Biology subjects

Gottel, N.

Publications and source records attributed to Gottel, N..

7 recordsLinked to original sources

bioRxiv2025

Engineering microbial consortia for distributed signal processing

A critical goal in biology is deducing input signals from measurable readouts. Genetic circuits have successfully been designed to respond to specific analytes and produce quantifiable outputs; however, multiplexed signal processing remains challenging. This limitation is partially due to crosstalk, or sensors non-specific responses to unintended signals. While strategies to achieve orthogonality are promising, they are time-intensive and context-dependent. Here, we introduce a new, generalizable approach that leverages microbial consortia to distribute sensory functions and computational methods to disentangle signals. Compartmentalizing sensor circuits within distinct populations simplifies experimental optimization by allowing individual populations to be exchanged without requiring genetic modifications. Our computational pipeline combines mechanistic modeling with machine learning to decode microbial communities unique temporal responses and predict multiple input concentrations. We demonstrated this platforms versatility in a variety of contexts: measuring signals with high crosstalk, detecting antibiotics with natural microbial communities, and quantifying chemicals in hospital sink wastewater. Our findings highlight how combining microbial engineering with computational strategies can produce robust, scalable biosensors for diverse applications.

synthetic biology↗

bioRxiv2021

Synchrony and idiosyncrasy in the gut microbiome of wild primates

Human gut microbial dynamics are highly individualized, making it challenging to link microbiota to health and to design universal microbiome therapies. This individuality is typically attributed to variation in host genetics, diets, environments, and medications, but it could also emerge from fundamental ecological forces that shape microbiota more generally. Here we leverage extensive gut microbial time series from wild baboons--hosts who experience little interindividual dietary and environmental heterogeneity--to test whether gut microbial dynamics are synchronized across hosts or largely idiosyncratic. Despite their shared lifestyles, baboon microbiome dynamics were only weakly synchronized. The strongest synchrony occurred among baboons living in the same social group, likely because group members range over the same habitat and simultaneously encounter the same sources of food and water. However, this synchrony was modest compared to each hosts personalized dynamics. Indeed, host-specific factors, especially host identity, explained 10 times the deviance in longitudinal microbial dynamics, compared to factors shared across hosts. These results contribute to mounting evidence that highly idiosyncratic gut microbiomes are not an artifact of modern human environments, and that synchronizing forces in the gut microbiome (e.g., shared environments, diets, and microbial dispersal) are often not strong enough to overwhelm drivers of microbiome personalization, including host genetics, priority effects, horizontal gene transfer, and functional redundancy.

ecology↗

bioRxiv2019

Manner of death and demographic effects on microbial community composition in organs of the human cadaver

The microbiome serves important functions in human health, and postmortem, the microbial signatures of colonized organ tissue could be useful in helping to predict the manner of death in cases where this information is not known. We surveyed the microbiota (16S rRNA V4 amplicon sequencing) of 265 organ tissue samples including liver, blood, brain, heart, prostate, spleen and uterus from cadavers in Italy, Finland and the United States with confirmed manners of death comprising either accidental death, natural death, homicide, and suicide. Geographic locality (i.e. nationality) had a strong effect on observed microbial composition. Differing PERMANOVA results between unweighted and weighted UniFrac (nearly inverse results) suggest that specific bacteria may be associated with ethnicity and age, but that these differences are negligible when taking into account the relative abundance of bacterial taxa; weighted UniFrac measures suggest that although taxonomic composition may not vary significantly between different manners of death, PMI, or BMI categories, the relative abundance of specific taxa vary significantly. Various tissues exhibit differential associations with bacteria, and prostate and uterus were substantially different compared to other organs. For example, in Italian cadavers, the bacteria MLE1-12 permeated nearly all tissues, except the prostate and uterus. We identified specific bacterial ASVs as biomarkers of either natural or accidental death and suicide, but not for homicide. While the manner of death may have an impact on microbial associations, further investigation under more controlled conditions will be needed to validate whether these associations are predictive in forensic determinations.\n\nImportanceThe utilization of microbial data in the context of forensic investigations holds great promise for the field of forensic science. Identification of taxa that are associated with postmortem interval (PMI), specific manners of death (MOD), or other traits such as age, sex, ethnicity, and nationality may allow investigators to refine the circumstantial details surrounding the death of an individual. In this study we find nationality (geographic location of cadaver) to be a dominant predictor of cadaver microbiome composition. We also identify a number of cadaver-specific traits to be associated with microbial alpha- and beta diversity, as well as bacterial taxa that are differentially associated with these traits.

microbiology↗

bioRxiv2019

Microbial Similarity between Students in a Common Dormitory Environment Reveals the Forensic Potential of Individual Microbial Signatures

The microbiota of the built environment is an amalgamation of both human and environmental sources. While human sources have been examined within single-family households or in public environments, it is unclear what effect a large number of cohabitating people have on the microbial communities of their shared environment. We sampled the public and private spaces of a college dormitory, disentangling individual microbial signatures and their impact on the microbiota of common spaces. We compared multiple methods for marker gene sequence clustering, and found that Minimum Entropy Decomposition (MED) was best able to distinguish between the microbial signatures of different individuals, and was able to uncover more discriminative taxa across all taxonomic groups. Further, weighted UniFrac- and random forest-based graph analyses uncovered two distinct spheres of hand or shoe associated samples. For hand-associated samples, connection between cliques was enriched for hands, implicating them as a primary means of transmission. By contrast, shoe-associated samples were found to be freely interacting, with individual shoes more connected to each other than to the floors they interact with. Individual interactions were highly dynamic, with groups of samples originating from individuals clustering freely with other individuals, while all floor and shoe samples consistently clustered together.\n\nImportanceHumans leave behind a microbial trail, regardless of intention. This may allow for the identification of individuals based on the microbial signatures they shed in built environments. In a shared living environment, these trails intersect, and through interaction with common surfaces may become homogenized, potentially confounding our ability to link individuals to their associated microbiota. We sought to understand the factors that influence the mixing of individual signatures, and how best to process sequencing data to best tease apart these signatures.

ecology↗

bioRxiv2019

The human microbiota is associated with cardiometabolic risk across the epidemiologic transition

Oral and fecal microbial biomarkers have previously been associated with cardiometabolic (CM) risk, however, no comprehensive attempt has been made to explore this association in minority populations or across different geographic regions. We characterized gut- and oral-associated microbiota and CM risk in 655 participants of African-origin, aged 25-45, from Ghana, South Africa, Jamaica, and the United States (US). CM risk was classified using the CM risk cut-points for elevated waist circumference, elevated blood pressure and elevated fasted blood glucose, low high-density lipoprotein (HDL), and elevated triglycerides. Gut-associated bacterial alpha diversity negatively correlated with elevated blood pressure and elevated fasted blood glucose. Similarly, gut bacterial beta diversity was also significantly differentiated by waist circumference, blood pressure, triglyceridemia and HDL-cholesterolemia. Notably, differences in inter- and intra-personal gut microbial diversity were geographic-region specific. Participants meeting the cut-points for 3 out of the 5 CM risk factors were significantly more enriched with Lachnospiraceae, and were significantly depleted of Clostridiaceae, Peptostreptococcaceae, and Prevotella. The predicted relative proportions of the genes involved in the pathways for lipopolysaccharides (LPS) and butyrate synthesis were also significantly differentiated by the CM risk phenotype, whereby genes involved in the butyrate synthesis via lysine, glutarate and 4-aminobutyrate/succinate pathways and LPS synthesis pathway were enriched in participants with greater CM risk. Furthermore, inter-individual oral microbiota diversity was also significantly associated with the CM risk factors, and oral-associated Streptococcus, Prevotella, and Veillonella were enriched in participants with 3 out of the 5 CM risk factors. We demonstrate that in a diverse cohort of African-origin adults, CM risk is significantly associated with reduced microbial diversity, and the enrichment of specific bacterial taxa and predicted functional traits in both gut and oral environments. As well as providing new insights into the associations between the gut and oral microbiota and CM risk, this study also highlights the potential for novel therapeutic discoveries which target the oral and gut microbiota in CM risk.

microbiology↗

bioRxiv2018

Microbial and Metabolic Succession on Common Building Materials Under High Humidity Conditions

Despite considerable efforts to characterize the ecology of bacteria and fungi in the built environment (BE), the metabolic mechanisms underpinning their colonization and successional dynamics remain unclear. Here, we applied bacterial/viral particle counting, qPCR, 16S and ITS rRNA amplicon sequencing, and metabolomics to longitudinally characterize the ecological dynamics of four commonly used building materials maintained at high humidity conditions (~94% RH). We varied the natural inoculum provided to each material by placing them in different occupied spaces, and we wet the surface of half of the samples of each material to simulate a flooding event. As expected, different materials showed different bacterial and viral particle abundance, with wet materials having higher growth rates and lower alpha diversity compared to non-wetted materials. Wetting described the majority of the variance in bacterial, fungal and metabolite structure, and material type only influenced bacterial and metabolic diversity, while location of inoculation was only weakly associated with bacterial and fungal beta diversity. Metabolites indicative of microbial activity were identified, as were those that were native to the surface material. Glucose-phosphate was abundant on all materials (except mold-free gypsum) and was correlated with Enterobacteriaceae, which could indicate a potential bacterial nutrient source. A compound consistent with scopoletin, a plant metabolite with antimicrobial activity, was significantly negatively correlated with Bacillus and positively correlated with Pseudomonas and enriched in medium density fiberboard (MDF) materials. In wet samples, the alkaloids nigragillin and fumigaclavine C, both with antimicrobial properties, were significantly positively correlated with the fungal phylum Ascomycota. Nigragillin, was also negatively correlated with Bacillus and Pseudomonas abundance. Thiabendazole and azoxystrobin (anti-fungal compounds) were highly abundant on mold-resistant gypsum wallboard and likely directly influenced the decreased fungal growth observed on this material. The mold-resistant gypsum material also showed a significant increase in bacterial alpha diversity, and bacterial and viral particle abundance, as well as a decrease in metabolite diversity, likely a result of reduced fungal growth. Penicillium taxa were positively correlated with thiabendazole, which suggested the persistence of resistant strains. Also, specific to the wet samples, Bacillus abundance was positively correlated with the azoxystrobin, suggesting bi-directional competitive adaptation, and positively correlated with metabolites known to interfere with Pseudomonas biofilm formation, which could explain the anti-correlation between these taxa. As expected, high moisture conditions enabled faster growth of inoculating microorganisms, whose composition, chemistry, and competition was shaped by surface material, suggesting that both fungal and bacterial growth need to be considered when determining the impact of dampness in built environments.

microbiology↗

bioRxiv2018

Crowdsourced study of children with autism and their typically developing siblings identifies differences in taxonomic and predicted function for stool-associated microbes using exact sequence variant analysis.

BackgroundThe existence of a link between the gut microbiome and autism spectrum disorder (ASD) is well established in mice, but in human populations efforts to identify microbial biomarkers have been limited due to problems stratifying participants within the broad phenotype of ASD and a lack of appropriately matched controls. To overcome these limitations and investigate the relationship between ASD and the gut microbiome, we ran a crowdsourced study of families 2-7 year old sibling pairs, where one child of the pair had a diagnosis of ASD and the other child did not.\n\nMethodsParents of age-matched sibling pairs electronically consented and completed study procedures via a secure web portal (microbiome.stanford.edu). Parents collected stool samples from each child, responded to behavioral questionnaires about the ASD childs typical behavior, and whenever possible provided a home video of their ASD childs natural social behavior. We performed DNA extraction and 16S rRNA amplicon sequencing on 117 stool samples (60 ASD and 57 NT) that met all study design eligibility criteria. Using DADA2, Exact Sequence Variants (ESVs) were identified as taxonomic units, and three statistical tests were performed on ESV abundance counts: (1) permutation test to determine differences between sibling pairs, (2) differential abundance test using a zero-inflated gaussian mixture model to account for the sparse abundance matrix, and (3) differential abundance test after modeling under a negative binomial distribution. The potential functional gene abundance for each sample was also inferred from the 16S rRNA data, providing KEGG Ortholog (KO), which were analyzed for differential abundance.\n\nResultsIn total, 21 ESVs had significantly differentially proportions in stool of children with ASD and their neurotypical siblings. Of these 21 ESVs, 11 were enriched in neurotypical children and ten were enriched in children with ASD. ESVs enriched in the ASD cohort were predominantly associated with Ruminococcaceae and Bacteroidaceae; while those enriched in controls were more diverse including taxa associated with Bifidobacterium, Porphyromonas, Slackia, Desulfovibrio, Acinetobacter johnsonii, and Lachnospiraceae. Exact Variant Analysis suggested that Lachnospiraceae was specific to the control cohort, while Ruminococcaceae, Tissierellaceae and Bacteroidaceae were significantly enriched in children with ASD. Metabolic gene predictions determined that while both cohorts harbor the butyrogenic pathway, the ASD cohort was more likely to use the 4-aminobutanoate (4Ab) pathway, while the control cohort was more likely to use the pyruvate pathway. The 4Ab pathway releases harmful by-products like ammonia and can shunt glutamate, affecting its availability as an excitatory neurotransmitter. Finally, we observed differences in the carbohydrate uptake capabilities of various ESVs identified between the two cohorts.

microbiology↗