Biology subjects

Pichardo-Casas, I.

Publications and source records attributed to Pichardo-Casas, I..

3 recordsLinked to original sources

bioRxiv2026

Genome-resolved metagenomics of traditional fermented beverages reveals biosynthetic diversity and informs the rational in silico design of probiotic synthetic communities

Fermentation of foods and beverages represents one of humanitys oldest biotechnologies, generating compounds with demonstrated benefits for gut microbiota modulation, immune regulation, and metabolic health. The global rise of non-communicable chronic diseases, including obesity, type 2 diabetes, and chronic inflammation, has intensified the search for microbiome-based interventions, positioning fermented beverages as promising sources of next-generation probiotics and functional microbial consortia. Beverages such as kefir and kombucha, together with traditional Mexican fermented beverages including pozol and pulque, have been subjected to high-depth shotgun metagenomic studies generating high quality genomic resources. Systematic genomic mining efforts aimed at the functional characterization and biotechnological exploitation of these microbial communities, however, remain scarce. Here, we used a bioprospecting pipeline applied to milk-based kefir, kombucha, pozol, and pulque, integrating targeted genomic mining of genes associated with the biosynthesis of B-group vitamins, short-chain fatty acids, natural products, and CAZymes with potential to enhance starch and dietary fiber utilization upon intestinal colonization. Through genome-scale metabolic modeling of metagenome-assembled genomes, we identified microbial candidates predicted as central producers of secondary metabolites involved in pathogen control. We then used these results for the in silico synthetic assembly of a six-member synthetic microbial community predicted to exhibit stable cooperative growth and high metabolic functionality. Cross-feeding analysis revealed iron as one of the most widely shared elements among community members, with Priestia flexa from pozol, serving as a major donor of compounds involved in iron transport and as a stabilizing element within the synthetic community. This approach allows us to design a theoretical highly functional probiotic community, opening new avenues for the systematic exploitation of microbial diversity for biomedical purposes.

bioinformatics↗

bioRxiv2025

Mitochondrial Dysfunction Induces Hepatic Lipid Accumulation and Inflammatory Responses in mtDNA Mutator Mice

BackgroundNon-Alcoholic Fatty Liver Disease (NAFLD), now referred to as Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), is a widespread and complex health issue characterized by the accumulation of lipids in liver cells, not linked to alcohol consumption or other known liver problems. Despite its strong association with insulin resistance and obesity, a notable proportion of lean individuals develop NAFLD, suggesting the involvement of additional factors. Mitochondrial dysfunction has emerged as a potential contributor, given its role in lipid homeostasis and the generation of reactive oxidative species (ROS). MethodsIn this study, we took advantage of the mtDNA mutator mouse model, characterized by oxidative phosphorylation deficiency due to accelerated accumulation of mitochondrial DNA (mtDNA) mutations, to investigate how mitochondrial dysfunction affects liver homeostasis triggering fat accumulation. ResultsWe found that mitochondrial dysfunction induces liver steatosis and inflammation in this mouse model at a young age, independent of obesity. Using quantitative mass spectrometry, we reveal that mitochondrial dysfunction alters the levels of multiple proteins involved in lipid metabolism, cholesterol homeostasis, and inflammation. In vitro data show a shift in cellular metabolism toward the glycolytic pathway and confirm the upregulation of inflammatory genes. These changes are associated with oxidative stress and occur independently of mtDNA molecule release into the cytoplasm. ConclusionOur findings demonstrate that liver steatosis might develop as result of mitochondrial dysfunction without obesity and insulin resistance, underscoring the importance of mitochondrial dysfunction in NAFLD development in lean individuals and providing valuable insights into the molecular mechanisms underlying this complex metabolic disorder. This mouse model offers a unique platform for further investigations aimed at unraveling the intricacies of NAFLD pathogenesis and potential therapeutic targets beyond conventional risk factors.

cell biology↗

bioRxiv2020

Two neuronal peptides encoded from a single transcript regulate mitochondrial function in Drosophila

Naturally produced peptides (<100 amino acids) are important regulators of physiology, development, and metabolism. Recent studies have predicted that thousands of peptides may be translated from transcripts containing small open reading frames (smORFs). Here, we describe two peptides in Drosophila encoded by conserved smORFs, Sloth1 and Sloth2. These peptides are translated from the same bicistronic transcript and share sequence similarities, suggesting that they encode paralogs. Yet, Sloth1 and Sloth2 are not functionally redundant, and loss of either peptide causes animal lethality, reduced neuronal function, impaired mitochondrial function, and neurodegeneration. We provide evidence that Sloth1/2 are highly expressed in neurons, imported to mitochondria, and regulate mitochondrial complex III assembly. These results suggest that phenotypic analysis of smORF genes in Drosophila can provide a wealth of information on the biological functions of this poorly characterized class of genes.

genomics↗