Project description:Microbial functions in the host physiology are a result of co-evolution between microbial communities and their hosts. Here we show that cold exposure leads to marked shift of the microbiota composition, referred to as cold microbiota. Transplantation of the cold microbiota to germ-free mice is sufficient to increase the insulin sensitivity of the host, and enable complete tolerance to cold partly by promoting the white fat browning, leading to increased energy expenditure and fat loss. During prolonged cold however, the body weight loss is attenuated, caused by adaptive mechanisms maximising caloric uptake and increasing intestinal, villi and microvilli lengths. This increased absorptive surface is promoted by the cold microbiota - effect that can be diminished by co-transplanting the most downregulated bacterial strain from the Verrucomicrobia phylum, Akkermansia muciniphila, during the cold microbiota transfer. Our results demonstrate the microbiota as a key factor orchestrating the overall energy homeostasis during increased demand.
Project description:Microbial functions in the host physiology are a result of co-evolution between microbial communities and their hosts. Here we show that cold exposure leads to marked shift of the microbiota composition, referred to as cold microbiota. Transplantation of the cold microbiota to germ-free mice is sufficient to increase the insulin sensitivity of the host, and enable complete tolerance to cold partly by promoting the white fat browning, leading to increased energy expenditure and fat loss. During prolonged cold however, the body weight loss is attenuated, caused by adaptive mechanisms maximising caloric uptake and increasing intestinal, villi and microvilli lengths. This increased absorptive surface is promoted by the cold microbiota - effect that can be diminished by co-transplanting the most downregulated bacterial strain from the Verrucomicrobia phylum, Akkermansia muciniphila, during the cold microbiota transfer. Our results demonstrate the microbiota as a key factor orchestrating the overall energy homeostasis during increased demand.
Project description:Purpose: NGS was used to determine if a distinct transcriptomic profile is observed among the experimental mice fed four different dietary components. Methods: We carried out RNA-Seq analysis of ileum tissue from 6 weeks male mice ad libitum fed for 10 weeks a high liquid sugar (23% (w/v)) or/and high fat (60% Kcal from fat) diet. The combined effect of sugar drink and high fat diet (HF-Sugar) was compared with sugar drink only (NF-Sugar), or high fat diet only (HF), or control diet that was plain water and normal fat diet (NF). Results: RNA-Seq revealed sample-specific clusters that included genes responding to each experimental diet. We found only addition of sugar drink to high fat group (HF-Sugar) not NF-Sugar and HF, there was a significant enrichment in biological functions relating to Inflammatory/Immune Responses, especially including dendritic cell (DC) and T cell related signaling pathway. Conclusions: Taken together, our data demonstrate that sugar drink synergistically promotes and exacerbates inflammatory responses driven by the high fat diet.
Project description:The mammalian gastrointestinal tract contains a diverse ecosystem of microbial species collectively making up the gut microbiome. Emerging evidence highlights a critical relationship between gut microbiota and neurocognitive development. Consumption of unhealthy yet palatable dietary factors associated with obesity and metabolic dysfunction (e.g., saturated fat, added sugar) produces microbiota dysbiosis and negatively impacts neurocognitive function, particularly when consumed during early life developmental periods. Here we explore whether excessive early life consumption of added sugars negatively impacts neurocognitive development via the gut microbiome. Using a rodent model of habitual sugar-sweetened beverage (SSB) consumption during the adolescent stage of development, we first show that excessive early life sugar intake impairs hippocampal-dependent memory function when tested during adulthood while preserving other neurocognitive domains. Gut microbiome genomic sequencing analyses reveal that early life SSB consumption alters the abundance of various bacterial populations, including elevations in operational taxonomic units within the genus Parabacteroides (P. distasonis and P. johnsonii) whose abundance negatively correlated with memory task performance. Additional results reveal that in vivo Parabacteroides enrichment of cultured P. distasonis and P. johnsonii bacterial species in adolescent rats severely impairs memory function during adulthood. Hippocampus transcriptome analyses identify gene expression alterations in neurotransmitter synaptic signaling, intracellular kinase signaling, metabolic function, neurodegenerative disease, and dopaminergic synaptic signaling-associated pathways as potential mechanisms linking microbiome outcomes with memory impairment. Collectively these results identify microbiota dysbiosis as a mechanism through which early life unhealthy dietary patterns negatively impact neurocognitive outcomes.
Project description:A high-sugar diet induces lifestyle-associated metabolic diseases, such as obesity and diabetes, which may underlie the pro-tumor effects of a high-sugar diet. We supplied GL261 syngeneic glioblastoma (GBM) model mice with a short-term high-glucose diet (HGD) and found an increased survival rate with no evidence of metabolic disease. Modulation of the gut microbiota by an HGD was critical for enhancing the anti-tumor immune response. Single-cell RNA sequencing showed that modulation of the gut microbiota by an HGD increased the T cell-mediated anti-tumor immune response in GBM mice. We found that the cytotoxic CD4+ T cell population in GBM mice increased due to synergy with anti-PD-1 immune checkpoint inhibitors, but this depended on an HGD. Thus, we determined that an HGD enhanced anti-tumor immune responses in GBM mice through changes in the gut microbiota and suggest that the role of an HGD in GBM should be re-examined.
Project description:Sensitivity of murine offspring’s oocytes to a maternal high-fat/high-sugar (HF/HS) diet and how preconception care interventions (diet normalization (DN) or caloric restriction (CR)) might influence this. A proteomic insight.
