Biology subjects

Romero, A. S.

Publications and source records attributed to Romero, A. S..

6 recordsLinked to original sources

bioRxiv2026

Photoaged microplastics disrupt endothelial stretch-sensitive ion channels to impair calcium signaling and vascular integrity

Plastic-derived micro- and nanoplastics are pervasive, but how environmentally aged particles affect vascular barriers is poorly understood. We hypothesized that photoaged plastics impair endothelial force-sensing, triggering gut-brain-heart barrier failure. Ultraviolet (UV) exposure converted pristine nanoplastics into oxidized, irregular photoaged microplastic aggregates (> 1.2 {micro}m). In human aortic endothelial cells, photoaged particles increased membrane stiffness and activated transcriptional programs linked to permeability, junction disruption, inflammation, and cytoskeletal remodeling. Mechanistically, photoaged particles selectively inhibited Piezo1-mediated Ca2+ signaling and downstream Notch activity without changing PIEZO1 expression, and endothelial CRISPR inhibition of PIEZO1 recapitulated these effects. In zebrafish, photoaged plastic exposure increased gut-vascular permeability and systemic spread with brain and heart accumulation, accompanied by reduced neurovascular and myocardial Ca2+ signals, depressed cardiac contractility, and abnormal locomotor behavior. Thus, photoaged plastics compromise vascular barriers through disrupted endothelial Piezo1-Notch mechanotransduction.

cell biology↗

bioRxiv2026

Dietary Microplastics Engage Gut Mechanosensory-Endocrine Signaling to Disrupt Bone Homeostasis

Background and AimsMicroplastics are pervasive environmental contaminants increasingly detected in food and water supplies; however, their effects on gastrointestinal physiology and systemic health remain poorly understood. We investigated whether chronic dietary microplastic exposure alters colonic neuroendocrine signaling and skeletal health. MethodsFemale and male C57BL/6J mice were fed purified basal, high-fat/high-cholesterol, or high-fiber diets with or without a physiological relevant polystyrene microplastic mixture ([~]1.7 mg/kg; particle sizes 0.49 - 5.0 {micro}m) for 12 weeks. Colonic cellular responses were evaluated using ELISA, histology, immunofluorescence, and single-nuclei RNA sequencing. Fecal microbiota transplantation was performed to assess microbial contributions to microplastic-induced phenotypes. Bone microarchitecture was assessed by micro-computed tomography. Human bone specimens were analyzed for microplastic content, and primary osteoblast mineralization assays were performed. ResultsDietary microplastic exposure increased chromogranin A-positive enteroendocrine cells and enhanced serotonergic signaling in the colon without evidence of intestinal inflammation or lineage reprogramming. Single-nuclei transcriptomic analysis identified compartment-specific serotonergic and mechanosensory adaptations in epithelial and enteric neuronal populations. Transfer of microbiota from microplastic-exposed donors to control recipients recapitulated increased enteroendocrine cell abundance. Chronic microplastic ingestion induced sex- and diet-dependent reductions in trabecular bone loss and architecture without systemic inflammatory activation. Microplastics were detected in human mineralized bone, and microplastic exposure impaired osteoblast mineralization in a donor-dependent manner. ConclusionsChronic ingestion of microplastics remodels gut neuroendocrine signaling through microbiota-dependent mechanisms and impairs skeletal homeostasis in the absence of overt inflammation. These findings identify a previously unrecognized gut-bone pathway through which dietary microplastic exposure may influence host physiology.

physiology↗

bioRxiv2025

Metabolomic, Lipidomic, and Enterohormone Changes in the Progression from MASLD to MASH

Background & AimsMetabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Metabolic Dysfunction-Associated Steatohepatitis (MASH) represent progressive stages of liver disease, with distinct metabolic and cellular alterations. This study investigates the progression from MASLD to MASH through metabolomics, lipidomics, and assessment of hormones. MethodsMale C57BL/6NTac mice were fed a high-fat diet for 16 weeks to induce MASLD and for 29 weeks to develop MASH. Aged-matched controls on a normal diet were used for comparison. Histology confirmed the progression of MASLD to MASH. We performed metabolomic and lipidomic profiling of liver, colon, and stool samples to identify metabolic and lipid alterations. Plasma enteroendocrine hormones and cytokines were quantified. Immunofluorescence was performed to assess enteroendocrine cells changes in the colon and the association of serotonin (5-HT) with fibronectin in the liver. ResultsMetabolomic and lipidomic analysis revealed significant alterations at different stages of the disease. Specifically, cholic acid was increased across the liver, colon, and stool in both MASLD and MASH mice compared to controls. Compared to the control group, MASLD mice exhibited an increase in enteroendocrine hormones, GLP-1, GIP, and PYY, whereas no changes were observed in MASH mice. Comparing MASLD to MASH livers, we found hepatic 5-HT levels were increased in MASH mice compared to MASLD mice. The MASH liver also exhibited a colocalization between fibronectin and 5-HT, suggesting a potential role of 5-HT in liver fibrosis. ConclusionsOur study provides novel insights into the progressive metabolic and hormonal changes from MASLD to MASH. The increase in cholic acid and differential enteroendocrine hormone responses highlight the complex interactions between the gut and liver in metabolic liver diseases. These findings suggest that enteroendocrine hormones may play a role in the progression of MASLD to MASH as well as liver fibrosis, offering potential therapeutic avenues for targeting the gut-liver axis in metabolic liver diseases.

cell biology↗

bioRxiv2025

In vivo exposure of mixed microplastic particles in mice and its impacts on the murine gut microbiome and metabolome

Microplastics (MPs) are emerging environmental contaminants due to increasing global plastic production and waste. Microplastics, defined as plastic particles less than 5 mm in diameter, are formed through degradation of larger plastics via sunlight, weathering, and microbes. These plastic compounds are widely detected in water, soil, food, as well as human stool and blood. The gut microbiome, often referred to as our second genome, is important in human health and is the primary point of contact for orally ingested microplastics. To investigate the impact of ingested MPs on the gut microbiome and the metabolome, 8 weeks-old male and female C57/BL6 mice were orally gavaged mixed plastic (5 um) exposure consisting of polystyrene, polyethylene, and the biodegradable/biocompatible plastic, poly-(lactic-co-glycolic acid) twice a week for 4 weeks at 0, 2, or 4 mg/week (n = 8/group). Fecal pellets were collected for bacterial DNA extraction and metagenomic shotgun sequencing, and serum was subjected to targeted and untargeted metabolomics. MPs exposure resulted in significant sex-specific and dose-dependent changes to the gut microbiome composition along with substantial regulation of the predicted metabolic pathways. Untargeted metabolomics in serum showed that a low MPs dose displayed a more prominent effect on key metabolic pathways such as amino acid metabolism, mitochondrial function, and inflammation. Additionally, SCFA-targeted metabolomics showed significant changes in neuroprotective SCFAs levels in both sexes by MPs exposure. In conclusion, our study has demonstrated that microplastics dysregulate the gut microbiome and serum metabolome, providing critical insights into potential human disease risks associated with microplastic contamination.

pharmacology and toxicology↗

bioRxiv2023

Inflammatory macrophages prevent colonic goblet and enteroendocrine cell differentiation through Notch signaling

Inflammatory macrophages in the intestine are a key pathogenic factor driving inflammatory bowel disease (IBD). Here, we report the role of inflammatory macrophage-mediated notch signaling on secretory lineage differentiation in the intestinal epithelium. Utilizing IL-10-deficient (Il10-/-) mice, a model of spontaneous colitis, we found an increase in Notch activity in the colonic epithelium as well as an increase in intestinal macrophages expressing Notch ligands, which are increased in macrophages upon inflammatory stimuli. Furthermore, a co-culture system of inflammatory macrophages and intestinal stem and proliferative cells during differentiation reduced goblet and enteroendocrine cells. This was recapitulated when utilizing a Notch agonist on human colonic organoids (colonoids). In summary, our findings indicate that inflammatory macrophages upregulate notch ligands that activate notch signaling in ISC via cell-cell interactions, which in turn inhibits secretory lineage differentiation in the gastrointestinal (GI) tract.

immunology↗

bioRxiv2023

In Vivo Tissue Distribution of Microplastics and Systemic Metabolomic Alterations After Gastrointestinal Exposure

Global plastic use has consistently increased over the past century with several different types of plastics now being produced. Much of these plastics end up in oceans or landfills leading to a substantial accumulation of plastics in the environment. Plastic debris slowly degrades into microplastics (MPs) that can ultimately be inhaled or ingested by both animals and humans. A growing body of evidence indicates that MPs can cross the gut barrier and enter into the lymphatic and systemic circulation leading to accumulation in tissues such as the lungs, liver, kidney, and brain. The impacts of mixed MPs exposure on tissue function through metabolism remains largely unexplored. To investigate the impact of ingested MPs on target metabolomic pathways, mice were subjected to either polystyrene microspheres or a mixed plastics (5 {micro}m) exposure consisting of polystyrene, polyethylene and the biodegradability and biocompatible plastic, poly-(lactic-co-glycolic acid). Exposures were performed twice a week for four weeks at a dose of either 0, 2, or 4 mg/week via oral gastric gavage. Our findings demonstrate that, in mice, ingested MPs can pass through the gut barrier, be translocated through the systemic circulation, and accumulate in distant tissues including the brain, liver, and kidney. Additionally, we report on the metabolomic changes that occur in the colon, liver and brain which show differential responses that are dependent on dose and type of MPs exposure. Lastly, our study provides proof of concept for identifying metabolomic alterations associated with MPs exposure and adds insight into the potential health risks that mixed MPs contamination may pose to humans.

pharmacology and toxicology↗