Biology subjects

Florence, C.

Publications and source records attributed to Florence, C..

2 recordsLinked to original sources

bioRxiv2024

In-depth characterisation of a selection of gut commensal bacteria reveals their functional capacities to metabolise dietary carbohydrates with prebiotic potential

The microbial utilisation of dietary carbohydrates is closely linked to the pivotal role of the gut microbiome in human health. Inherent to the modulation of complex microbial communities, a prebiotic implies the selective utilisation of specific substrate, relying on the metabolic capacities of targeted microbes. In this study, we investigated the metabolic capacities of 17 commensal bacteria of the human gut microbiome toward dietary carbohydrates with prebiotic potential. First, in vitro experiments allowed the classification of bacterial growth and fermentation profiles in response to various carbon sources, including agave inulin, corn fiber, polydextrose and citrus pectin. The influence of phylogenetic affiliation appeared to statistically outweigh carbon sources in determining the degrees of carbohydrate utilisation. Secondly, we narrowed our focus on six commensal bacteria representative of the Bacteroidetes and Firmicutes phyla to perform an untargeted HR-LC/MS metabolomic analysis. Bacteroides xylanisolvens, Bacteroides thetaiotaomicron, Bacteroides intestinalis, Subdoligranulum variabile, Roseburia intestinalis and Eubacterium rectale exhibited distinct metabolomic profiles in response to different carbon sources. The relative abundance of bacterial metabolites was significantly influenced by dietary carbohydrates, with these effects being strain-specific and/or carbohydrate-specific. Particularly, the findings indicated an elevation in short-chain fatty acids and other metabolites, including succinate, gamma-aminobutyric acid, and nicotinic acid. These metabolites were associated with putative health benefits. Finally, an RNA-Seq transcriptomic approach provided deeper insights into the underlying mechanisms of carbohydrate metabolisation. Restricting our focus on four commensal bacteria, including B. xylanisolvens, B. thetaiotaomicron, S. variabile and R. intestinalis, carbon sources did significantly modulate the level of bacterial genes related to the enzymatic machinery involved in the metabolisation of dietary carbohydrates. This study provides a holistic view of the molecular strategies induced during the dynamic interplay between dietary carbohydrates with prebiotic potential and gut commensal bacteria.

microbiology↗

bioRxiv2019

Vglut2 expression in dopamine neurons contributes to post-lesional striatal reinnervation

In Parkinsons disease, the most vulnerable neurons are found in the ventral tier of the substantia nigra (SN), while the adjacent dopamine (DA) neurons of the ventral tegmental area (VTA) are mostly spared. Although a significant subset of adult VTA DA neurons expresses Vglut2, a vesicular glutamate transporter, and release glutamate as a second neurotransmitter in the striatum, only very few adult SN DA neurons have this capacity. Previous work has demonstrated that lesions created by neurotoxins such as MPTP and 6-hydroxydopamine (6-OHDA) can upregulate the expression of Vglut2 in surviving DA neurons. Currently, the molecular mechanisms explaining the plasticity of Vglut2 expression in DA neurons are unknown, as are the physiological consequences for DA neuron function and survival. Here we aimed to characterize the developmental expression pattern of Vglut2 in DA neurons and the role of this transporter in post-lesional plasticity in these neurons. Using an intersectional genetic lineage-mapping approach, based on Vglut2-Cre and TH-Flpo drivers, we first found that more than 98% of DA neurons expressed Vglut2 at some point in their embryonic development. Expression of this transporter was detectable in most DA neurons until E11.5 and was found to be localized in developing axons. Moderate enhancement of VGLUT2 expression in primary DA neurons caused an increase in axonal arborization length. Compatible with a developmental role, constitutive deletion of Vglut2 caused a regional defect in TH-innervation of the dorsal striatum in E18.5 embryos. Moreover, using an in vitro neurotoxin model, we demonstrate that Vglut2 expression can be upregulated in post-lesional DA neurons by 2.5-fold, arguing that the developmental expression of Vglut2 in DA neurons can be reactivated at postnatal stages and contribute to post-lesional plasticity of dopaminergic axons. In support of this hypothesis, we find fewer mesostriatial dopaminergic projections in the striatum of conditional Vglut2 KO mice 7 weeks after a neurotoxic lesion, compared to control animals. Thus, we propose here that one of the functions of Vglut2 in adult DA neurons is to promote post-lesional recovery of meso-striatal axons.

neuroscience↗