Project description:Triple-negative breast cancer (TNBC) presents a significant challenge in women’s health due to its aggressive phenotype and the absence of targeted therapeutic options. β-Elemene, a sesquiterpene isolated from Curcuma wenyujin, has demonstrated clinical benefits against TNBC; however, its mechanisms of action, particularly with respect to the immune and metabolic tumor microenvironment, remain poorly characterized. In this study, we employed single-cell RNA sequencing and untargeted metabolomics to investigate how β-elemene reshapes the cellular and metabolic landscape of TNBC using a 4T1 orthotopic mouse model. Our findings are expected to provide the first comprehensive elucidation of β-elemene’s dual immunomodulatory and metabolic effects in TNBC, highlighting the potential of natural compounds to enhance antitumor immunity.
Project description:Many previous studies had revealed that gastrointestinal microbiome is changed compositionally and ecologically in patients with colorectal cancer comparing with healthy population. These finding provide us with a new sight to take advantage of gut microbiota. The current study aims to explore new potential biomarkers for early screening and prognostic prediction of colorectal cancer and colorectal polyps by analyzing metagenomics and metabolomics of gut microbiota.
Project description:Urolithins are a class of bioactive metabolites derived from the metabolism of dietary ellagitannins by the human gut microbiota. In the gut, urolithins are dehydroxylated regioselectively based on microbiota composition and activity. A single 9-hydroxy urolithin dehydroxylase (ucd) operon in gut resident Enterocloster species has been described to date; however, most enzymes in the urolithin metabolic pathway remain uncharacterized. Here, we investigate urolithin cross-feeding between members of the gut microbiota and discover a novel urolithin dehydroxylase in a subset of Enterocloster species. We show that urolithin intermediates, released by gut resident Gordonibacter species during ellagic acid metabolism, are dehydroxylated at both the 9- and 10-positions by E. asparagiformis, E. citroniae, and E. pacaense, but not E. bolteae. Using untargeted proteomics, we uncover a 10-hydroxy urolithin dehydroxylase operon, termed uxd, responsible for these species-specific differences in urolithin metabolism. By inducing uxd expression with diverse urolithins, we show that 9-hydroxy urolithins are required for uxd transcription and 10-position dehydroxylation. Collectively, this study reveals some of the genes, proteins, and substrate features underlying differences in urolithin metabolism by the human gut microbiota.
Project description:Maturation of the gut microbiota coincides with neurodevelopmental processes such as myelination, essential for efficient neural signal transmission. While its role in adult prefrontal cortex (PFC) myelination is known, effects on early-life myelin formation, growth, and integrity remain unclear. Here, we track gene expression in the PFC of germ-free (GF) and non-germ-free (conventional) mice. Alongside metabolomics (HP/LC) from the same region across early life development, in males and females. Metabolomics data available here <URL PLACEHOLDER> In GF mice, we observed sex- and age-dependent alterations in pathways linked to neuronal activity and myelination, with myelin-related transcriptomic changes correlating with functional shifts in neurotransmission- and metabolism-related metabolites over time. Myelin growth and integrity were also affected in a sex- and time-dependent manner. As microglia regulate neuronal activity and engulf myelin, we examined microbiota-microglia interactions and found altered expression of genes involved in microglia maturation and synaptic pruning in both species. In zebrafish larvae, the microbiota influenced the spatial distribution of microglia and oligodendrocytes within the brain and spinal cord. These findings reveal conserved microbiota-mediated modulation of neuronal activity, myelination, and glial maturation in early life, providing a foundation for future studies into these mechanisms. These files contain the RNAseq data underlying this study.