A5065853254- Gut microbiota and health
- Probiotics and Fermented Foods
- Clostridium difficile and Clostridium perfringens research
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Epigenetics and DNA Methylation
- Viral gastroenteritis research and epidemiology
- Immune cells in cancer
- Microscopic Colitis
- Immune Response and Inflammation
- Eating Disorders and Behaviors
- Advanced Proteomics Techniques and Applications
- Gastrointestinal motility and disorders
- Child Nutrition and Feeding Issues
- Streptococcal Infections and Treatments
- Antimicrobial Resistance in Staphylococcus
- Pediatric health and respiratory diseases
- RNA and protein synthesis mechanisms
- Health and Medical Research Impacts
- Single-cell and spatial transcriptomics
- Salmonella and Campylobacter epidemiology
- Antimicrobial Peptides and Activities
- Infective Endocarditis Diagnosis and Management
- Helicobacter pylori-related gastroenterology studies
University of Cambridge
2019-2025
MRC Epidemiology Unit
2021-2024
Rockefeller University
2015-2019
Memorial Sloan Kettering Cancer Center
2007-2015
Howard Hughes Medical Institute
2015
Human health and disease have increasingly been shown to be impacted by the gut microbiota, mouse models are essential for investigating these effects. However, compositions of human microbiotas distinct, limiting translation microbiota research between hosts. To address this, we constructed Mouse Gastrointestinal Bacteria Catalogue (MGBC), a repository 26,640 high-quality microbiota-derived bacterial genomes. This catalog enables species-level analyses mapping functions interest identifying...
Abstract Experimental mouse models are central to basic biomedical research; however, variability exists across genetically identical mice and facilities making comparisons difficult. Whether specific indigenous gut bacteria drive immunophenotypic in of human disease remains poorly understood. We performed a large-scale experiment using 579 laboratory from single animal facility, designed identify the causes widely used dextran sulphate sodium model inflammatory bowel disease. Commonly...
The gut microbiome modulates immunotherapy treatment responses, and this may explain why immune checkpoint inhibitors, such as anti-PD-1, are only effective in some patients. Previous studies correlated lipopolysaccharide (LPS)-producing microbes with poorer prognosis; however, LPS from diverse bacterial species can range immunostimulatory to inhibitory. Here, by functionally analysing faecal metagenomes 112 patients melanoma, we found that a subset of LPS-producing bacteria encoding...
CTLA-4, an Ig superfamily molecule with homology to CD28, is one of the most potent negative regulators T-cell responses. In vivo blockade CTLA-4 exacerbates autoimmunity, enhances tumor-specific responses, and may inhibit induction anergy. Clinical trials CTLA-4–blocking antibodies augment responses malignant melanoma are at advanced stage; however, little known about effects on memory CD8 + formation maintenance long-term memory. our studies, we show that during in Listeria monocytogenes...
The intestinal microbiome modulates host susceptibility to enteric pathogens, but the specific protective factors and mechanisms of individual bacterial species are not fully characterized. We show that secreted antigen A (SagA) from Enterococcus faecium is sufficient protect Caenorhabditis elegans against Salmonella pathogenesis by promoting pathogen tolerance. NlpC/p60 peptidoglycan hydrolase activity SagA required generates muramyl-peptide fragments C. in a tol-1-dependent manner. can...
Conventional dendritic cells (cDCs) play an essential role in host immunity by initiating adaptive T cell responses and serving as innate immune sensors. Although both functions of cDCs are well documented, their relative importance maintaining homeostasis is poorly understood. To examine the significance cDC-initiated homeostasis, independent activities, we generated a cDC-specific Cre mouse crossed it to floxed MHC class II (MHCII) mouse. Absence MHCII on resulted chronic intestinal...
We discovered that Enterococcus faecium (E. faecium), a ubiquitous commensal bacterium, and its secreted peptidoglycan hydrolase (SagA) were sufficient to enhance intestinal barrier function pathogen tolerance, but the precise biochemical mechanism was unknown. Here we show E. has unique composition remodeling activity through SagA, which generates smaller muropeptides more effectively activates nucleotide-binding oligomerization domain-containing protein 2 (NOD2) in mammalian cells. Our...
A secreted bacterial protein protects worms and mice from Salmonella pathogenesis.
During primary Ag encounter, T cells receive numerous positive and negative signals that control their proliferation, function, differentiation, but how these are integrated to modulate cell memory has not been fully characterized. In studies, we demonstrate combining seemingly opposite signals, CTLA-4 blockade rapamycin-mediated mammalian target of rapamycin inhibition, during in vivo priming leads both an increase the frequency CD8(+) improved responses tumors bacterial challenges. This...
Abstract Background Promoting resistance to enteric pathogen infection is a core function of the gut microbiota; however, many specific host–commensal interactions that mediate this protection remain uncharacterised. To address knowledge gap, we monocolonised germ-free mice with mouse-derived commensal microbes screen for microbiota-induced Salmonella Typhimurium infection. Results We identified Enterocloster clostridioformis as protective species against S. E. selectively upregulates...
Abstract Regulation of CD8 T cell expansion and contraction is essential for successful immune defense against intracellular pathogens. IL-10 a regulatory cytokine that can restrict responses by inhibiting APC functions. IL-10, however, also have direct effects on cells. Although blockade or genetic deletion enhances cell-mediated resistance to infections, the extent which limits in vivo function activation/proliferation remains unknown. Herein, we demonstrate primary memory following...
Abstract Immune checkpoint inhibitors (ICI), such as anti-PD-1, have revolutionized cancer treatment, but they are only effective for a minority of patients. The gut microbiome plays crucial role in modulating immunotherapy treatment responses, and previous studies correlated lipopolysaccharide (LPS)-producing microbes with poorer prognosis. However, LPS from diverse bacterial species activities ranging immunostimulatory to inhibitory. By functionally analyzing fecal metagenomes 112 melanoma...
The mammalian gut microbiota consists of hundreds anaerobic bacterial species that shape intestinal homeostasis and influence host immune responses. Although the causal roles specific human in health disease are emerging, role indigenous bacteria driving immunophenotypic variability mouse models remains poorly understood. We performed a large-scale experiment using 579 laboratory mice designed to identify validate causes widely used dextran sulphate sodium (DSS) model inflammatory bowel...
Summary Intestinal intraepithelial lymphocytes (IELs) are located at the critical interface between intestinal lumen, which is chronically exposed to food and microbes, core of body. Using high-resolution microscopy techniques intersectional genetic tools, we investigated nature IEL responses luminal microbes. We observed that TCRγδ IELs exhibit distinct location movement patterns in epithelial compartment were microbiota-dependent quickly altered upon enteric infections. These...
Abstract Mouse models are essential for biomedical science and drug discovery, yet it is not known how the bacteria in mouse microbiota – important determinants of phenotypes health disease –affect their relevance to human disease. To interrogate taxonomic functional differences between gut microbiotas, we developed Microbial Genome Collection (MMGC), a compilation 276 genomes from cultured isolates 45,218 metagenome-assembled (MAGs) 1,960 publicly available metagenomes. The MMGC reveals...
Abstract Promoting resistance to enteric pathogen infection is a core function of the gut microbiota. However, many host-commensal interactions that likely mediate this protection remain uncharacterised. By screening gnotobiotic mice monocolonised with range mouse-derived commensal bacteria we have identified Enterocloster clostridioformis as protective species against Salmonella Typhimurium infection. Unlike colonisation induced by some bacteria, E. selectively induces previously...