Biology subjects

Ambre, M.

Publications and source records attributed to Ambre, M..

4 recordsLinked to original sources

bioRxiv2026

Replication of Host St6galnac1-Microbiome Association Across Distinct Experimental Conditions in Heterogeneous Stock Rats

The gut microbiome is shaped by both environmental and host genetic factors. Identifying specific host loci is essential for understanding the heritability of microbiome-associated traits. The gene St6galnac1 encodes a sialyltransferase involved in mucin O-glycosylation. Tonnele et al. (2025) identified significant associations between a locus containing St6galnac1 gene, and the abundance of genus Paraprevotella using cecal samples collected from fasted animals. This association was replicated across three cohorts and paralleled with association found in humans between a functionally related sialyltransferase gene ST6GAL1 and Paraprevotella. Given the sensitivity of microbiome analyses to factors including sampling site, feeding status, and analytical framework, independent replication of these findings is important and it is also important to know if the association generalizes across other conditions or is highly specific to certain environments. Here, we performed a replication analysis using stool (not cecal) samples from 174 HS rats that were not fasted prior to collection. Stool samples underwent 16S rRNA gene sequencing, and microbial community structure was analyzed using compositionally aware methods. The rats were genotyped at the top SNP that was associated with Paraprevotella in the Tonnele et al. (2025) study. The association between genotype and Paraprevotella abundance was tested using a linear mixed model accounting for sex, cohort, and genetic relatedness. We successfully replicated (p=0.015) St6galnac1 - Paraprevotella association. These findings support the robustness of the St6galnac1 - Paraprevotella association across different sampling strategies and experimental conditions.

genomics↗

bioRxiv2026

Genome-resolved ecology and evolution of the microbiome enabled by quantitative long-read metagenomics

Standard metagenomics resolves microbial communities only in relative terms and at coarse taxonomic resolution, obscuring how individual strains change in absolute abundance and evolve within a host. We present long-read quantiomics (LRQ), a quantitative metagenomics platform coupling long-read sequencing with plasmid-based internal standards to recover high-quality genomes, including from degraded or low-input stool, and measure absolute, genome-resolved strain abundances. We validate LRQ using large plasmid standards and bacterial spike-ins, then apply it to eight years of dense sampling from an individual with colonic Crohn's disease. LRQ resolves co-resident strains of the same species following opposing trajectories with inflammation. Escherichia coli, long treated as a single pathobiont, separates into two sub-populations with opposing inflammation responses; the inflammation-associated lineage carries an immune-evasion module of virulence-associated metal-acquisition, biofilm, capsule and toxin genes. We observe genome-wide adaptive sweeps on timescales matched to disease incidence. LRQ therefore converts long-read metagenomics from a genome-recovery tool into a quantitative framework providing absolute, strain-level measurement of microbial ecology and evolution.

microbiology↗

bioRxiv2026

Farnesoid X receptor-dependent microbiome-bile acid signaling mediates obstructive sleep apnea-induced atherosclerosis

Intermittent hypoxia and hypercapnia (IHC), a hallmark of obstructive sleep apnea (OSA), accelerates atherosclerosis, yet the underlying mechanisms remain unclear. The gut microbiota and metabolites, specifically bile acids, change with IHC and thus the bile acid receptor farnesoid X receptor (FXR) might mediate IHC-induced atherosclerosis. In this study, ApoE-/- and ApoE-/- FXR-/- mice were exposed to IHC or room air and fed with a high-fat, high-cholesterol diet for 10 weeks. Markers of atherosclerosis, fecal microbiome, and metabolome were then examined via Sudan IV staining, absolute abundance shotgun metagenomics, and untargeted liquid chromatography tandem mass spectrometry (LC-MS/MS). IHC markedly increased aortic atherosclerosis in ApoE-/-mice, an increase that was abolished by FXR deficiency. In addition, IHC reshaped gut microbial composition, promoting enrichment of bile acid-modifying taxa and increasing levels of microbial hydroxysteroid dehydrogenase (hsdh). The bile acid pool was also remodeled and associated with aortic atherosclerosis via FXR-dependent metabolic signals in ApoE-/- mice. Knockout of FXR disrupted microbiome shift under IHC and uncoupled microbial bile acid metabolism from vascular lesion development, thereby protecting against aortic atherosclerosis. These findings show that FXR has a central role in linking IHC, microbial bile acid metabolism, and cardiovascular pathology.

microbiology↗

bioRxiv2024

Empirically establishing drug exposure records directly from untargeted metabolomics data

Despite extensive efforts, extracting information on medication exposure from clinical records remains challenging. To complement this approach, we developed the tandem mass spectrometry (MS/MS) based GNPS Drug Library. This resource integrates MS/MS data for drugs and their metabolites/analogs with controlled vocabularies on exposure sources, pharmacologic classes, therapeutic indications, and mechanisms of action. It enables direct analysis of drug exposure and metabolism from untargeted metabolomics data independent of clinical records. Our library facilitates stratification of individuals in clinical studies based on the empirically detected medications, exemplified by drug-dependent microbiota-derived N-acyl lipid changes in a cohort with human immunodeficiency virus. The GNPS Drug Library holds potential for broader applications in drug discovery and precision medicine.

bioinformatics↗