Biology subjects

Schreiber, S.

Publications and source records attributed to Schreiber, S..

At least 19 recordsLinked to original sources

bioRxiv2026

Extinction order affects community composition under strong competition and asymmetric species interactions

Extinction is a fundamental process impacting how community compositions change though time. Despite this, relatively few studies have examined how the order of species loss in multispecies extinction sequences can differentially impact the composition of the resulting disassembled community, known as an inverse priority effect. Here, we investigate the prevalence and predictors of inverse priority effects across a range of ecological contexts. First, we extend previous theory by deriving all possible cases of inverse priority effects in three-species Lotka-Volterra systems of coexisting competitors with equal intrinsic growth rates. We show that communities with strong, asymmetric competitive interactions are more likely to exhibit inverse priority effects. We then use a random matrix approach to demonstrate that inverse priority effects become more prevalent in more speciose communities and vary with the length of the extinction sequence. Furthermore, in speciose communities, inverse priority effects become increasingly likely with less facilitative or more competitive average interspecific interactions. Together, our results suggest that inverse priority effects are likely common in species-rich communities, particularly those with strong competition and asymmetric species interactions, warranting further theoretical and empirical investigation.

ecology↗

bioRxiv2026

Reply to: Structural polymorphism of amyloid fibrils in ATTR amyloidosis revealed by cryo-electron microscopy

In the paper by Nguyen et al, published in Nature Communications in 2024, we describe structural polymorphism in fibrils extracted from patients with ATTR amyloidosis. ATTR amyloidosis is characterized by deposition of transthyretin amyloid fibrils across multiple organs, resulting in marked phenotypic variability. Previous studies on ATTR suggest its phenotypic variability may be linked to differences in fibril structure, as demonstrated in amyloid diseases such as AA amyloidosis, tauopathies, or synucleinopathies. Thus far, most ATTR fibrils adopt a strikingly similar fold across patients and affected organs. The most notable exception is described in the study by Nguyen et al., where we report the identification of two co-existing polymorphs in cardiac fibrils from three patients with the ATTRv-I84S variant. These cardiac polymorphs differ in conformation of the segment Gly57 to Gly67, termed the gate, which regulates access to a central polar channel within the fibril core. In one polymorph, the gate adopts an open conformation, exposing the channel, whereas in the other it is closed, shielding it. Whether these polymorphs extend beyond cardiac tissue remains unknown. Here, we address this question by extending our analysis to additional organs from a fourth patient with ATTRv-I84S amyloidosis.

biophysics↗

bioRxiv2026

A pro-inflammatory effector-memory T cell program links peripheral EBV priming to CNS autoimmunity

T and B cell-mediated immunosurveillance of the central nervous system (CNS) can become maladaptive in multiple sclerosis (MS). Epstein-Barr virus (EBV) is a likely driver of MS, yet how exactly EBV-specific T cells contribute remains unclear. We generated an antigen-resolved atlas of blood and cerebrospinal fluid (CSF) T cells from untreated MS patients and controls. T cell clones carrying a GZMK effector-memory program in blood were CSF-biased, particularly in MS, and associated with EBV reactivity. In CSF, EBV-reactive GZMK CD8 T cells engaged B lineage cells. Activated CD8 T cells promoted atypical B cell and plasmablast formation, whereas GZMK-enriched effector-memory cells induced IL-6 and IL-8 release from myeloid cells. Together, these findings identify an infection-imprinted, CNS-biased state and support a model in which EBV-specific CD8 T cells contribute to inflammation through a non-canonical mode of B cell and myeloid cell activation.

immunology↗

bioRxiv2026

Mesoscale medial temporal lobe connectivity patterns relate to tau pathology and memory in older adults

The medial temporal lobe (MTL) is crucial for episodic memory. Tau pathology is a hallmark of Alzheimer's disease (AD) and accumulates in layer-specific patterns in the MTL during aging. It is, however, unclear whether early AD pathology relates to mesoscale network signatures distinct from non-pathological aging. To address this gap, we acquired 7 Tesla submillimeter-resolution resting-state fMRI, plasma-based AD biomarkers, glial fibrillary acidic protein (GFAP) levels, APOE genotype, regional [18F]PI-2620 tau PET burden, and longitudinal episodic memory data in 75 cognitively unimpaired older adults. Older age was associated with lower perirhinal-hippocampal connectivity and lower network segregation, whereas higher plasma-based AD pathology was associated with higher perirhinal-hippocampal connectivity. Furthermore, temporal-lobe tau burden was related to altered connectivity patterns in tau-vulnerable MTL subfields and layers, dependent on GFAP levels. Retrosplenial tau burden was associated with higher hippocampal-retrosplenial connectivity consistent with tau spread along canonical hippocampal output pathways. Finally, higher connectivity within the hippocampus attenuated the negative association between temporal-lobe tau burden and memory performance but predicted unfavorable memory trajectories. Our findings show differential associations of age and AD pathology with mesoscale MTL-connectivity patterns. Importantly, increased hippocampal connectivity may support memory function in the short term while contributing to subsequent memory decline.

neuroscience↗

bioRxiv2026

From Lab Notes to Linked Data: MeSyTo for Ontology-Driven Metadata in Toxicological Omics

Toxicological omics studies require comprehensive metadata to support reproducibility, interoperability, and regulatory reuse. However, metadata requirements differ across public repositories, reporting frameworks, and laboratory workflows, resulting in inconsistent annotation and limited data integration. To address this challenge, we developed MeSyTo (Metadata for Systems Toxicology), an ontology-driven framework for harmonizing metadata across toxicological omics. Metadata concepts from public repositories, the OECD Omics Reporting Framework (OORF), community standards, and institutional workflows were semantically aligned and implemented as the MeSyTo Metadata Model (MMM). The MMM serves as the basis for the automatic generation of SHACL validation shapes and framework-specific metadata profiles, while curated value sets are represented as SKOS controlled vocabularies to support metadata collection and validation. The current implementation comprises 105 ontology classes and 527 data properties and supports transcriptomics, proteomics, and metabolomics. A prototype web application demonstrates ontology-driven metadata collection with integrated semantic validation and ontology-based term resolution. The ontology, validation shapes, controlled vocabularies, generation scripts, and software are publicly available as open-source resources. MeSyTo provides a reusable semantic foundation for harmonized, machine-actionable metadata and facilitates repository submission, regulatory reporting, and interoperable data exchange across toxicological omics studies.

bioinformatics↗

bioRxiv2026

Automated quantification of white matter hyperintensity confluence: A measure of spatial organisation beyond volume and visual rating scales

White matter hyperintensities (WMH) are a highly prevalent finding on FLAIR MRI scans and a prominent feature of white matter pathology across cerebrovascular and neurodegenerative diseases. Currently, WMH are assessed with visual rating scales such as the Fazekas scale or with their volume, as calculated from automatic or manual segmentations. Both methods have limitations: Visual rating scales are rater-dependent and coarse, while WMH volume does not take the confluence of lesions into account and thus disregards their spatial organisation. As an alternative, here we propose a novel automated method for quantifying the confluence of white matter hyperintensities on a continuous standardised scale between 0 and 1. The metric is based on WMH segmentations from routine MRI and quantifies the extent to which individual WMH merge into coherent lesions, independently of total lesion volume. We apply the method to QMIN-MC, a large UK memory clinic cohort, and show associations of the confluence metric with age, cognitive performance across domains, and Fazekas ratings. Participants with vascular and mixed dementia showed higher confluence than other diagnostic groups, whereas cognitively unimpaired participants showed lower confluence. However, confluence did not explain additional cognitive variance after accounting for log-transformed WMH volume. Findings were validated in DELCODE, an independent cohort of individuals with neurodegenerative disorders, replicating our original results. In this validation cohort, periventricular WMH confluence remained associated with cognition after adjustment for WMH volume. These findings introduce WMH confluence as a reproducible, automated, and fine-grained measure of lesion spatial organisation. It provides complementary information about morphological WMH severity beyond volume and is an alternative to visual rating scales. Although related to WMH volume in memory-clinic populations, confluence captures clinically interpretable information and may complement existing WMH measures for improved lesion characterisation in studies of white matter disease, ageing, and cognitive impairment.

neuroscience↗

bioRxiv2026

From Lotka-Volterra Dynamics to Community Assembly: Theory, Topography, and Empirical Applications

AO_SCPLOWBSTRACTC_SCPLOWO_LICommunity assembly graphs (CAGs) summarize which species combinations can coexist and how single-species invasions drive transitions between them, encoding the pathways, alternative endpoints, and cycles that make up a communitys assembly history. Constructing CAGs from dynamical models requires methods that are both computationally tractable and faithful to the underlying ecological dynamics. However, existing methods rely on restrictive assumptions, such as global stability, that exclude alternative stable states and non-equilibrium dynamics known to occur in empirical systems. C_LIO_LIWe develop a computational pipeline that constructs CAGs from any generalized Lotka-Volterra model. Building on the invasion graph framework and its connection to permanence, the pipeline verifies that community dynamics are bounded, identifies which subsets of species coexist in the sense of permanence, determines which single-species invasions are dynamically realized, and assigns each community a topographic height equal to the length of the longest assembly path leading to it. We also provide a numerical algorithm to simulate the dynamics of community assembly. C_LIO_LIWe prove several general properties of the resulting graphs, including that a successful invader is never subsequently excluded and that, in the absence of assembly cycles, permanent communities can be reassembled by introducing their species one at a time in the right order. We prove that the CAG faithfully reproduces the compositional shifts seen in the numerically simulated dynamics of assembly. Applying the pipeline to three empirically based models (a New Zealand grassland, a European pasture, and a Puerto Rican ant community), we show how competition strength and mutualistic feedbacks reshape the assembly landscape and how intransitive competition generates assembly cycles. C_LIO_LIOur approach accommodates alternative stable states and non-equilibrium dynamics without requiring global stability, and it turns the long-standing landscape metaphor into a quantitative, mechanistically grounded object by resolving what "height" means. More broadly, it makes the topography of the assembly pathways measurable, providing a way to compare the historical contingency and predictability of the assembly in ecological systems. C_LI

ecology↗

bioRxiv2026

The in-vivo microstructural profile of human hippocampal subfield CA1 and its relation to memory performance

The hippocampal CA1 subregion supports learning, memory formation, and spatial navigation. Although its three-layered architecture has been described in ex-vivo investigations, the in-vivo microstructural profile of CA1 and its relation to individual variations in memory performance remain poorly characterized. In this study, we used ultra-high field structural MRI at 7 Tesla to investigate the depth-dependent myelination patterns (measured by quantitative T1) of CA1 in younger adults, their relation to the local arterial architecture, and their association with individual differences in cognitive functions, specifically memory performance. Results show that left and right CA1 present depth-dependent patterns of myelination, with the outer and inner compartments showing higher myelination than the middle compartment. No significant relationship between layer-specific myelination of CA1 and distance to the nearest artery was observed. Right CA1 was found to be more myelinated than left CA1. Pairwise correlations and regression models showed that higher left CA1 myelination is linked to higher accuracy in object localization. Together, our data demonstrates the feasibility of describing the three layered myelin architecture of CA1 in vivo, and provides information on how alterations in the architecture of CA1 may relate to alterations in cognitive performance in younger adults.

neuroscience↗

bioRxiv2026

STING safeguards epithelial genome integrity and protects from carcinogenesis via mitotic checkpoint control

STING is canonically known for mediating interferon responses to cytosolic DNA, yet its cell-intrinsic role in genome maintenance beyond the immune context is unknown. Here we show that epithelial STING functions as a type I interferon-independent genome-integrity checkpoint. STING loss impairs homologous recombination repair, attenuates ATM-associated damage signaling, elevates CDK1 activity, and causes chromosomal instability revealed by single-cell Strand-seq, culminating in spontaneous intestinal adenocarcinoma. These defects arise before tumor formation and confer selective vulnerability to CDK inhibition in tumor organoids and human colorectal cancer cells. Our findings identify STING as a cell-autonomous guardian of epithelial genome stability that restrains chromosomal instability-driven tumor evolution beyond its canonical immune function.

cancer biology↗

bioRxiv2025

Systematic screening of tryptophan metabolism identifies site- and microbial-specific signatures of tryptophan utilization in experimental colitis

BackgroundAltered tryptophan (Trp) metabolism and disrupted nicotinamide adenine dinucleotide (NAD) synthesis are hallmarks of IBD, yet how intestinal microbiota contribute to these metabolic shifts during intestinal inflammation remains poorly understood. MethodsWe used targeted metabolomics to systematically profile Trp- and NAD-related metabolites across multiple biological compartments - including tissues, luminal contents, stool, and serum - in mice treated with dextran sulfate sodium (DSS) alone or in combination with a broad-spectrum antibiotic (ABX) cocktail. ResultsMicrobial depletion significantly attenuated colitis and increased host Trp bioavailability, implicating the gut microbiota as a competitive Trp consumer. In DSS colitis, Trp degradation along the kynurenine pathway (KP) was exaggerated but blocked at the key KP enzyme quinolinate phosphoribosyltransferase (QPRT), resulting in mucosal NAD(H) depletion. ABX co-treatment normalized metabolite conversion along the KP and restored mucosal NAD(H) levels, revealing a dual role of the gut microbiota during colitis: while they compete with the host for Trp utilization, they simultaneously shape host KP regulation and NAD de novo synthesis, supporting host energy homeostasis. ConclusionOur findings demonstrate that mucosal NAD de novo synthesis is a microbially regulated metabolic process that alleviates intestinal inflammation and may represent a novel therapeutic target in IBD through modulation of the gut microbiota or their metabolites.

immunology↗

bioRxiv2025

The dynamic role of HLA proteins on compositional alterations of T-cell repertoires in inflammatory bowel disease

BackgroundInflammatory bowel disease (IBD), which is characterised by genetic predispositions and dysregulated immune responses, is rapidly emerging as a global health challenge. Genetic variations in the human leukocyte antigen (HLA) region are strongly associated with IBD; nonetheless, the functional consequences of this variation on the composition of T-cell receptors remain poorly understood. MethodsWe conducted comprehensive CDR3-QTL mapping using T-cell receptor beta (TRB) repertoires paired with HLA allotypes from 1,973 individuals, including 1,201 individuals with IBD and 772 healthy controls (HCs), to explore the role of the HLA allelic variants on TRB composition. Using network analyses, we defined key CDR3 motifs of public clones that were linked to risk HLA alleles for chronic inflammatory diseases. ResultsWe identified novel sites within both HLA class I and class II proteins that were strongly linked to TRB amino acid composition - cdr3QTLs, in both HCs and individuals with IBD. Those sites in HLA-DRB1 and HLA-DQ had stronger effects on CDR3 composition than did the disease in the IBD cohort. In HCs, but not in UC or CD, the strongest HLA signals that affected expanded clones, overlapped with primary CD risk loci from GWAS, e.g., DRB1 site 70 and DQA1 site 25. The strongest CD-specific effects on TRB composition were found in HLA-B, especially at sites that modulate viral responses (e.g., HLA-B sites 9, 67). Finally, the main risk HLA alleles for chronic inflammatory diseases clustered together based on the physicochemical properties of residues mapped to cdr3QTLs, suggesting that risk alleles might exert similar effects on the TRB repertoire. ConclusionStructurally, the main cdr3QTLs in both HLA class I/II are located in peptide-binding sites or sites contacting TCRs, highlighting their direct and antigen-mediated influences on TRB repertoires. Our findings suggest that cdr3QTLs in HLA class I exert IBD-specific effects on the TRB composition, influencing the dysregulated T cell responses implicated in IBD pathogenesis, possibly on the earlier stages of T cell development. While HLA class II cdr3QTLs show universal effects and strong associations with T-cell receptors, irrespective of disease.

immunology↗

bioRxiv2025

Long-Term Intestinal Epithelial Remodeling Induced by Acute Protein-Energy Malnutrition

Protein-energy malnutrition (PEM) is a global health burden with lasting effects that extend well beyond the initial nutrient deficiency. To systematically investigate the long-term effects of a single episode of PEM on the structure and function of the intestinal epithelium and its associated microbiota, we employed a comprehensive multi-omics approach, including (spatial) transcriptomics, DNA methylation analysis, fecal metagenomics, and metabolomics. Our findings show that PEM persistently alters the intestinal epithelium by depleting Paneth cells and suppressing antimicrobial gene expression - changes linked to DNA methylation that persist despite dietary recovery. In germ-free mice, the sustained epithelial phenotype after was absent. We identified the microbial lipid metabolite 9-HODE and epigenetically deregulated PPAR-driven GDF15 expression as key molecular drivers of the persistent PEM-induced Paneth cell dysfunction. Targeting microbial lipid production and its link to the host GDF15 pathway could offer novel therapeutic strategies for long-term consequences of malnutrition and other Paneth cell-associated diseases.

immunology↗

bioRxiv2025

Implantable Living Materials Autonomously Deliver Therapeutics from Contained Engineered Bacteria

Microbes are increasingly utilized as living therapeutic vehicles, yet their uncontrolled dissemination in the body has long remained a roadblock to clinical development. Physical containment, while widely used for mammalian cells, remains largely unattainable due to eventual bacteria escape. Here, we present an implantable material platform that encapsulates and confines bacteria, wherein synthetically engineered microbes produce therapeutic payloads from within. To prevent microbial escape, we developed a hydrogel scaffold with dual mechanical features: high stiffness to regulate bacterial proliferation and high toughness to resist material fracture under physiological stress. This design achieved complete bacterial containment for over six months and withstood multiple forms of mechanical loading that otherwise caused catastrophic material failure. By genetically engineering embedded bacteria, we endowed the material with environmental sensing and on-demand therapeutic release capabilities and demonstrated autonomous treatment in a murine prosthetic joint infection model. This multimodal strategy provides a safe and generalizable framework for deploying microbial medicines in vivo and supports their use as autonomous drug depots across a range of disease settings.

bioengineering↗

bioRxiv2025

CD36 is a metabolic checkpoint for Th2 cell tissue residency during allergic airway inflammation

The prevalence of allergic diseases, including asthma, continues to rise in industrialized societies, yet the mechanisms sustaining pathogenic T helper 2 (Th2) responses remain incompletely understood. Here, we show that patients with allergic asthma exhibit elevated lipophilic volatile organic compounds in exhaled air and altered fatty acid-metabolism gene expression in sputum-derived Th2 cells. Using a mouse model of house dust mite-induced allergic airway inflammation, we find that the lipid transporter CD36 is dispensable for T follicular helper and germinal center B cell responses but is critical for maintaining lung-resident memory Th2 cells. CD36 regulates GATA3 and PPAR{gamma} expression in lung-resident memory Th2 cells and their interaction with type-2 conventional dendritic cells during airway inflammation. In human T cells, pharmacological inhibition of CD36 does not impair initial activation but blocks terminal Th2 differentiation. These findings identify CD36 as a metabolic checkpoint that sustains Th2 effector function and tissue residency, and establish lipid metabolism as a yet unrecognized therapeutic target in allergic asthma. SummaryAllergic asthma is marked by rising prevalence yet the drivers of persistent T helper 2 (Th2) immunity remain unclear. We show that asthma patients exhibit altered fatty acid-metabolism signatures in sputum Th2 cells and elevated lipophilic volatile organic compounds in exhaled air. In a mouse model of house dust mite-induced airway inflammation, the lipid transporter CD36 was dispensable for germinal center responses but essential for lung-resident memory Th2 cells, controlling GATA3 and PPAR{gamma} expression and promoting cDC2 interactions. Pharmacological inhibition of CD36 in human T cells preserved activation but blocked terminal Th2 differentiation. These findings identify CD36 as a metabolic checkpoint that sustains Th2 effector function and tissue residency, and nominate it as a therapeutic target in allergic asthma. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=117 SRC="FIGDIR/small/676489v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@117da6eorg.highwire.dtl.DTLVardef@105934corg.highwire.dtl.DTLVardef@109903corg.highwire.dtl.DTLVardef@dc9345_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2025

Robustness through variability: ion channel isoform diversity safeguards neuronal excitability

Neural circuits are composed of different neuron types that exhibit distinctly different computational properties resulting from the sets of ion channels expressed. Profound insight exists into how neural computations arise from the precise regulation of ion channels (Armstrong et al., 1998; Lai, Jan, 2006; Nusser et al., 2012), how degenerate channel properties support similar computations (Marder, Prinz, 2002; Marder, Goaillard, 2006), and how channelopathies affect brain function (Kullmann, 2010). However, it remains elusive why neurons express many more channels, and isoforms thereof, than required to tune their specific excitabilities. Here, we employ an experiment-theory approach pairing electrophysiology with Drosophila genetics, and mathematical modelling to show that the variance in membrane properties that results from ion channel diversity promotes the robustness of neuron-type specific functions. Specifically, we show that the robustness of flight motoneuron coding properties to internal and external perturbations is significantly enhanced by the diversity of calcium channel splice isoforms expressed. Importantly, increased excitability robustness to perturbations of outward currents or temperature does not require adjustments in calcium channel mean properties. Instead, increases of the variance of calcium channel gating properties that result from channel isoform diversity broaden the dynamic input range the neuron can compute without reaching depolarization block. This broadens our concept of the functional consequences of the tremendous variety and diversity of ion channels expressed in brains. One Sentence SummaryThe variance of calcium channel gating properties is increased by channel isoform diversity and aids neuronal coding and excitability robustness.

neuroscience↗

bioRxiv2025

Integrate-and-fire neurons with potassium dynamics that capture switches in neuronal excitability class and firing regime

In conductance-based models, spiking-induced ion concentration fluctuations can alter the excitability of single neurons. In particular, in class I models, variations in potassium concentration can induce qualitative changes in the dynamics through a codimension-2 bifurcation known as the saddle-node-loop (SNL). Investigating the implications of such effects at the level of neuronal networks will require computationally efficient single neuron models that still capture ion concentration dynamics realistically. To this end, we propose a method to derive a phenomenological model capturing the coupled extracellular potassium and voltage dynamics of a given class I conductance-based model. Rather than fitting voltage traces, we calibrate a canonical reduced model to the two-parameter bifurcation structure of the target model, with input current and a physiological parameter as coordinates. This preserves the location and type of dynamical transitions as the physiological parameter varies, allowing a single reduced model to capture neuronal dynamics across qualitatively different regimes. The resulting model is an extension of the quadratic integrate-and-fire model, in which extracellular potassium accumulation alters voltage dynamics by increasing the reset voltage. We apply our systematic reduction procedure to the Wang-Buzsaki model. Its phenomenological version exhibits quantitatively comparable dynamics and replicates the reshaping of the phase-response curve associated with the transition from SNIC to HOM spikes at elevated potassium. To illustrate the derived model's applicability, we perform a preliminary investigation of how changes in potassium concentration influence synchronization in networks.

neuroscience↗

bioRxiv2025

Multi-centered T cell repertoire profiling identifies novel alterations in the immune repertoire of individuals with inflammatory bowel disease and validates previous findings

IntroductionIBD is an incurable immune-mediated inflammatory disease (IMID), affecting the gut with a high rate of primary- and secondary-loss-of-response to therapy. By investigating the T cell receptor repertoire of individuals with IBD, novel therapeutic and preventive strategies can be identified, and a better understanding of IBD can be obtained. MethodsWhereas most studies have so far focused on the more diverse T cell receptor beta (TRB) repertoire, we here profiled the alpha (TRA) repertoire of three cohorts containing treatment-naive and treated individuals in addition to individuals living with the disease for >20 years, resulting in an exhaustive dataset containing the TRA repertoire of 2,151 individuals. ResultsUsing the generated datasets, we were able to replicate previous findings describing the expansion of Crohns-associated invariant T (CAIT) cells in individuals with Crohns disease (CD) in the three cohorts. Using a hypothesis-free statistical testing framework, we identified clonotypes that were associated with the disease at its different stages, e.g., at the time of diagnosis and decades post-diagnosis. By conducting a meta-analysis across the three cohorts, we were able to identify a set of clonotypes that were associated with the disease regardless of its stage. We validated our findings in a previously published independent test dataset from a German cohort, showing the robustness of the identified sets of clonotypes. ConclusionThe identified clonotypes are potential novel therapeutic targets to treat IBD, e.g., through targeted depletion. These clonotypes are also of major interest as they can be investigated in a targeted fashion to identify culprit antigen(s) in IBD.

immunology↗

bioRxiv2025

Bounded environmental stochasticity generates secondary Allee thresholds

A population exhibits an Allee effect when there is a critical density below which it goes extinct and above which it persists. Classical models with environmental stochasticity predict inevitable extinction, stemming from the assumption that environmental variation is normally distributed with rare but arbitrary large effect sizes. However, environmental fluctuations are bounded and often not normally distributed. To address this reality, I analyze piecewise deterministic Markov models (PDMPs) of populations experiencing Allee effects, where environmental dynamics are governed by a finite-state Markov chain. These models predict that populations can persist through the emergence of two threshold densities. Below the lower threshold, populations deterministically go extinct; above the higher threshold, they deterministically persist. At intermediate densities, populations experience stochastic bistability: with positive, complementary probabilities, they either go extinct or persist. Persistence becomes impossible when the carrying capacity in one environment falls below the Allee threshold in another. Such mismatch occurs only when the environmental state affects percapita growth rates non-monotonically, as when environments supporting higher carrying capacities also produce higher predation levels or greater mate limitation. This work demonstrates that incorporating realistic bounded environmental fluctuations substantially alters predictions about population persistence, with important implications for conservation and management.

ecology↗