Biology subjects

Swann, J. R.

Publications and source records attributed to Swann, J. R..

5 recordsLinked to original sources

bioRxiv2026

Birth by Cesarean Section Remodels Neonatal Brain Barriers and Associated Immune and Metabolic Pathways in Mice

Delivery mode shapes early-life physiology through multiple pathways, including stress and hormonal signalling, neonatal oxygenation, and exposure to maternal microbes. Cesarean section (CS) bypasses several of these processes and has been associated with altered immune maturation and neurodevelopmental outcomes in humans and animal models. Given that CS is known to disrupt gut barrier integrity and that gut and brain barriers operate as a coordinated network, we investigated whether CS affects early postnatal brain barriers. Using a mouse model, we compared CS-delivered pups to vaginally born (VB) controls at postnatal days 8-9. Brain barrier permeability and structure were assessed using tracer extravasation and vascular and tight junction analyses, choroid plexus immune populations were profiled, and metabolomics was performed in cortex and plasma. The blood-brain barrier in the medial prefrontal cortex was mostly preserved. In contrast, the blood-cerebrospinal fluid barrier (BCSFB) exhibited structural alterations in vascular and epithelial tight junction compartments. These changes were accompanied by immune remodelling, including expansion of antigen-presenting border-associated macrophages and reduced parenchymal microglia density. CS delivery increased brain tracer accumulation, consistent with altered barrier function during this developmental window. Metabolomic analyses revealed lower levels of key brain metabolites, including N-acetylaspartate, a marker of neuronal metabolic state. Together, these findings demonstrate that CS delivery induces early alterations in brain barrier function, BCSFB structure, the immune landscape, and metabolic profiles in mice. This identifies delivery mode as a key perinatal variable shaping neonatal brain physiology and establishes a framework for dissecting how birth context may influence long-term neurodevelopmental trajectories. HIGHLIGHTSO_LICesarean section (CS) reveals the neonatal BCSFB as a vulnerable interface shaped by birth mode C_LIO_LICS increases brain tracer accumulation despite largely preserved BBB structural markers at the mPFC C_LIO_LICS induces region-specific vascular, epithelial, and immune remodeling in the choroid plexus C_LIO_LICesarean birth increases the proportion of antigen-presenting choroid plexus macrophages C_LIO_LICS shifts mPFC metabolic profiles, including reduced N-acetylaspartate and malate C_LI

neuroscience↗

bioRxiv2021

Rhythmicity of Intestinal IgA Responses Confers Oscillatory Commensal Microbiota Mutualism

Mutualistic interactions with the commensal microbiota are enforced through a range of immune responses that confer metabolic benefits for the host and ensure tissue health and homeostasis. Immunoglobulin (Ig)A responses directly determine the composition of commensal species that colonize the intestinal tract but require significant metabolic resources to fuel antibody production by tissue-resident plasma cells. Here we demonstrate IgA responses are subject to diurnal regulation by dietary-derived metabolic cues and a cell-intrinsic circadian clock. Rhythmicity in IgA secretion conferred oscillatory patterns on the commensal microbial community and its associated metabolic activity, resulting in changes to metabolite availability over the course of the circadian day. Our findings suggest circadian networks comprising intestinal IgA, the diet and the microbiota align to ensure metabolic health. One-Sentence SummaryWe demonstrate diurnal rhythms in intestinal IgA act to cross-regulate oscillations in the abundance of commensal microbes to foster mutualism.

immunology↗

bioRxiv2019

Faecal virome transplantation decrease symptoms of type-2-diabetes and obesity in a murine model

ObjectiveDevelopment of obesity and type-2-diabetes (T2D) are associated with gut microbiota (GM) changes. The gut viral community is predominated by bacteriophages (phages), which are viruses that attack bacteria in a host-specific manner. As a proof-of-concept we demonstrate the efficacy of faecal virome transplantation (FVT) from lean donors for shifting the phenotype of obese mice into closer resemblance of lean mice.\n\nDesignThe FVT consisted of viromes extracted from the caecal content of mice fed a low-fat (LF) diet for fourteen weeks. Male C57BL/6NTac mice were divided into five groups: LF (as control), high-fat diet (HF), HF+Ampicillin (Amp), HF+Amp+FVT and HF+FVT. At week six and seven of the study the HF+FVT and HF+Amp+FVT mice were treated with FVT by oral gavage. The Amp groups were treated with ampicillin 24 h prior to first FVT treatment.\n\nResultsSix weeks after first FVT the HF+FVT mice showed a significant decrease in weight gain compared to the HF group. Further, glucose tolerance was comparable between the lean LF and HF+FVT mice, while the other HF groups all had impaired glucose tolerance. These observations were supported by significant shifts in GM composition, blood plasma metabolome, and expression levels of genes involved in obesity and T2D development.\n\nConclusionsTransfer of gut viral communities from mice with a lean phenotype into those with an obese phenotype reduce weight gain and normalise blood glucose parameters relative to lean mice. We hypothesise that this effect is mediated via FVT-induced GM changes.\n\nSignificance of this studyWhat is already known about this subject?\n\nO_LIObesity and type-2-diabetes (T2D) are associated with gut microbiota (GM) dysbiosis.\nC_LIO_LIFaecal microbiota transplant from lean donors has previously shown potential in treating obesity and T2D.\nC_LIO_LIPatients suffering from recurrent Clostridium difficile infections (rCDI) have been cured with sterile filtered donor faeces (containing enteric viruses and no bacteria), here defined as faecal virome transplantation (FVT).\nC_LI\n\nWhat are the new findings?\n\nO_LIFVT from lean donors lead to decreased weight gain and normalised blood sugar tolerance in a diet-induced obesity (DIO) mouse model.\nC_LIO_LIFVT significantly changed the bacterial and viral GM component, as well as the plasma metabolome and the expression profiles of obesity and T2D associated genes.\nC_LIO_LIInitial treatment with ampicillin prior FVT seems to counteract the beneficial effects associated with FVT.\nC_LI\n\nHow might it impact on clinical practice in the foreseeable future?\n\nO_LIWe here show a proof-of-concept, providing a solid base for designing a clinical study of FVT targeting obesity and T2D in humans. This is further augmented by the increased safety related to FVT, since bacteria and other microorganisms are removed from the donor faeces, and therefore minimises the risk of disease transmission.\nC_LIO_LIThese findings highlight the potential application of FVT treatment of various diseases related to GM dysbiosis and further support the vital role of the viral community in maintaining and shaping the GM.\nC_LI

microbiology↗

bioRxiv2018

A Novel Mouse Model of Campylobacter jejuni Enteropathy and Diarrhea

Campylobacter infections are among the leading bacterial causes of diarrhea and of environmental enteropathy (EE) and growth failure worldwide. However, the lack of an inexpensive small animal model of enteric disease with Campylobacter has been a major limitation for understanding its pathogenesis, interventions or vaccine development. We describe a robust standard mouse model that can exhibit reproducible bloody diarrhea or growth failure, depending on the zinc or protein deficient diet and on antibiotic alteration of normal microbiota prior to infection. Zinc deficiency and the use of antibiotics create a niche for Campylobacter infection to establish by narrowing the metabolic flexibility of these mice for pathogen clearance and by promoting intestinal and systemic inflammation. Several biomarkers and intestinal pathology in this model also mimic those seen in human disease. This model provides a novel tool to testing specific hypotheses regarding disease pathogenesis as well as vaccine development that is currently in progress.\n\nAuthor SummaryCampylobacter jejuni has been identified as one of the leading causes of enteropathy and diarrhea. In developing countries, these repeated enteric infections often result in growth deficits and cognitive impairment. There is a lack of small animal models of Campylobacter infection. This is a major hurdle in understanding the pathogenesis of Campylobacter infection in order to lead to therapeutic treatments and vaccines. We have developed a highly reproducible mouse model of Campylobacter infection that has clinical outcomes that match those of malnourished children. We hope that these insights into Campylobacter susceptibility will lead to the development of treatments against this major cause of diarrheal illness.

microbiology↗

bioRxiv2018

Metabolic mechanisms of interaction within a defined gut microbiota

Metabolic interactions among species are ubiquitous in nature, and the fitness costs and benefits they impose often reinforce and stabilize them over time. These interactions are of particular importance in the human gut, where they have functions ranging from enhancing digestion to preventing (or exacerbating) infections. The diversity and sheer number of species present lead to the potential for a multitude of metabolic interactions among species to occur. However, identifying the mechanism and consequences of metabolic interactions between even two species is incredibly challenging. Here, we develop, apply, and experimentally test a framework for identifying potential metabolic mechanisms associated with interspecies interactions. We perform pairwise growth and metabolome profiling of co-cultures of strains from the altered Schaedler flora (ASF), a defined murine microbiota. We then apply our novel framework, which we call the Constant Yield Expectation (ConYE) model, to dissect emergent metabolic behaviors that occur in co-culture. Using the ConYE model, we identify and interrogate an amino acid cross-feeding interaction that is likely to confer a growth benefit to one ASF strain (Clostridium sp. ASF356) in co-culture with another strain (Parabacteroides goldsteinii ASF519). We experimentally validate that the proposed interaction leads to a growth benefit for this strain via media supplementation experiments. Our results reveal the type and extent of emergent metabolic behavior in microbial communities and demonstrate how metabolomic data can be used to identify potential metabolic interactions between organisms such as gut microbes. Our in vitro characterization of the ASF strains and interactions between them also enhances our ability to interpret and design experiments that utilize ASF-colonized animals. We anticipate that this work will improve the tractability of studies utilizing mice colonized with the ASF. Here, we focus on growth-modulating interactions, but the framework we develop can be applied to generate specific hypotheses about mechanisms of interspecies interaction involved in any phenotype of interest within a microbial community.

microbiology↗