Project description:The effects of maternal microbiota on the fetal development was investigated by comparing tissues of fetuses from germ-free (GF) and normal (SPF) murine dams using RNA-seq and non-targeted metabolomics (for metabolomics data, see: https://bmcmicrobiol.biomedcentral.com/articles/10.1186/s12866-022-02457-6). For RNA-seq, two E18.5 fetuses were collected from 6 GF dams and 6 SPF dams, and transcriptomes analyzed by QuantSeq in whole intestine, brain and placenta.
Project description:We leveraged neonatal piglets as a preclinical model for human infants, with a system-level approach that integrates evidence from serum, urine, liver, brain and the gastrointestinal tract (GIT), with the bioactive function of α-lactalbumin, a rich source of tryptophan, in a formula feeding study. Complementing metabolomics data generated throughout the GIT during the early feeding period, we further integrated quantitative serum, liver, brain and urine metabolome data, as well as liver and brain transcriptome data to investigate the metabolic consequences behind the differential responses to diet. Transcriptional and metabolomics analysis revealed an individualized, divergent response to α-lactalbumin linked to either efficient utilization of tryptophan by the host, or production of indole-3-lactate by intestinal microbiota. This variability was further highlighted by differences in metabolic and immunological effects in a tissue-specific manner. Our work highlights the importance of considering the nutrition-microbiota-host metabolism axis to optimize the phenotypic response of a diet.
Project description:Total brain was collected from newborn rats that were growth-restricted obtained by feeding the females a low-protein diet during pregnancy. The model was extensively described in Buffat et al, J. Pathology 2007, and Zana-Taieb et al, J. Pathology, 2015.
Project description:Caloric restriction (CR) extends organismal life- and health-span by improving glucose homeostasis. How CR affect the structure-function of pancreatic beta cells remains unknown. We used single nucleus transcriptomics to show that CR increases the expression of genes for beta cell identity, protein processing, and organelle homeostasis. Gene regulatory network analysis reveal that CR activates transcription factors important for beta cell identity and homeostasis, while imaging metabolomics demonstrates that CR beta cells are more energetically competent. In fact, high-resolution microscopy show that CR reduces beta cell mitophagy to increase mitochondria mass and the potential for ATP generation. However, CR beta cells have impaired adaptive pro liferation in response to high fat diet feeding. Finally, we show that long-term CR delays the onset of beta cell aging and promotes cell longevity by reducing beta cell turnover. Therefore, CR could be a feasible approach to preserve compromised beta cell structure-function during aging and diabetes. 27 diabetes.