Gut microbial communities can respond to antibiotic perturbations by rapidly altering their taxonomic and functional composition. However, little is known about the strain-level processes that drive this collective response. Here, we characterize the gut microbiome of a single individual at high temporal and genetic resolution through a period of health, disease, antibiotic treatment, and recovery. We used deep, linked-read metagenomic sequencing to track the longitudinal trajectories of thousands of single nucleotide variants within 36 species, which allowed us to contrast these genetic dynamics with the ecological fluctuations at the species level. We found that antibiotics can drive rapid shifts in the genetic composition of individual species, often involving incomplete genome-wide sweeps of pre-existing variants. These genetic changes were frequently observed in species without obvious changes in species abundance, emphasizing the importance of monitoring diversity below the species level. We also found that many sweeping variants quickly reverted to their baseline levels once antibiotic treatment had concluded, demonstrating that the ecological resilience of the microbiota can sometimes extend all the way down to the genetic level. Our results provide new insights into the population genetic forces that shape individual microbiomes on therapeutically relevant timescales, with potential implications for personalized health and disease.

Background Lignans in plant foods are metabolized by gut bacteria to the enterolignans, enterodiol (END) and enterolactone (ENL). Enterolignans have biologic activities important to the prevention of cancer and chronic diseases. We examined the composition of the gut microbial community (GMC) as a contributor to human enterolignan exposure. Methods We evaluated the association between the GMC in stool, urinary enterolignan excretion, and diet from a 3-day food record in 115 premenopausal (ages 40–45 y) women in the United States. Urinary enterolignans were measured using GC/MS. The GMC was evaluated using 454 pyrosequencing of the 16S rRNA gene. Sequences were aligned in SILVA (www.arb-silva.de). Operational taxonomic units (OTU) were identified at 97% sequence similarity. Taxonomic classification was performed and alpha and beta diversity in relationship to ENL production were assessed. Multivariate analysis and regression were used to model the association between enterolignan excretion and the GMC. Bacteria associated with ENL production were identified using univariate analysis and ridge regression. Results After adjusting for dietary fiber intake and adiposity, we found a significant positive association between ENL excretion and either the GMC (p=0.0007), or the diversity of the GMC (p=0.01). The GMC associated with high ENL production was distinct (UNIFRAC, p<0.003, MRPP) and enriched in Moryella spp., Acetanaerobacterium spp., Fastidiosipila spp., and Streptobacillus spp. Conclusion Diversity and composition of the GMC are associated with increased human exposure to enterolignans. Impact Differences in gut microbial diversity and composition explain variation in gut metabolic processes that impact environmental exposures and influences human health.

Gut microbial communities can respond to antibiotic perturbations by rapidly altering their taxonomic and functional composition. However, little is known about the strain-level processes that drive this collective response. Here we characterize the gut microbiome of a single individual at high temporal and genetic resolution through a period of health, disease, antibiotic treatment, and recovery. We used deep, linked-read metagenomic sequencing to track the longitudinal dynamics of thousands of single nucleotide variants within 36 species, which allowed us to contrast these genetic dynamics with the ecological fluctuations at the species level. We find that antibiotics can drive rapid shifts in the genetic composition of individual species, often involving incomplete genome-wide sweeps of pre-existing variants. Interestingly, genetic changes frequently occur in species without obvious changes in relative species abundance, emphasizing the importance of monitoring diversity below the species level. Our results provide new insights into the population genetic forces that shape individual microbiomes on therapeutically relevant timescales, with potential implications for personalized health and disease.

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With two genomes in the same organism, interspecific hybrids have unique fitness opportunities and costs. In both plants and yeasts, wild, pathogenic, and domesticated hybrids may eliminate portions of one parental genome, a phenomenon known as loss of heterozygosity (LOH). Laboratory evolution of hybrid yeast recapitulates these results, with LOH occurring in just a few hundred generations of propagation. In this study, we systematically looked for alleles that are beneficial when lost in order to determine how prevalent this mode of adaptation may be and to determine candidate loci that might underlie the benefits of larger-scale chromosome rearrangements. These aims were accomplished by mating Saccharomyces uvarum with the S. cerevisiae deletion collection to create hybrids such that each nonessential S. cerevisiae allele is deleted. Competitive fitness assays of these pooled, barcoded, hemizygous strains, and accompanying controls, revealed a large number of loci for which LOH is beneficial. We found that the fitness effects of hemizygosity are dependent on the species context, the selective environment, and the species origin of the deleted allele. Further, we found that hybrids have a wider distribution of fitness consequences versus matched S. cerevisiae hemizygous diploids. Our results suggest that LOH can be a successful strategy for adaptation of hybrids to new environments, and we identify candidate loci that drive the chromosomal rearrangements observed in evolution of yeast hybrids.

BackgroundIdentify variables associated with intrapartum epidural use.MethodsOdds ratios were calculated to quantify associations between selected variables and epidural use using a population-based case-control study of Washington State birth certificate data from 2009.ResultsNon-Whites had 10 - 45% lower odds of epidural use relative to Whites. Foreign-born women had 25 - 45% lower odds of epidural use compared to their US-born counterparts, except for Asians. Women who smoked or induced labor had higher roughly 2-fold higher odds of epidural use compared with non-smokers or women giving birth spontaneously, respectively. Women without a high school diploma or equivalent had lower odds of epidural use relative to those who graduated. Delivering at perinatal units, rural hospitals, or non-profit hospitals had ~50% lower odds of epidural use compared with secondary/teritiary perinatal units, urban hospitals or for-profit hospitals, respectively. ConclusionSeveral individual and health service-related variables were associated with epidural use. These findings elucidate the clinical relevance of epidural use, and dispariaties in its utilization and in quality of care during delivery.KeywordsEpidural use; Foreign birth; Labor; Racial disparities