Biology subjects

Newton, D. P.

Publications and source records attributed to Newton, D. P..

4 recordsLinked to original sources

bioRxiv2024

The network structure of cross-feeding impacts microbial community diversity under growth-inhibiting stresses

Perturbations such as dietary shifts and drug treatment can reduce gut microbiome diversity, with negative health effects on the host, but predicting changes to community diversity is challenging due to the many mechanisms by which species interact. While both nutrient competition and cross-feeding can play major roles in microbiota assembly, the effect of environmental stresses such as antibiotics is typically studied experimentally in monoculture, and most theoretical studies have focused on communities that interact via nutrient competition alone. To investigate the interplay between nutrient competition, stresses that inhibit growth, and cross-feeding, we introduce a consumer-resource model that includes all three factors and captures a wide range of cross-feeding network architectures with a single parameter. For three-species communities, we found that coexistence during narrow-spectrum growth inhibition was maximal with a cyclic cross-feeding network, while fully connected cross-feeding networks maximized coexistence during broad-spectrum growth inhibition. However, the effects of cyclic cross-feeding were particularly sensitive to community size and the number of targeted species; for communities with more than six species and resources, cyclic cross-feeding can be detrimental to coexistence due to instability. Our findings highlight the complex effects of cross-feeding network architecture on coexistence when growth inhibition reshapes the nutrient competition landscape, with potential applications to microbial communities in all natural environments, where they are often exposed to agents such as drugs, temperature, and pH modulation.

ecology↗

bioRxiv2024

Nutrient competition predicts gut microbiome restructuring under drug perturbations

Human gut commensal bacteria are routinely exposed to various stresses, including therapeutic drugs, and collateral effects are difficult to predict. To systematically interrogate community-level effects of drug perturbations, we screened stool-derived in vitro communities with 707 clinically relevant small molecules. Across [~]5,000 community-drug interaction conditions, compositional and metabolomic responses were predictably impacted by nutrient competition, with certain species exhibiting improved growth due to adverse impacts on competitors. Changes to community composition were generally reversed by reseeding with the original community, although occasionally species promotion was long-lasting, due to higher-order interactions, even when the competitor was reseeded. Despite strong selection pressures, emergence of resistance within communities was infrequent. Finally, while qualitative species responses to drug perturbations were conserved across community contexts, nutrient competition quantitatively affected their abundances, consistent with predictions of consumer-resource models. Our study reveals that quantitative understanding of the interaction landscape, particularly nutrient competition, can be used to anticipate and potentially mitigate side effects of drug treatment on the gut microbiota.

microbiology↗

bioRxiv2022

Antibiotic effects on microbial communities are modulated by resource competition

Antibiotic treatment significantly impacts the human gut microbiota, but quantitative understanding of how antibiotics affect community diversity is lacking. Here, we build on classical ecological models of resource competition to investigate community responses to antibiotic-induced species-specific death rates. Our analyses highlight the complex dependence of species coexistence that can arise from the interplay of resource competition and antibiotic activity, independent of other biological mechanisms. We show that resource competition can cause richness to change non-monotonically as antibiotic concentrations are increased. We identified resource competition structures that cause richness to depend on the order of sequential application of antibiotics (non-transitivity), and the emergence of synergistic and antagonistic effects under simultaneous application of multiple antibiotics (non-additivity). These complex behaviors can be prevalent, especially when generalist consumers are targeted. Communities can be prone to either synergism or antagonism, but typically not both, and antagonism is more common. Furthermore, we identify a striking overlap in competition structures that lead to non-transitivity during antibiotic sequences and those that lead to non-additivity during antibiotic combination, suggesting that our analysis is broadly applicable across a wide range of clinically relevant antibiotic treatment schemes. In sum, our results will facilitate the engineering of community dynamics via deleterious agents.

ecology↗

bioRxiv2021

Construction and characterization of a genome-scale ordered mutant collection of Bacteroides thetaiotaomicron

Genomic analyses have revealed how the gut microbiota impacts human health. However, knowledge about the physiology of most gut commensals is largely lacking. Here, we sorted cells from a pooled library to construct an ordered collection of transposon-insertion mutants in the model commensal Bacteroides thetaiotaomicron. We applied a pooling strategy with barcode sequencing to locate mutants and created a condensed collection with single insertions in 2,565 genes. This effort enabled the development of an accurate model for progenitor-collection assembly, which identified strain-abundance biases and multi-insertion strains as important factors that limit coverage. To demonstrate the potential for phenotypic screening, we analyzed growth dynamics and morphology of the condensed collection and identified growth defects and altered cell shape in the sphingolipid-synthesis gene BT0870 and the thiamine scavenging gene BT2397. Analyses of this collection and utilization of the platform described herein to construct future ordered libraries will increase understanding of gut commensal physiology and colonization strategies.

microbiology↗