Biology subjects

Vazquez-Prada, M.

Publications and source records attributed to Vazquez-Prada, M..

3 recordsLinked to original sources

bioRxiv2026

A defined microbial community remodels host metabolism and pathogen resistance in Caenorhabditis elegans

The microbiome is an important regulator of metabolism and health, yet the mechanisms by which microbial communities influence host physiological state remain incompletely understood. Here we used a defined host-microbiota model consisting of Caenorhabditis elegans and an 11-member bacterial consortium representative of its natural microbiota (DefNatMta). We investigated how this native microbial community influences host metabolism and physiology relative to the standard laboratory diet, E. coli OP50. Transcriptomic analyses revealed remodelling of host pathways associated with lipid metabolism, immunity and xenobiotic detoxification. Comparison with fasting-responsive transcriptional programmes showed that the DefNatMta response is distinct from fasting or caloric restriction. DefNatMta enhanced resistance to Staphylococcus aureus infection, and this protective effect was consistent with roles for the conserved host defence regulators PMK-1/p38 MAPK and HLH-30/TFEB. Additionally, DefNatMta reduced lipid accumulation, modified expression of lipid metabolism genes, and altered fatty acid composition, including enrichment of monomethyl branched-chain fatty acids and polyunsaturated fatty acids. Together, these findings demonstrate that a defined microbial community can induce transcriptional, metabolic and physiological remodelling in the host. Our results are consistent with microbial communities shaping host metabolic state and immune competence.

physiology↗

bioRxiv2025

FGF and MafB regulated cadherin expression drives lamina formation in the auditory hindbrain

The avian auditory brainstem contains specialized nuclei critical for sound localization, including the nucleus laminaris (nL), which forms as a single-cell-thick lamina essential for computing interaural time differences. Despite its functional importance, the molecular mechanisms guiding nL lamina formation have remained poorly understood. Here, we identify a signalling cascade involving FGF8, MafB, and cadherin-22 that orchestrates this morphogenetic process. We show that FGF8 is selectively expressed in the developing auditory hindbrain and correlates spatiotemporally with lamina formation in the nL. Disruption of FGF signalling--either via misexpression of FGF8 or dominant-negative FGFR1--perturbs the formation of the nL and alters cadherin-22 expression. In vitro culture experiments further reveal that nL lamination is sensitive to FGF8 dosage, with an optimal concentration required for both FGF8 and MafB expression and correct structural organization. We demonstrate that FGF8 induces MafB, which in turn regulates cadherin-22 expression. Functional disruption of cadherins impairs lamina formation and leads to reduced FGF8 expression, indicating a feedback loop between adhesion and signalling. Cadherin protein expression appears enriched in the dendrites of nL neurons and computational models--both static and dynamic--show that bipolar, dendrite-localized, adhesion can drive laminar architecture as the maximum adhesion configuration. These findings establish a novel molecular and biophysical mechanism for neuronal lamination in the vertebrate hindbrain, showing how local FGF signalling, transcriptional regulation, and dendritic adhesion converge to shape neural circuitry essential for sound localization.

developmental biology↗

bioRxiv2024

A gut-microbiota-muscle axis that protects against age-related motor decline by regulating mitochondrial fission in C. elegans

Across diverse taxa, the composition of the microbiota is associated with lifelong host health. A mechanistic understanding of how microbial communities influence host physiology could lead to microbiota-based interventions for lifelong health. Here, we have developed a new host-microbiota model system utilising the model organism C. elegans combined with a defined natural microbiota (DefNatMta) consisting of 11 bacteria isolated from wild C. elegans, to study host-microbiota interactions in a more natural setting. We show that DefNatMta colonises the C. elegans gut, forming a stable and distinct gut microbiota. Using DefNatMta, we find a gut microbiota-muscle axis by which the microbiota affects age-related motility and muscular strength and protects against age-related decline in motor function. The gut microbiota-muscle axis acts by altering metabolism and mitochondrial network dynamics in muscle, and requires dynamin-related protein 1 DRP-1, a regulator of mitochondrial fission to protect against age-related motility decline. Our study demonstrates a gut microbiota-muscle axis and microbiota-mitochondria communication affecting age-related muscle function.

physiology↗