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Davis, E. W.

Publications and source records attributed to Davis, E. W..

6 recordsLinked to original sources

Polycyclic aromatic hydrocarbons, gut microbiome composition, impulsivity, and attention covary in a human cohort

Polycyclic aromatic hydrocarbons (PAHs) are pervasive environmental pollutants linked to adverse neurobehavioral outcomes, yet the biological pathways coupling exposure to behavior are poorly defined. The gut microbiome is both sensitive to PAH exposure and a modulator of central nervous system function, suggesting it may mediate how PAH exposure influences neurobehavior. We tested whether PAH exposure, gut microbiome composition, and neurobehavioral function covary in a statewide sample of 34 adults stratified into high-impulsivity/poor-attention (HH) and low-impulsivity/fast-attention (LL) groups. Participants provided fecal samples for 16S rRNA profiling and wore silicone wristbands for 30 days to passively sample PAH exposure. Higher PAH exposure associated with HH group membership in a sex-dependent manner, with the largest elevations among HH males. At the community level, PAH exposure profiles correlated with microbiome dissimilarity, and HH membership associated with increased alpha-diversity and altered community composition relative to LL members. At the taxon level, 21 genera were significantly associated with 14 PAH compounds (FDR < 0.1). No individual genera were significantly associated with neurobehavioral group after multiple testing correction. Nevertheless, cross-referencing PAH-responsive genera (FDR < 0.1) against those with nominal neurobehavioral associations (p < 0.05) identified two candidate genera, Hydrogenoanaerobacterium and Methanobrevibacter, whose abundance covaries with both PAH exposure and neurobehavioral phenotype. Both have been independently linked to cognitive or neurological outcomes in prior work. These findings support a three-way relationship among environmental chemical exposure, gut microbiome composition, and neurobehavioral function, establishing an empirical foundation for testing microbiome-mediated links between PAH exposure and neurobehavioral outcomes. IMPORTANCEPAH exposure is widespread and associates with impulsivity and attention problems, but how exposure translates into neurobehavioral risk is unclear. The gut microbiome is a plausible intermediary: gut microbes biotransform environmental chemicals and produce metabolites that influence brain function. In a statewide adult cohort, we show that higher PAH exposure tracks with greater impulsivity and poorer attention in a sex-dependent manner, and that both PAH exposure and neurobehavioral phenotype associate with distinct gut microbiome features at the community and taxon levels. We identify candidate genera at the intersection of PAH exposure and neurobehavioral group whose biology independently implicates them in cognitive and neurological function. By demonstrating that all three domains covary within a single human cohort, this work moves beyond pairwise associations to identify candidate microbial intermediaries for mechanistic investigation. Defining the microbiome constituents that respond to PAH exposure and co-associate with neurobehavioral phenotypes creates opportunities to test microbiome-targeted or exposure-reduction strategies for mitigating PAH-related neurobehavioral impacts.

microbiology↗

Rapid and sensitive detection of genome contamination at scale with FCS-GX

Assembled genome sequences are being generated at an exponential rate. Here we present FCS-GX, part of NCBIs Foreign Contamination Screen (FCS) tool suite, optimized to identify and remove contaminant sequences in new genomes. FCS-GX screens most genomes in 0.1-10 minutes. Testing FCS-GX on artificially fragmented genomes demonstrates sensitivity >95% for diverse contaminant species and specificity >99.93%. We used FCS-GX to screen 1.6 million GenBank assemblies and identified 36.8 Gbp of contamination (0.16% of total bases), with half from 161 assemblies. We updated assemblies in NCBI RefSeq to reduce detected contamination to 0.01% of bases. FCS-GX is available at https://github.com/ncbi/fcs/.

bioinformatics↗

Age and micronutrient effects on the microbiome in a mouse model of zinc depletion and supplementation

Older adult populations are at risk for elevated zinc deficiency, which may predispose them to immune dysfunction and age-related chronic inflammation that drives myriad diseases and disorders. Recent work also implicates the gut microbiome in the onset and severity of age-related inflammation, indicating that dietary zinc status and the gut microbiome may interact to impact age-related host immunity. We hypothesize that age-related alterations in the gut microbiome contribute to the demonstrated zinc deficits in host zinc levels and increased inflammation. We tested this hypothesis with a multifactor two-part study design in a C57BL/6 mouse model. The two studies included young (2 month old) and aged (24 month old) mice fed either (1) a zinc adequate or zinc supplemented diet, or (2) a zinc adequate or marginal zinc deficient diet, respectively. Overall microbiome composition did not significantly change with zinc status; beta diversity was driven almost exclusively by age effects. Microbiome differences due to age are evident at all taxonomic levels, with more than half of all taxonomic units significantly different at each. Furthermore, we found 150 out of 186 genera were significantly different between the two age groups, with Bacteriodes and Parabacteroides being the primary components of young and old mice, respectively. These data suggest that modulating individual micronutrient concentrations does not lead to comprehensive microbiome shifts, but rather affects specific components of the gut microbiome. However, a phylogenetic agglomeration technique (ClaaTU) revealed phylogenetic clades of microbiota that respond to modulation of dietary zinc status in an age-dependent manner. Collectively, these results suggest that there exists a complex interplay between host age, gut microbiome composition, and dietary zinc status.

microbiology↗

Differences in the regulatory strategies of marine oligotrophs and copiotrophs reflect differences in motility

Aquatic bacteria frequently are divided into lifestyle categories oligotroph or copiotroph. Oligotrophs have proportionately fewer transcriptional regulatory genes than copiotrophs and are generally non-motile/chemotactic. We hypothesized that the absence of chemotaxis/motility in oligotrophs prevents them from occupying nutrient patches long enough to benefit from transcriptional regulation. We first confirmed that marine oligotrophs are generally reduced in genes for transcriptional regulation and motility/chemotaxis. Next, using a non-motile oligotroph (Ca. Pelagibacter st. HTCC7211), a motile copiotroph (Alteromonas macleodii st. HOT1A3), and [14C]L-alanine, we confirmed that L-alanine catabolism is not transcriptionally regulated in HTCC7211 but is in HOT1A3. We then found that HOT1A3 took 2.5-4 min to initiate L-alanine oxidation at patch L-alanine concentrations, compared to <30s for HTCC7211. By modeling cell trajectories, we predicted that, in most scenarios, non-motile cells spend <2 min in patches, compared to >4 mins for chemotactic/motile cells. Thus, the time necessary for transcriptional regulation to initiate prevents transcriptional regulation from being beneficial for non-motile oligotrophs. This is supported by a mechanistic model we developed, which predicted that HTCC7211 cells with transcriptional regulation of L-alanine metabolism would produce 12% of their standing ATP stock upon encountering an L-alanine patch, compared to 880% in HTCC7211 cells without transcriptional regulation.

microbiology↗

Biochemical Barriers on the Path to Ocean Anoxia?

The kinetics of microbial respiration suggest that, if excess organic matter is present, oxygen should fall to nanomolar levels, in the range of the Michaelis-Menten constants (Km). Yet even in many biologically productive coastal regions, lowest observed O2 concentrations often remain several orders of magnitude higher than respiratory Km values. We propose the Hypoxic Barrier Hypothesis (HBH) to explain this apparent discrepancy. The HBH postulates that oxidative enzymes involved in organic matter catabolism are kinetically limited by O2 at concentrations far higher than the thresholds for respiration. We found support for the HBH in a meta-analysis of 1137 O2 Km values reported in the literature: the median value for terminal respiratory oxidases was 350 nM, but for other oxidase types the median value was 67 M. The HBH directs our attention to the kinetic properties of an important class of oxygen-dependent reactions that could help explain the trajectories of ocean ecosystems experiencing O2 stress. IMPORTANCEDeclining ocean oxygen associated with global warming and climate change is impacting marine ecosystems across scales from microscopic planktonic communities to global fisheries. We report a fundamental dichotomy in the affinity of enzymes for oxygen. The importance of this observation has yet to be fully assessed, but it is predicted to impact the rate at which organic matter is oxidized in hypoxic ecosystems, and the types of organic matter that accumulate. Competition between intracellular enzymes for oxygen may also have impacted microbial strategies of adaptation to suboxia.

microbiology↗

Unexpected distribution of the 4-formylaminooxyvinylglycine (FVG) biosynthetic pathway in Pseudomonas and beyond

The biological herbicide and antibiotic 4-formylaminooxyvinylglycine (FVG) was originally isolated from several rhizosphere-associated strains of Pseudomonas fluorescens. Biosynthesis of FVG is dependent on the gvg biosynthetic gene cluster in P. fluorescens. In this investigation, we used comparative genomics to identify strains with the genetic potential to produce FVG due to presence of a gvg gene cluster. These strains primarily belong to two groups of Pseudomonas, P. fluorescens and P. syringae, however, a few strains with the gvg cluster were found outside of Pseudomonas. Mass spectrometry confirmed that all tested strains of the P. fluorescens species group produced FVG. However, P. syringae strains did not produce FVG under standard conditions. Several lines of evidence regarding the transmission of the gvg cluster including a robust phylogenetic analysis suggest that it was introduced multiple times through horizontal gene transfer within the Pseudomonas lineage as well as in select lineages of Thiomonas, Burkholderia and Pantoea. Together, these data broaden our understanding of the evolution and diversity of FVG biosynthesis. In the course of this investigation, additional gene clusters containing only a subset of the genes required to produce FVG were identified in a broad range of bacteria, including many non-pseudomonads.

microbiology↗