Biology subjects

Bou Sleiman, M. S.

Publications and source records attributed to Bou Sleiman, M. S..

3 recordsLinked to original sources

bioRxiv2023

Genetic and dietary modulators of the inflammatory response in the gastro-intestinal tract of the BXD mouse genetic reference population

Inflammatory gut disorders, including inflammatory bowel disease (IBD), can be impacted by dietary, environmental and genetic factors. While the incidence of IBD is increasing worldwide, we still lack a complete understanding of the gene-by-environment interactions underlying inflammation and IBD. Here, we profiled the colon transcriptome of 52 BXD mouse strains fed with a chow or high-fat diet (HFD) and identified a subset of BXD strains that exhibit an IBD-like transcriptome signature on HFD, indicating that an interplay of genetics and diet can significantly affect intestinal inflammation. Using gene co-expression analyses, we identified modules that are enriched for IBD-dysregulated genes and found that these IBD-related modules share cis-regulatory elements that are responsive to the STAT2, SMAD3, and REL transcription factors. We used module quantitative trait locus (ModQTL) analyses to identify genetic loci associated with the expression of these modules. Through a prioritization scheme involving systems genetics in the mouse and integration with external human datasets, we identified Muc4 and Epha6 as the top candidates mediating differences in HFD-driven intestinal inflammation. This work provides insights into the contribution of genetics and diet to IBD risk and identifies two candidate genes, MUC4 and EPHA6, that may mediate IBD susceptibility in humans.

systems biology↗

bioRxiv2021

Genetic, metabolic, and molecular insights into the diverse outcomes of diet-induced obesity in mice

Overweight and obesity are increasingly common public health issues worldwide, leading to a wide range of diseases from metabolic syndrome to steatohepatitis and cardiovascular diseases. While the increase in the prevalence of obesity is partly attributable to changes in lifestyle (i.e. increased sedentarity and changes in eating behaviour), the metabolic and clinical impacts of these obesogenic conditions varies between sexes and genetic backgrounds. The conception of personalised treatments of obesity and its complications require a thorough understanding of the diversity of responses to conditions such as high-fat diet intake. By analysing nine genetically diverse mouse strains, we show that much like humans, mice respond to high-fat diet in a genetic- and sex-dependent manner. Physiological and molecular responses to high-fat diet are associated with expression of genes involved in immunity and mitochondrial function. Finally, we find that mitochondrial function may explain part of the diversity of physiological responses. By exploring the complex interactions between genetics and metabolic phenotypes via gene expression and molecular traits, we shed light on the importance of genetic background and sex in determining metabolic outcomes. In addition to providing the community with an extensive resource for optimizing future experiments, our work serves as an exemplary design for more generalizable translational studies.

bioinformatics↗

bioRxiv2021

Multi-omics analysis identifies essential regulators of mitochondrial stress response in two wild-type C. elegans strains

The mitochondrial unfolded protein response (UPRmt) is a promising pharmacological target for aging and age-related diseases. However, the integrative analysis of the impact of UPRmt activation on different layers of signaling in animals with a different genetic background is lacking. In this study, we applied systems approaches to investigate the effect of UPRmt induced by administering doxycycline (Dox) on transcriptome, proteome, lipidome, and metabolome in two genetically divergent C. elegans strains. We found that Dox prolongs lifespan of both worm strains through pathways in both shared and strain-specific manners. From the integrated omics datasets, we observed a strong impact of Dox on mitochondrial functions, detected upregulated defense response and lipid metabolism, identified decreased triglycerides and lowered metabolome profiles in both strains. This conserved phenomic footprint has great translational value as it indicates that the beneficial effects of Dox-induced UPRmt on health and lifespan are consistent across different genetic backgrounds.

systems biology↗