Biology subjects

Rabot, S.

Publications and source records attributed to Rabot, S..

3 recordsLinked to original sources

bioRxiv2026

Multi-omic dissection of reversible and persistent molecular alterations in diet-induced obesity

Diet-induced obesity drives broad molecular remodeling across host and microbial systems, but why lifestyle intervention reverses some of these alterations while others persist remains unclear. To address this, we performed a multi-omic characterization of diet-induced obese mice after a combined nutritional and exercise intervention, integrating liver transcriptomics, epigenomics, metabolomics and metallomics with gut metagenomics and metallomics. Multi-omics factor analysis resolved two dominant axes of variation. The first captured a broadly reversible response (~72% of altered variables), restored by dietary restriction and exercise, involving coordinated remodeling of hepatic metal homeostasis, epigenetic regulation, and immune and cell-turnover pathways. The second comprised persistent alterations resistant to intervention and driven primarily by microbial functional profiles: notably, functional diversity remained reduced despite substantial taxonomic recovery. Using germ-free mice to define the microbiota-responsive hepatic space, we found that a significant fraction of the persistent liver features fell within it, enriched in lipid metabolism (PPAR signaling, steroid and cholesterol biosynthesis, peroxisomal activity) and retinol metabolism. Sequential correlation analysis traced these changes to the loss of specific low-abundance taxa and their biosynthetic capacities, particularly vitamin (folate, biotin, cobalamin, pantothenate, thiamine) and cofactor metabolism, implicating microbiota-derived vitamin metabolism in sustained hepatic dysfunction. Cobalt was the sole essential element that remained persistently dysregulated and tracked dietary cobalt content, suggesting a diet--microbiota route to the persistent phenotype. These findings establish a dual regulatory framework in which metabolic plasticity is governed by reversible host-intrinsic and persistent microbiota-dependent processes, providing a systems-level explanation for obesogenic memory.

systems biology↗

bioRxiv2023

A targeted metabolomic method to detect epigenetically relevant metabolites

Metabolites play a central role in the chemical crosstalk between metabolism and epigenetic marks. Epigenetically relevant metabolites are substrates, products and cofactors that can act as activators or inhibitors of epigenetic enzymes, which control gene expression by adding or removing chemical marks in the DNA, RNA and histones. Diet composition, and biosynthetic pathways encoded in the gut microbiome and the host genome are the main sources of these metabolites for mammals. Despite the increasing interest in the study of the microbiota-nutrient metabolism-host epigenetic axis to understand health and disease, there is a lack of a sensitive and easy analytical method to detect epigenetically relevant metabolites simultaneously. Here, we show an straightforward biphasic extraction where the organic phase is directly analyzed by GC-EI MS to detect short-chain fatty acids and formate without chemical derivatization, and the aqueous phase is analyzed by HILIC coupled to ESI-MS/MS, which together can cover >30 epigenetically relevant metabolites in biological samples such as liver, plasma or feces. In addition, we propose a stable isotope tracing method based on multiple-reaction monitoring (MRM) transitions by LC-QqQ MS to understand how 13C-labeled glucose or glutamine are used to build SAM and acetyl-CoA, the main methyl and acetyl group donors in epigenetic modifications, respectively. We anticipate that our methods will complement epigenomic and proteomic analyses adding another layer of molecular information towards mechanistic insights. HighlightsO_LIHost and microbiota metabolites link metabolism with epigenetic regulation. C_LIO_LIChemical structure diversity in epigenetically relevant metabolites challenges its analysis with a single method. C_LIO_LIA biphasic extraction with no chemical derivatization is able to recover SCFAs and other epigenetically relevant metabolites. C_LIO_LIA novel isotope trace experiment approach allows isotopomer resolution using MS2 data. C_LI

biochemistry↗

bioRxiv2021

Microbiota and stress: a loop that impacts memory

Chronic stress and the gut microbiota appear to comprise a feed-forward loop, which contributes to the development of depressive disorders. Evidence suggests that memory can also be impaired by either chronic stress or microbiota imbalance. However, it remains to be established whether these could be a part of an integrated loop model and be responsible for memory impairments. To shed light on this, we used a two-pronged approach in Japanese quail: first stress-induced alterations in gut microbiota were characterized, then we tested whether this altered microbiota could affect brain and memory function when transferred to a germ-free host. The cecal microbiota of chronically stressed quails was found to be significantly different from that of unstressed individuals with lower and {beta} diversities and increased Bacteroidetes abundance largely represented by the Alistipes genus, a well-known stress target in rodents and humans. The transfer of this altered microbiota into germ-free quails decreased their spatial and cue-based memory abilities as previously demonstrated in the stressed donors. The recipients also displayed increased anxiety-like behavior, reduced basal plasma corticosterone levels and differential gene expression in the brain. Furthermore, cecal microbiota transfer from a chronically stressed individual was sufficient to mimic the adverse impact of chronic stress on memory in recipient hosts and this action may be related to the Alistipes genus. Our results provide evidence of a feed-forward loop system linking the microbiota-gut-brain axis to stress and memory function and suggest that maintaining a healthy microbiota could help alleviate memory impairments linked to chronic stress.

animal behavior and cognition↗