewater treatment plants in Southern California, we assembled high-quality viral genomes and detected thousands of single nucleotide variants from eight tobamoviruses. Our study shows that Tobamovirus genomes vary at many positions, which may have important consequences to viral host switching and the detection of these viruses by agricultural or environmental scientists.

microbiology↗

bioRxiv2022

Longitudinal metatranscriptomic sequencing of Southern California wastewater representing 16 million people from August 2020-21 reveals widespread transcription of antibiotic resistance genes.

Municipal wastewater provides a representative sample of human fecal waste across a catchment area and contains a wide diversity of microbes. Sequencing wastewater samples provides information about human-associated and medically-important microbial populations, and may be useful to assay disease prevalence and antimicrobial resistance (AMR). Here, we present a study in which we used untargeted metatranscriptomic sequencing on RNA extracted from 275 sewage influent samples obtained from eight wastewater treatment plants (WTPs) representing approximately 16 million people in Southern California between August 2020 - August 2021. We characterized bacterial and viral transcripts, assessed metabolic pathway activity, and identified over 2,000 AMR genes/variants across all samples. Because we did not deplete ribosomal RNA, we have a unique window into AMR carried as ribosomal mutants. We show that AMR diversity varied between WTPs and that the relative abundance of many individual AMR genes/variants increased over time and may be connected to antibiotic use during the COVID-19 pandemic. Similarly, we detected transcripts mapping to human pathogenic bacteria and viruses suggesting RNA sequencing is a powerful tool for wastewater-based epidemiology and that there are geographical signatures to microbial transcription. We captured the transcription of gene pathways common to bacterial cell processes, including central carbon metabolism, nucleotide synthesis/salvage, and amino acid biosynthesis. We also posit that due to the ubiquity of many viruses and bacteria in wastewater, new biological targets for microbial water quality assessment can be developed. To the best of our knowledge, our study provides the most complete longitudinal metatranscriptomic analysis of a large populations wastewater to date and demonstrates our ability to monitor the presence and activity of microbes in complex samples. By sequencing RNA, we can track the relative abundance of expressed AMR genes/variants and metabolic pathways, increasing our understanding of AMR activity across large human populations and sewer sheds.

microbiology↗

bioRxiv2020

The direct and indirect effects of environmental toxicants on the health of bumble bees and their microbiomes.

Bumble bees (Bombus spp.) are important and widespread insect pollinators, but the act of foraging on flowers can expose them to harmful pesticides and environmental chemicals such as oxidizers and heavy metals. How these compounds directly influence bee survival and indirectly affect bee health via the gut microbiome is largely unknown. As the toxins and toxicants in floral nectar and pollen take many forms, we explored the genomes of core bumblebee microbes (Using RAST) for their potential to detoxify cadmium, copper, selenium, the neonicotinoid pesticide imidacloprid, and hydrogen peroxide - which have all been identified in floral nectar and pollen. We then exposed Bombus impatiens workers to varying concentrations of these chemicals spiked into their diet and identified the direct effects on bee survival. Using field realistic doses, we further explored indirect effects on bee microbiomes. We found multiple genes in core gut microbes that have the potential to aid in detoxifying harmful chemicals. We also found that while the chemicals are largely toxic at levels within and above field-realistic concentrations, the field-realistic concentrations - except for imidacloprid - altered the composition of the bee microbiome, potentially causing gut dysbiosis. Overall, our study shows that environmental chemicals found in floral nectar and pollen can directly cause bee mortality, and at field-realistic levels, likely have indirect, deleterious effects on bee health via their influence on the bee microbiome.

ecology↗