Biology subjects

Dreger, S. A.

Publications and source records attributed to Dreger, S. A..

4 recordsLinked to original sources

bioRxiv2026

Maternal Gut Microbiota Regulates Neonatal Retinal Angiogenesis Through Lactational Metabolic Signalling

Early-life vascular development is a tightly regulated process that influences organ maturation and long-term cardiometabolic and neurovascular health. While the maternal microbiome is increasingly recognised as a determinant of neonatal immune, metabolic, and neurodevelopmental programming, its role in developmental angiogenesis remains poorly defined. Here, we investigated whether maternal gut microbiota regulates neonatal retinal vascular development through maternally derived metabolic signals. Using antibiotic-induced dysbiosis with a broad-spectrum antibiotic cocktail consisting of vancomycin, neomycin, metronidazole, amphotericin B, and ampicillin (VNMAA), together with germ-free animals, we assessed retinal angiogenesis at postnatal day 6 (P6) and P12. Maternal microbiome depletion significantly delayed retinal vascular extension at P6 and produced persistent abnormalities in P12 retinal vascular architecture, including reduced deep plexus vascular density, altered descending branch density, and reduced branching complexity after normalisation to vessel density. Whole-genome shotgun sequencing demonstrated pronounced remodelling of the maternal caecal microbiome following antibiotic treatment and reciprocal faecal microbiota transplantation (FMT), whereas P12 pup caecal communities were comparatively limited and did not mirror the dramatic restructuring observed in dams. Restoration of the maternal microbiome by FMT rescued neonatal vascular defects, supporting a causal role for maternal microbial state. Untargeted LC-MS metabolomics of maternal milk identified glycerophospholipid metabolism as a prominent microbiome-sensitive pathway. Choline and related lipid metabolites were prioritised as candidate mediators because of their position within this pathway and their biological relevance to membrane metabolism and endothelial function. In vitro endothelial assays demonstrated that choline modulates endothelial viability and promotes tubule formation. Together, these findings identify a maternal microbiota-milk metabolite-vascular axis regulating neonatal retinal angiogenesis and suggest that lactational metabolic signalling may represent an important mechanism through which maternal microbial ecology shapes offspring vascular development.

cell biology↗

bioRxiv2024

Bifidobacterium pseudocatenulatum capsular exopolysaccharide enhances systemic anti-tumour immunity in pre-clinical breast cancer

Gut microbes have merged as powerful regulators of cancer responses, with Bifidobacterium species and strains playing a key role in promoting anti-tumour immunity. While they represent promising candidates for cancer therapeutics, the specific underlying microbial mechanisms driving their efficacy remains poorly understood. In this study, we demonstrate the broad potential of Bifidobacterium species to inhibit breast cancer progression across multiple pre-clinical mouse models. We identify a novel strain, Bifidobacterium pseudocatenulatum 210, which induces systemic anti-tumour immunity and enhances responses to standard-of-care therapies via its cell surface capsular exopolysaccharide (EPS). B. pseudocatenulatum 210 EPS promotes dendritic cell activation and increases systemic cDC1 infiltration, leading to robust CD8+ T cell-mediated anti-tumour activity. Our findings position Bifidobacterium EPS as a novel class of therapeutic compounds with significant potential for cancer treatment.

cancer biology↗

bioRxiv2021

Reciprocal interactions between the gut microbiome and mammary tissue mast cells promote metastatic dissemination of HR+ breast tumors

Establishing commensal dysbiosis, defined as an inflammatory gut microbiome with low biodiversity, prior to breast tumor initiation, enhances early dissemination of hormone-receptor positive (HR+) mammary tumor cells. Here, we sought to define mammary tissue mediators of dysbiosis-induced tumor dissemination. We found that commensal dysbiosis increased both the frequency and profibrogenicity of mast cells in the mammary tissue, a phenotypic change that persisted after tumor implantation. Fibroblast activation and tissue remodeling associate with enhanced breast tumor metastasis. We employed pharmacological and adoptive transfer approaches to demonstrate that mammary tissue mast cells from dysbiotic animals enhances dissemination of HR+ tumor cells. Collagen levels in mammary tissues from HR+ breast cancer patients correlated with mast cell abundance, suggesting clinical relevance of mast cell-mediated fibroblast activation. Together, these data demonstrate that a gut-mast cell axis exists that induces fibroblast activation and orchestrates early dissemination of HR+ breast tumors. SignificanceOur study defines the mechanism by which an inflammatory gut microbiome facilitates HR+ breast tumor cell dissemination. We establish that gut commensal dysbiosis triggers mammary tissue mast cells to facilitate early metastatic dissemination. These findings highlight a novel gut microbiome-innate immune cell axis involved in negative breast cancer outcomes.

cancer biology↗

bioRxiv2020

Antibiotic-induced disturbances of the gut microbiota result in accelerated breast tumour growth via a mast cell-dependent pathway

The diverse community of commensal microbes that comprise the gut microbiota is known to play an integral role in human health, not least through its ability to regulate host immune responses and metabolic pathways. Alterations to the homeostasis of this community, including through the use of broad-spectrum antibiotics, have already been associated with the progression of several cancers, namely melanoma and liver. The aggressive nature of breast cancer (BrCa), largely due to its ability to metastasize early, has ranked the disease with the second highest mortality rate of all cancers globally. Yet the body of research into the complex relationship between the microbiota and BrCa is still limited. This study found that a depletion of the microbiota, through the administration of antibiotics, significantly increased the rate of primary tumour progression in mouse BrCa models. We show that antibiotic-induced microbiota disturbances lead to changes in behaviour of a relatively obscure tumour-immune cell population: mast cells. We observed increases in tumour stroma-associated mast cells in antibiotic treated animals. Moreover, inhibition of mast cell degranulation, via cromolyn, slowed tumour progression in antibiotic treated animals but not in control animals. Thus, it appears that a perturbed microbiota drives stroma-associated mast cell recruitment and activation, which in turn promotes primary tumour growth through an as yet unknown mechanism. One Sentence Summary: We show that breast cancer progression is accelerated through a unique/novel immune response involving mast cells as a result of an antibiotic induced perturbation of the gut microbiota in a mouse model.

cancer biology↗