Biology subjects

Tran, V.

Publications and source records attributed to Tran, V..

At least 19 recordsLinked to original sources

bioRxiv2026

Browning Lipid Nanoparticles Deliver Metabolic Benefits via Transient Conversion of White Adipose Tissue

Therapeutic strategies based on increasing uncoupled respiration (browning) in white adipose tissue (WAT) have great potential for treating obesity-related disorders such as diabetes and steatotic liver disease, but have not had a clinical impact because safe and efficient methods for browning WAT have not been developed. Lipid nanoparticles (LNPs) offer a promising platform for adipose-directed siRNA delivery; however, conventional formulations often exhibit limited activity in adipocytes and can induce inflammatory responses that may restrict repeated administration. Here we demonstrate that LNPs that contain ionizable lipids with three lipid tails and siRNAs targeting TLE3 and ZFP423 can efficiently transfect mature adipocytes and induce browning of WAT in vitro and in vivo while providing the biocompatibility needed for repeated subcutaneous injections. Repeated local administration of BLNPs in diet-induced obese mice resulted in sustained target gene silencing, increased expression of thermogenic markers, altered energy metabolism, and decreased hepatic lipid accumulation despite minimal effects on body weight relative to scramble siRNA controls. Collectively, these findings establish BLNPs as a promising platform for adipose-directed RNA delivery and targeted modulation of thermogenic pathways, providing a strategy for investigating how localized adipose tissue remodeling influences metabolic physiology.

bioengineering↗

bioRxiv2026

A meiotic B-type cyclin selectively drives mitotic progression and fidelity in cancer cells

Cell cycle transitions are driven by cyclins in complex with cyclin-dependent kinases (CDK). Here, we demonstrate that cyclin B3, an evolutionarily divergent B-type cyclin previously thought to function exclusively in female meiosis, is expressed in mitotic cells and interacts with both CDK1 and CDK2. We show that cyclin B3-CDK1/2 is essential for timely mitotic progression by ensuring proper chromosome alignment and stable kinetochore-microtubule interactions, while its overexpression accelerates mitosis and improves chromosome alignment kinetics. Through phospho-mass spectrometry, we identify several kinetochore and mitotic spindle components as substrates of cyclin B3-CDK1/2 in mitosis. Notably, cyclin B3 depletion disrupts mitotic progression in most cancer cell lines tested - including colorectal, osteosarcoma, and breast cancer models - while non-transformed cells are largely unaffected. These findings identify cyclin B3-CDK1/2 as a novel driver of mitotic progression and reveal a preferential dependency in a subset of cancer cells that may represent a potential therapeutic vulnerability.

cancer biology↗

bioRxiv2026

Lactococcus lactis subsp. cremoris Reprograms the Gut-Liver Axis and Protects Against Liver Injury

Metabolic diseases are increasingly linked to dysregulation of the gut-liver axis, highlighting the therapeutic potential of probiotics. Lactococcus lactis subsp. cremoris (LLC) protects against experimental hepatic steatosis, but the mechanisms underlying its benefits remain poorly understood. Here, we integrated untargeted metabolomics, gnotobiotic mouse models, targeted bile acid profiling, and liver injury paradigms to systematically define LLC-mediated metabolic reprogramming. LLC extensively remodeled serum and hepatic metabolomes in Western diet-fed mice, enriching pathways associated with lipid metabolism, xenobiotic biotransformation, and redox homeostasis. LLC attenuated ethanol-induced steatosis and acetaminophen-induced liver injury, accompanied by activation of Nrf2-dependent antioxidant programs and FXR signaling. LLC monocolonization was sufficient to reprogram the hepatic metabolome, revealing direct host metabolic effects. Reduced intestinal bile acid conjugation emerged as a prominent LLC-associated phenotype. Together, these findings identify LLC as a probiotic that reprograms the gut-liver metabolic axis to enhance metabolic resilience and hepatoprotection.

microbiology↗

bioRxiv2026

The Environmental, Endocrine, and Epigenetic Basis of Size Plasticity in a Superorganism

From plants to animals, genomes are responsive to environmental variation, the interaction of which can influence developmental processes and facilitate profound consequences on life-history and evolution. The interplay between genes and the environment is known to be mediated by the action of endocrine and epigenetic mechanisms including histone modifications. Ant development is plastic: environmental changes can induce diverse phenotypes, generating different castes that distinguish individuals by size, behaviour, and reproduction. While recent work has demonstrated that hormonal and epigenetic mechanisms underlie caste-specific trait variation in ants, the interplay of these mechanisms, and the process by which they mediate environmental changes to produce distinct trait variation, remains enigmatic. Here, we use the invasive fire ant Solenopsis invicta, dubbed a superorganism and known for its extreme worker caste size variation, to investigate the interplay between endocrine and epigenetic mechanisms in response to environmental variation. We found that sizing and developmental timing are both thermally and nutritionally plastic, influenced by juvenile hormone, ecdysone, histone (de)acetylation, and histone (de)methylation, and that these mediators interact and are thermally and nutritionally plastic. Surprisingly, fire ants break the Temperature-Size Rule, ecdysone makes ants bigger faster, and histone methylation disruption unexpectedly makes ants smaller. These and other findings suggest that an endocrine-epigenetic axis mediates thermal and nutritional plasticity underlying the extreme size variation that has evolved in the complex worker caste system in fire ants. More generally, we propose that an environment-endocrine-epigenetic (E3) approach will provide an integrative perspective on the development and evolution of adaptive phenotypes.

developmental biology↗

bioRxiv2025

Bioenergetic responses to β-adrenergic stimulation in beige adipocyte depend on actomyosin driven forces

Beige (BeAT) and white adipoctyes (WAT) reside within the same fat depots but differ in their responses to {beta}-adrenergic stimulation. While both activate classical PKA-mediated pathways, only beige adipocytes show induction of UCP1 expression and enhanced mitochondrial respiration, suggesting additional mechanisms that distinguish their responses. Here we uncover a parallel, non-canonical biomechanical pathway specific to beige adipocytes that is essential for thermogenic activation. Mechanistically, {beta}-AR stimulation induces a rapid Myh9-mediated actomyosin contraction and stiffening in beige, but not white, adipocytes that activates focal adhesion kinase (FAK), which we show to be critical for the expression of oxidative and thermogenic genes including UCP1 and PLIN5. These findings reveal a new biomechanical Myh9-FAK signaling arm downstream of b-adrenergic activation that differentiates thermogenic from white adipocytes.

cell biology↗

bioRxiv2025

Marginal zone B cells are antigenically activated, infiltrate the kidneys, and exacerbate angiotensin II-dependent hypertension in mice

AimsB cells contribute to the development of hypertension, yet, the specific B cell subsets involved, the mechanism underlying their activation, and the relevance of these responses to human disease remain poorly defined. Methods and resultsWe used single-cell RNA sequencing, single-cell B cell receptor (BCR) VDJ sequencing, and high dimensional flow cytometry to characterise B cell responses in murine angiotensin II-induced hypertension. Chronic angiotensin II infusion in male and female mice increased systolic blood pressure and selectively expanded marginal zone B (MZB) cells, with evidence of antigen-dependent activation, including clonal BCR expansion, enrichment of IGHV1 B cell receptor variants, and increased expression of activation markers (CD69 and Nur77). Intercellular communication analyses revealed enhanced antigen-presentation signalling between MZB and CD8+ T cells in hypertensive mice. Activated MZB-like memory B cells also accumulated in the kidneys of hypertensive mice. Consistent with these findings, multiomic analysis of kidneys from patients with hypertensive chronic kidney disease (CKD) demonstrated an increase in memory B cells with a MZB phenotype and enrichment of antigen-presentation-linked communication with CD8+ T cells. Importantly, hypertensive responses to angiotensin II infusion were significantly blunted in mice lacking MZB cells (BAFF-R-/-). ConclusionOur findings identify MZB cells as a selectively activated, antigen-responsive B cell subset that amplified pathogenic immune responses in murine and human hypertension. By linking subset-specific BCR activation to immune cross-talk and disease causality, this study identifies MZB cells - and the (auto)antigens that activate them - as promising targets for precision immunomodulatory strategies in hypertension.

physiology↗

bioRxiv2025

Molecular Dynamic Studies on the Interaction of a TatA Oligomer with Tat Translocon Substrates

The Tat Translocon directly utilizes the Proton Motive Force to transport folded proteins from the n-side to the p-side of energized membranes, targeting the thylakoid lumen of chloroplasts and the periplasmic space of Bacteria and Archaea. In most organisms the Translocon consists of three subunits, TatA, TatB and TatC exhibiting a stoichiometry of [~]20-50/1/1. While TatB/TatC recognize the canonical twin-arginine motif-containing signal sequence of substrate proteins, TatA has been hypothesized to interact with TatB/TatC and translocon substrates facilitating their transport across the membrane. TatA from E.coli contains a short transmembrane helix near the N-terminus, a longer amphipathic helix and a relatively large unstructured C-terminal domain. While the transmembrane and amphipathic helixes are required for Translocon activity, the C-terminal domain is, in large measure, dispensable. TatA has been hypothesized to form higher-order oligomers in the biological membranes. In this communication we have used 1000 ns-long course-grained molecular dynamic simulations to examine the interactions between a membrane-associated E. coli TatA nonamer, alone, and in association with two Tat Translocon substrate proteins, either OEE17 or TorA. In all simulations, either in the presence or absence of substrate, the TatA nonamer markedly thinned the lipid bilayer which may facilitate substrate translocation. The pore of the nonamer was occupied by a phospholipid layer consisting of [~]6 phospholipids in the absence of substrates and [~]11 phospholipids in their presence. Structurally, the amphipathic helix of TatA were observed to exhibit significant conformational flexibility which appears to facilitate TatA-substrate interactions. In the absence of substrate the TatA nonamer was unstable with its radial architecture collapsing in 200-300 ns. In the presence of substrate, however, the radial geometry of the nonamer persists for at least 1000 ns. Interestingly, in the presence of the smaller substrate OEE17, fewer TatA monomers are retained in a radial geometry then observed in the presence of the larger substrate TorA indicating that the molecularity of the TatA oligomer can adjust to the size of the substrate. Specific hydrophilic residues of the TatA amphipathic helixes were found to interact with both substrate molecules, and these form quite stable charge-pair or hydrogen-bonding interactions. While the substrate proteins were initially placed adjacent to the amphipathic helixes of the nonamer, during the simulation trajectories the substrates moved to a more central position adjacent to, and partially entering, the oligomer pore. Concomitantly, the oligomer was observed to lose phospholipids. These latter observations may constitute a glimpse of the initial stages of protein translocation.

biochemistry↗

bioRxiv2025

Targeted ortholog search in unannotated genome assemblies with fDOG-Assembly

Whole genome shotgun sequencing and assembly is routine. However, identifying protein-coding genes in newly assembled genomes remains complex, time-consuming, and labour-intensive. Therefore, most eukaryotic genome assemblies in public databases lack gene annotations reducing their value for evolutionary and functional genomics. Here, we present fDOG-Assembly, a novel tool for targeted, feature architecture-aware ortholog searches directly in unannotated genome assemblies. Benchmarking shows that fDOG-Assembly performs similarly to BUSCO and Compleasm in ortholog identification while offering the advantage of not being restricted to universal single-copy genes. Applied to identify orthologs of 5,000 human genes in rat and Nematostella vectensis, fDOG-Assembly approaches the performance of traditional ortholog search tools that rely on pre-annotated proteomes. Importantly, it can recover orthologs missed by conventional methods because of incomplete gene annotations, helping to fill gaps in phylogenetic profiles. As a case study, we screened 176 soil invertebrate genome assemblies for genes involved in antibacterial compound production. We found that orthologs of {beta}-lactam biosynthesis genes are widespread in springtails, with individual species possessing nearly complete cephamycin biosynthetic gene sets, suggesting they may represent previously unrecognized natural producers of {beta}-lactam antibiotics. Overall, fDOG-Assembly is a powerful resource for orthology-based analyses of the rapidly growing collection of unannotated genome assemblies.

bioinformatics↗

bioRxiv2025

A leaf phenomics approach to estimating below-ground traits in North American Licorice

Premise of the studyThousands of years of selective breeding has prioritized above-ground yield, with little regard for changes happening below-ground. Despite their central role in plant success and resilience, our knowledge of roots lags behind above-ground structures. Accurately phenotyping root traits is often labor-intensive, expensive, and destructive. In order to advance understanding of the fundamental biology underlying root systems, and to integrate hard-to-measure root traits into breeding programs, high-throughput non-destructive methods are required. MethodsThis study uses American licorice (Glycyrrhiza lepidota Pursh.), a perennial legume with a rich ethnobotanical history, as a model to investigate root system phenotypes. We assess root traits across multiple populations, analyze relationships between above- and below-ground phenotypes, and test the use of multidimensional leaf traits, including spectral reflectance, in predicting root traits. Key resultsAmerican licorice displays significant variation in root traits across source populations and strong correlations between above- and below-ground traits. Leaf spectral reflectance and elemental composition show promise in modeling below-ground traits, though the isometric relationship between plant size and root traits complicates model accuracy. ConclusionsThese findings demonstrate the use of high-dimensional leaf traits as a proxy for root traits, with potential applications for understanding foundational questions in plant biology and in breeding programs targeting the below-ground structures of perennial herbaceous species. Further optimization and larger studies are needed to improve predictive models.

plant biology↗

bioRxiv2025

High-resolution transcriptomic profiling of the aortic cellular landscape during hypertension reveals novel drivers of vascular fibrosis

BackgroundAortic stiffening is a consequence of hypertension and a major contributor to end organ damage. A key driver of aortic stiffening is fibrosis involving the excess production of extracellular matrix (ECM) proteins such as collagen, fibronectin and laminin. The present study aimed to identify the cell types and signalling mechanisms that contribute to aortic fibrosis in hypertension. Methods and ResultsMale C57BL/6 mice (10-12-week-old) were randomly assigned to a 28-day angiotensin II (0.7 mg/kg/day) or vehicle (saline) infusion via osmotic minipump (s.c.). At endpoint, scRNA-seq analysis of 26,196 cells recovered all major aortic cell populations. Among these, fibroblasts exhibited the greatest heterogeneity and shift in gene expression after angiotensin II compared to all other cell types. Gene ontology analyses revealed that after angiotensin II treatment, a particular subcluster of fibroblasts (Fibro-Cthrc1) - characterised by its high expression of Cthrc1 - was especially fibrogenic. Fibro-Cthrc1 cells were nearly undetectable in aortas from vehicle-infused mice. Transcripts relating to ECM remodelling (Thbs2, Cdh11 and Postn) and collagen production (specifically collagen type I, III and V) were more highly enriched in Fibro-Cthrc1 compared to other fibroblasts within hypertensive aortas. Moreover, GO terms corresponding to profibrotic signalling pathways (i.e., cell adhesion, extracellular matrix organisation and collagen fibril organisation) were significantly enriched in Fibro-Cthrc1. Spatial transcriptomics and immunohistochemistry confirmed the presence of Fibro-Cthrc1 in the adventitial layer of angiotensin II-infused but not vehicle-infused mice. Finally, analysis of plasma analytes in approximately 24,000 participants of the UK Biobank collection revealed CTHRC1 to be strongly associated with raised systolic blood pressure and pulse pressure, and a strong predictor of the risk of developing hypertension over a 15-year follow-up. ConclusionOur study identifies a novel fibroblast subcluster, Fibro-Cthrc1, as a potential driver of aortic fibrosis and stiffening in hypertension. This cluster is absent in normotensive aortas, suggesting that targeting Fibro-Cthrc1 therapeutically could prevent aortic fibrosis and its associated hypertensive end-organ damage. Notably, such an approach may avoid compromising physiological extracellular matrix production and vessel integrity. Translational perspectiveAortic stiffening is a hallmark of hypertension resulting from functional (vasoconstriction) and structural (extracellular matrix remodelling) alterations of the vessel wall. While several antihypertensive medications address functional changes, no therapies directly target the causes of the structural remodelling. The therapeutic challenge is to distinguish between physiological and pathological extracellular matrix remodelling. This study identifies a novel highly profibrotic fibroblast cell population (Fibro-Cthrc1) present in aortas from hypertensive, but not normotensive mice. This raises the possibility that Fibro-Cthrc1 may be a key driver of aortic stiffening and a promising future therapeutic target.

physiology↗

bioRxiv2025

Biaxial testing and sensory texture evaluation of plant-based and animal deli meat

Animal agriculture is one of the largest contributors to global carbon emissions. Plant-based meats offer a sustainable alternative to animal meat; yet, people are reluctant to switch their diets and spending habits, in large due to the taste and texture of plant-based meats. Deli meat is a convenient form of protein commonly used in sandwiches, yet little is known about its material or sensory properties. Here we performed biaxial testing with multiple different stretch ratios of four plant-based and four animal deli meats and fit accurate material models to the resulting stress-stretch data. Strikingly, the plant-based products, turkey, ham, deli, and prosciutto, with stiffnesses of 378 {+/-} 15 kPa, 343 {+/-} 62 kPa, 213 {+/-} 25 kPa, and 113 {+/-} 56 kPa, were more than twice as stiff as their animal counterparts, turkey, chicken, ham, and prosciutto, with 134 {+/-} 46 kPa, 117 {+/-} 17 kPa, 117 {+/-} 21 kPa, and 49 {+/-} 21 kPa. In a complementary sensory texture survey, n = 18 participants were able to correlate the physical stiffness with the sensory brittleness, with Spearmans correlation coefficient of{rho} = 0.857 and p = 0.011, but not with the sensory softness or hardness. Notably, the participants perceived all four plant-based products as less fibrous, less moist, and less meaty than the four animal products. Our study confirms the common belief that plant-based products struggle to meet the physical and sensory signature of animal deli meats. We anticipate that integrating rigorous mechanical testing, physics-based modeling, and sensory texture surveys could shape the path towards designing delicious, nutritious, and environmentally friendly meats that mimic the texture and mouthfeel of animal products and are healthy for people and for the planet. Data and code are freely available at https://github.com/LivingMatterLab/CANN.

bioengineering↗

bioRxiv2025

Tahoe-100M: A Giga-Scale Single-Cell Perturbation Atlas for Context-Dependent Gene Function and Cellular Modeling

Building predictive models of the cell requires systematically mapping how perturbations reshape each cells state, function, and behavior. Here, we present Tahoe-100M, a giga-scale single-cell atlas of 100 million transcriptomic profiles measuring how each of 1,100 small-molecule perturbations impact cells across 50 cancer cell lines. Our high-throughput Mosaic platform, composed of a highly diverse and optimally balanced "cell village", reduces batch effects and enables parallel profiling of thousands of conditions at single-cell resolution at an unprecedented scale. As the largest single-cell dataset to date, Tahoe-100M enables artificial-intelligence (AI)-driven models to learn context-dependent functions, capturing fundamental principles of gene regulation and network dynamics. Although we leverage cancer models and pharmacological compounds to create this resource, Tahoe-100M is fundamentally designed as a broadly applicable perturbation atlas and supports deeper insights into cell biology across multiple tissues and contexts. By publicly releasing this atlas, we aim to accelerate the creation and development of robust AI frameworks for systems biology, ultimately improving our ability to predict and manipulate cellular behaviors across a wide range of applications.

genomics↗

bioRxiv2024

Tracing the taxonomic distribution of plant cell wall degrading enzymes across the tree of life using feature architecture aware orthology assignments

The decomposition of plant material is a key driver of the global carbon cycle, traditionally attributed to fungi and bacteria. However, some invertebrates also possess orthologs to bacterial or fungal cellulolytic enzymes, likely acquired via horizontal gene transfer. This reticulated mode of evolution necessitates ortholog searches in large taxon sets to comprehensively map the repertoire of plant cell wall degrading enzymes (PCDs) across the tree of life, a task surpassing capacities of current software. Here, we use fDOG, a novel profile-based ortholog search tool to trace 235 potential PCDs across more than 18,000 taxa. fDOG allows to start the ortholog search from a single protein sequence as a seed, it performs on par with state-of-the-art software that require the comparison of entire proteomes, and it is unique in routinely scoring protein feature architecture differences between the seed protein and its orthologs. Visualizing the presence-absence patterns of PCD orthologs using a UMAP highlights taxa where recent changes in the enzyme repertoire indicate a change in lifestyle. Three invertebrates have a particularly rich set of PCD orthologs encoded in their genome. Only few of the orthologs show differing protein feature architectures relative to the seed that suggest functional modifications. Thus, the corresponding species represent lineages within the invertebrates that may contribute to the global carbon cycle. This study shows how fDOG can be used to create a multi-scale view on the taxonomic distribution of a metabolic capacity that ranges from tree of life-wide surveys to individual feature architecture changes within a species.

bioinformatics↗

bioRxiv2024

Global remodeling of ADP-ribosylation by PARP1 suppresses influenza A virus infection

ADP-ribosylation is a highly dynamic and fully reversible post-translational modification performed by poly(ADP-ribose) polymerases (PARPs) that modulates protein function, abundance, localization and turnover. Here we show that influenza A virus infection causes a rapid and dramatic upregulation of global ADP-ribosylation that inhibits viral replication. Mass spectrometry defined for the first time the global ADP-ribosylome during infection, creating an infection-specific profile with almost 4,300 modification sites on [~]1,080 host proteins, as well as over 100 modification sites on viral proteins. Our data indicate that the global increase likely reflects a change in the form of ADP-ribosylation rather than modification of new targets. Functional assays demonstrated that modification of the viral replication machinery antagonizes its activity and further revealed that the anti-viral activity of PARPs and ADP-ribosylation is counteracted by the influenza A virus protein NS1, assigning a new activity to the primary viral antagonist of innate immunity. We identified PARP1 as the enzyme producing the majority of poly(ADP-ribose) present during infection. Influenza A virus replicated faster in cells lacking PARP1, linking PARP1 and ADP-ribosylation to the anti-viral phenotype. Together, these data establish ADP-ribosylation as an anti-viral innate immune-like response to viral infection antagonized by a previously unknown activity of NS1.

microbiology↗

bioRxiv2024

Early NK-cell and T-cell dysfunction marks progression to severe dengue in patients with obesity and healthy weight

Dengue is a mosquito-borne virus infection affecting half of the worlds population for which therapies are lacking. The role of T and NK-cells in protection/immunopathogenesis remains unclear for dengue. We performed a longitudinal phenotypic, functional and transcriptional analyses of T and NK-cells in 124 dengue patients using flow cytometry and single-cell RNA-sequencing. We show that T/NK-cell signatures early in infection discriminate patients who will progress to severe dengue (SD) from those who do not. In patients with overweight/obesity these signatures are exacerbated compared to healthy weight patients, supporting their increased susceptibility to SD. In SD, CD4+/CD8+ T-cells and NK-cells display increased co-inhibitory receptor expression and decreased cytotoxic capacity compared to non-SD. Furthermore, type-I Interferon signalling is downregulated in SD, suggesting defective virus-sensing mechanisms may underlie NK/T-cell dysfunction. We propose that dysfunctional "professional killer" T/NK-cells underpin dengue pathogenesis. Our findings pave the way for the evaluation of immunomodulatory therapies for dengue.

immunology↗

bioRxiv2024

SIRT6 loss causes intervertebral disc degeneration in mice by promoting senescence and SASP status

Intervertebral disc degeneration is a major risk factor contributing to chronic low back and neck pain. While the etiological factors for disc degeneration vary, age is still one of the most important risk factors. Recent studies have shown the promising role of SIRT6 in mammalian aging and skeletal tissue health, however its role in the intervertebral disc health remains unexplored. We investigated the contribution of SIRT6 to disc health by studying the age-dependent spinal phenotype of mice with conditional deletion of Sirt6 in the disc (AcanCreERT2; Sirt6fl/fl). Histological studies showed a degenerative phenotype in knockout mice compared to Sirt6fl/fl control mice at 12 months which became pronounced at 24 months. RNA-Seq analysis of NP and AF tissues, quantitative histone analysis, and in vitro multiomics employing RNA-seq with ATAC-seq revealed that SIRT6-loss resulted in changes in acetylation and methylation status of specific Histone 3 lysine residues, thereby affecting DNA accessibility and transcriptomic landscape. A decrease in autophagy and an increase in DNA damage were also noted in Sirt6-deficient cells. Further mechanistic insights revealed that loss of SIRT6 increased senescence and SASP burden in the disc characterized by increased p21, {gamma}H2AX, IL-6, and TGF-{beta} abundance. Taken together our study highlights the contribution of SIRT6 in modulating DNA damage, autophagy and cell senescence, and its importance in maintaining disc health during aging thereby underscoring it as a potential therapeutic target to treat intervertebral disc degeneration.

molecular biology↗

bioRxiv2024

Impact of Parental Time-Restricted Feeding on Offspring Metabolic Phenotypic Traits

A substantial body of research elucidates the mechanisms and health advantages associated with intermittent fasting (IF). However, the impact of parental IF on offspring remains unclear. Through an investigation involving four IF and ad libitum combinations of parental mating groups, we demonstrate that parental IF (daily time-restricted feeding) influences offsprings metabolic health indicators in male and female offspring in distinct ways. We found that when both parents are on IF their offspring exhibit protection against the adverse effects of a high-fat, high-sugar, and high-salt diet in a sex-specific manner. This study underscores the potential significance of parental lifestyle modifications involving dietary restriction for the metabolic status of their children and their risk for obesity and diabetes.

genetics↗

bioRxiv2024

MetaIBS: large-scale amplicon-based meta analysis of irritable bowel syndrome

BackgroundIrritable Bowel Syndrome (IBS) is a chronic functional bowel disorder causing abdominal discomfort, as well as transit deregulation with constipation and/or diarrhea. The pathophysiology of IBS is poorly understood and believed to be multifactorial. The role of gut microbiota in IBS has been investigated in several case-control studies, in particular via 16S rRNA amplicon sequencing surveys. These studies, however, have not yet led to a consistent picture of significant changes in gut microbial compositions across health and disease. One key bottleneck is the modest cohort sizes of most individual studies and a high diversity of experimental, bioinformatics, and statistical analysis approaches across studies. ResultsWe address these shortcomings by presenting MetaIBS, an open-access data repository and associated meta-analysis workflow of thirteen 16S rRNA amplicon datasets comprising both fecal matter and sigmoid biopsy samples spanning {bsim}2,500 IBS and healthy individuals. MetaIBS includes a tailored computational framework that (i) enables coherent de novo processing and taxonomic assignments of the raw 16S rRNA amplicon reads across experimental protocols and sequencing technologies, and (ii) statistical workflows for visualization and analysis at different taxonomic ranks and data granularity. Our statistical meta-analysis shows that popular high-level microbiome summary statistics, including Firmicutes/Bacteroidota ratios or diversity indices, are insufficient for reliable discrimination between IBS patients and healthy controls. Fine-grained multi-method differential abundance and classification analysis, however, can identify sets of differentially abundant taxa that replicate across multiple datasets, including Coprococcus eutactus and Alistipes finegoldii. ConclusionsMetaIBS provides a curated and reproducible data and (meta-)analysis resource for amplicon-based IBS research at unprecedented scale. MetaIBS allows assessing the heterogeneity of IBS cohorts across multiple experimental protocols, sample types, and IBS phenotypes. Our framework will likely contribute to more coherent insights into the role of the microbiome in IBS and the discovery of reliable microbial IBS biomarkers for follow-up functional and translational studies.

microbiology↗