Biology subjects

Blottiere, H. M.

Publications and source records attributed to Blottiere, H. M..

4 recordsLinked to original sources

bioRxiv2026

Grey mouse lemurs, Microcebus murinus, are a relevant model to study gut microbiome flexibility in response to diet changes

The gut microbiota is a key player in energy balance, impacting both digestion efficiency and the production of metabolites involved in metabolism. Its composition is highly adaptable, especially in response to diet. Changes in human diet and lifestyle over time - from active, fibre-rich diets to sedentary habits with calorie-dense foods - have likely contributed to the rise in metabolic diseases. Rodent models are widely used to study the links between diet, microbiota and metabolism. However, they have important limitations (e.g. artificial environments, uniform diets and biological differences from humans) which can affect the translation of findings to humans. While mice and humans differ in their microbiota species, they do share some functional similarities. The grey mouse lemur (Microcebus murinus) has been proposed as a promising alternative model. This small primate experiences strong seasonal changes in food availability, leading to distinct physiological states (energy-saving in winter vs active in summer), even in captivity. It is increasingly recognized as a valuable model for biomedical research, supported by recent genomic and molecular advances. However, its gut microbiota has not yet been the subject of study. Consequently, the present study focuses on investigating the gut microbiota of the grey mouse lemur, with a particular emphasis on how these microbiota vary under different dietary regimens. The microbiota of animals fed the standard colony diet was dominated by Prevotella, Bifidobacterium, Megamonas, Streptococcus, Megasphaera and Lactococcus, showing an Prevotella driven enterosignature. We showed that switch from a classical control diet to 3 different diets resulted in change on microbiota composition that is associated with functional redundancy. The present work underline the interest of Microcebus murinus as model for diet and lifestyle studies in relationship with metabolic diseases.

microbiology↗

bioRxiv2026

Dissociated responses of vesiculogenesis and amoxicillin impact on extracellular vesicle production of first gut bacterial colonizers Bifidobacterium longum and Lactiplantibacillus plantarum

Bacterial extracellular vesicles (bEVs) have emerged as important mediators of microbiota-host interplay through the transport of active biomolecules, namely cargos, far from their release location. The neonatal period represents a critical window for the establishment of the gut microbiota and subsequent sustainable symbiotic communication. The gut primo-colonizing bacteria, including bifidobacteria and lactobacilli, likely contribute to the impact on the digestive, immune and neuron system maturation. However, exposures and experiences during this early stage may influence the development of health and diseases later on in life by altering these primo-interactions. As antibiotherapies are frequent in the postnatal period and associated to microbiota disorders, we evaluated the impact of amoxicillin on first colonizing Gram positive-derived EVs, using a robust and reproductible in-house workflow for the extraction and purification bEVs from Bifidobacterium longum and Lactiplantibacillus plantarum. The EVs production and the proteovesiculome profiles under amoxicillin treatment were compared. The results pointed out a dissociated response in the EVs release process and their regulation by amoxicillin according to strain with an enhance production of EVs for B. longum under amoxicillin. In addition, the proteovesicular analyses indicate that the vesicular protein profile was enriched and more diverse in B. longum-derived EVs from amoxicillin-treated cells than those from non-treated cells while the content shift in L. plantarum-derived EVs in amoxicillin-treated cells was in favor of protein richness loss. Overall, this study opens new avenues considering the impact of antibiotic therapies in the neonatal period on EVs derived from benefit Gram-positive gut bacteria.

microbiology↗

bioRxiv2025

CDKN1A (p21Cip/Waf1) stabilizes Cyclin D3 by inhibiting its phosphorylation-dependent nuclear export following butyrate treatment

Butyrate-mediated inhibition of cell proliferation is part of the preventive role of dietary fiber against colorectal cancer (CRC). This effect notably involves the cyclin-dependent kinase inhibitor CDKN1A (p21Cip/Waf1) in human intestinal cells, yet the underlying molecular mechanisms remain incompletely understood. Previously, we observed a paradoxical increase in cyclin D3 (CCND3)--but not cyclin D1--levels upon butyrate exposure. Here, we demonstrate that the butyrate-induced accumulation of CCND3 protein results both from mRNA increase and a CDKN1A-dependent protein stabilization, specifically extending its nuclear half-life. Proteomic analyses of CCND3 co-immunoprecipitates identified complexes involving CDKN1A, CDK4, CDK6, and the CRC-associated kinase CDK5, particularly enriched in butyrate-treated cells. Phosphorylation at a conserved Thr residue, crucial for CCND nuclear export and subsequent proteasomal degradation, was notably reduced following butyrate treatment and inversely correlated with CDKN1A expression levels. Structural modeling based on AlphaFold2, complemented by molecular dynamics simulations, revealed possible differential interactions between CDKN1A and cyclins D1 and D3, predicting that CCND3-Thr283 becomes structurally buried upon CDKN1A binding, limiting its phosphorylation. Our findings provide novel mechanistic insights into how CDKN1A might regulate CCND3 stability, highlighting previously unexplored roles of cyclin D3-containing complexes in cell cycle arrest induced by butyrate.

cell biology↗

bioRxiv2023

α-synuclein expression in response to bacterial ligands and metabolites in gut enteroendocrine cells

BackgroundCaudo-rostral migration of pathological forms of -synuclein from the gut to the brain is proposed as an early feature in Parkinson disease (PD) pathogenesis, but the underlying mechanisms remain unknown. Intestinal enteroendocrine cells sense and respond to numerous luminal signals, including bacterial factors, and transmit this information to the brain via the enteric nervous system and vagus nerve. There is evidence that gut bacteria composition and their metabolites change in PD patients and these alterations can trigger -synuclein pathology in animal models. ObjectiveHere we investigated the effect of toll-like receptor (TLR) and free fatty acid receptor (FFA2/3) agonists on -synuclein levels in mouse STC-1 enteroendocrine cells. MethodsSTC-1 cells were treated with TLR and FFA2/3 agonists alone and in combination with selective antagonists. The level of -synuclein protein was measured in cell lysates and cell culture media by western blot and ELISA. And the level of -synuclein and tumour necrosis factor (TNF) mRNA was measured by quantitative RT-PCR. ResultsTLR and FFA receptor agonists significantly increased intracellular and extracellular -synuclein levels and antagonists significantly reduced these effects. TLR and FFA receptor agonists also significantly increased TNF transcription and this was inhibited by corresponding antagonists. ConclusionsElevated intracellular -synuclein increases the likelihood of aggregation and conversion to toxic forms. Factors derived from bacteria induce -synuclein accumulation in STC-1 cells. Here we provide support for a mechanism by which exposure of enteroendocrine cells to specific bacterial factors found in PD gut dysbiosis might facilitate accumulation and transmission of -synuclein pathology from the gut to the brain.

neuroscience↗