Biology subjects

Freire, T.

Publications and source records attributed to Freire, T..

3 recordsLinked to original sources

bioRxiv2026

Modeling the human vaginal microbiome and its protection against pathogens using the replicator framework for invasion

The human vaginal microbiota plays a central role in protecting against urogenital infections, including bacterial vaginosis, yeast infections, HIV, and urinary tract infections. However, the ecological mechanisms connecting microbial community structure to clinical indicators such as Nugent scores remain poorly understood. Although machine-learning approaches can accurately predict bacterial vaginosis (BV) from microbiota profiles, they provide limited biological insight. Here, we introduce a mechanistic framework that links vaginal microbiota composition to Nugent score and identifies key ecological interactions underlying health and disease-associated community states. We analyzed microbiota data from an already published North American women cohort, aggregating taxa at the phylum level to improve stability and interpretability. Using a replicator model, we quantified both the direct contributions of individual phyla and nonlinear effects arising from pairwise interactions, capturing transitions among healthy, intermediate, and BV-positive states. The model predicted BV-positive status with 92% accuracy for the 394 women in the study, on par with machine-learning benchmarks. More importantly, it provides a clear ecological interpretation of BV-associated community change. Beyond the BV setting, the model itself illustrates a general proof-of-concept for microbiota-invader links via the replicator formalism.

microbiology↗

bioRxiv2025

Differential effects of postpartum sleep restriction on maternal and offspring immunity in the rat

Backgroundsleep disturbances can trigger a wide range of physiological consequences, affecting hormonal regulation, metabolism, cognitive function, and immune responses. Human mothers worldwide frequently experience sleep restriction and fragmentation, a pattern also observed in other mammalian mothers, such as rats. These alterations may add to sleep disturbances unrelated to motherhood. Considering this, we wondered about the impact of sleep restriction in postpartum mother rats on their immunological status. Furthermore, given that early-life experiences can shape the immune system and that even subtle parental changes can influence offspring development, we hypothesized that maternal sleep loss might also exert detrimental effects on the pups. In this study, we investigated the effects of acute and chronic maternal sleep restriction during the postpartum period on immune parameters in both mother rats and their offspring by analyzing antibody titers and systemic inflammation. Methodsmother rats were surgically implanted with electrodes for polysomnographic recordings and for sleep deprivation (deep electrodes targeting the mesopontine wake-promoting area). From postpartum day 5 to day 9, lactating dams were randomly assigned to one of three groups: chronic sleep restriction (CSR; 6 h of sleep deprivation per day for five consecutive days), acute sleep restriction (ASR; 6 h of sleep deprivation only on postpartum day 9), or control (undisturbed). On postpartum day 9, mothers were milked, and blood samples from both mothers and pups were subsequently collected. ELISA assays quantified IL-17A, IL-6, IgG, and IgG2a in maternal serum; IgG and IgG2a in milk; and IgG in pup serum. Hematological parameters, including leukocyte profiles, were also assessed in peripheral blood of dams and pups. Resultsmaternal immune parameters analyzed remained unaffected by sleep restriction. IgG levels were lower in male pups from mothers subjected to ASR (5560 {+/-} 734 {micro}g/mL) compared with the control group (8666 {+/-} 463 {micro}g/mL; p = 0.025), whereas female pups showed no significant changes. Additionally, both female (4.10 {+/-} 0.58) and male (3.81 {+/-} 0.42) pups from dams subjected to CSR exhibited higher absolute lymphocytes counts relative to the control group (females: 2.28 {+/-} 0.25, p = 0.004; males: 2.44 {+/-} 0.25; p = 0.029). ConclusionsChronic and acute maternal sleep restriction had distinct impacts on offspring immunity, altering serum antibody and leukocyte profiles, while leaving maternal parameters unaffected. These results indicate that maternal sleep loss can influence the offspring even in the absence of detectable maternal immune alterations, with male pups being especially susceptible.

immunology↗

bioRxiv2024

Linking spatial drug heterogeneity to microbial growthdynamics in theory and experiment

Diffusion and migration play pivotal roles in microbial communities - shaping, for example, colonization in new environments and the maintenance of spatial structures of biodiversity. While previous research has extensively studied free diffusion, such as range expansion, there remains a gap in understanding the effects of biologically or physically deleterious confined environments. In this study, we examine the interplay between migration and spatial drug heterogeneity within an experimental meta-community of E. faecalis, a Gram-positive opportunistic pathogen. When the community is confined to spatially-extended habitats ( islands) bordered by deleterious conditions, we find that the population level response depends on the trade-off between the growth rate within the island and the rate of transfer into regions with harsher conditions, a phenomenon we explore by modulating antibiotic concentration within the island. In heterogeneous islands, composed of spatially patterned patches that support varying levels of growth, the populations fate depends critically on the specific spatial arrangement of these patches - the same spatially averaged growth rate leads to diverging responses. These results are qualitatively captured by simple simulations, and analytical expressions which we derive using first-order perturbation approximations to reaction-diffusion models with explicit spatial dependence. Among all possible spatial arrangements, our theoretical and experimental findings reveal that the arrangement with the highest growth rates at the center most effectively mitigates population decline, while the arrangement with the lowest growth rates at the center is the least effective. Extending this approach to more complex experimental communities with varied spatial structures, such as a ring-structured community, further validates the impact of spatial drug arrangement. Our findings suggest new approaches to interpreting diverging clinical outcomes when applying identical drug doses and inform the possible optimization of spatially-explicit dosing strategies. Author summaryIn this study, we develop an automated platform to experimentally investigate short-term population growth and migration dynamics under spatial drug heterogeneity. Our findings reveal that the collective spatial response of the population can vary significantly, even with the same migration rate and averaged drug dose, due to different spatial drug arrangements. By constructing a simple reaction-diffusion model, we observed that simulated short-term spatial growth rate closely matches the experimental data. Furthermore, this short-term spatial growth rate aligns well with the long-term spatial growth rate, defined by the largest eigenvalue, as the spatial system quickly enters the equilibrium growth state. Using concepts from perturbation theory, we derived an analytical relationship between the boundary diffusion effect, homogeneous growth effect, and heterogeneous effect. Our results highlight that in spatially-extended habitats, the spatial growth response is an emergent property. The bacterial population quickly enters equilibrium growth, suggesting that the spatial growth rate measured at an ecological scale may be used to predict resistance evolutionary behavior.

biophysics↗