Biology subjects

Aparicio, C.

Publications and source records attributed to Aparicio, C..

4 recordsLinked to original sources

bioRxiv2026

Identification of specific gut bacteria and metabolomic signatures related to Myocardial Insulin Resistance in Type 2 Diabetes

BackgroundIn myocardial insulin resistance (mIR), insulin fails to appropriately stimulate myocardial glucose uptake, which can contribute to the development of heart disease. This reversible metabolic abnormality occurs in only a fraction of patients with type 2 diabetes mellitus (T2DM) and may be present even before clinical symptoms or the onset of diabetes. Identifying biomarkers of early-stage mIR is crucial to halt its progression with appropriate treatment and lifestyle interventions. In this context, we explore, for the first time, specific gut bacteria and fecal and plasma metabolic signatures associated with mIR. MethodsForty-two T2DM patients were divided into two groups, mIR patients patients with myocardial insulin sensitivity (mIS), depending on their myocardial glucose uptake measured with 18F-FDG PET during the hyperglycemic clamp. For each group, fecal microbiota was quantified by Illumina sequencing, and metabolomic profiles in feces and plasma were determined by NMR spectroscopy. ResultsThe Faiths phylogenetic diversity index was reduced significantly in mIR patients, compared with mIS patients. Linear discriminant analysis effect size (LEfSe) analysis revealed 25 bacterial taxa differing between mIS and mIR groups, and 6 bacteria (Thermicanus, Lachnobacterium, Desulfovibrio, Desulfuromusa, Desulfosporosinus and Coprobacillus cateniformis) were significantly decreased in mIR patients at the genus and species levels. Multivariate metabolomic analysis determined that six fecal metabolites (arabinose, {beta}-galactose and ribose, aspartate, histidine and lactate) and six plasma metabolites (creatinine, myo-inositol, threonine, {beta}-galactose, glycerol and choline) were reduced in mIR patients while plasmatic levels of VLDL(CH3) were elevated significantly. Myocardial IR correlated positively with plasmatic VLDL(CH3) and was negatively associated with two bacteria (Desulfosporosinus and Coprobacillus cateniformis), five fecal metabolites (arabinose, {beta}-galactose, ribose, aspartate, and histidine) and two plasma metabolites (choline and {beta}-galactose). ConclusionsOur pilot study proved that the gut microbiome and the metabolic plasma profile is altered in T2DM patients with mIR. Regression analysis and predictive modelling identified the bacteria Desulfosporosinus and the metabolite galactose as key biomarkers, which could aid in the identification of T2DM patients at risk for myocardial IR and in the design of novel therapeutic strategies to prevent it.

microbiology↗

bioRxiv2022

Functional Biomarkers of Ex-vivo Dental Caries Onset

BackgroundThe etiology of dental caries remains poorly understood. With the advent of next generation sequencing, a number of studies have focused on the microbial ecology of the disease. However, taxonomic associations with caries have not been consistent. Researchers have also pursued function-centric studies of the caries microbial communities aiming to identify consistently conserved functional pathways. A major question is whether changes in microbiome are a cause or a consequence of the disease. Thus, there is a critical need to define conserved functional biomarkers at the onset of dental caries. MethodsSince it is unethical to induce carious lesions clinically, we developed an innovative longitudinal ex-vivo model integrated with the advanced non-invasive multiphoton second harmonic generation bioimaging to spot the very early signs of dental caries, combined with 16S rRNA short amplicon sequencing and liquid chromatography-mass spectrometry-based targeted metabolomics. FindingsFor the first time, we induced longitudinally-monitored caries lesions validated with the scanning electron microscope. Consequently, we spotted the caries onset and, associated to it, distinguished five differentiating metabolites - Lactate, Pyruvate, Dihydroxyacetone phosphate, Glyceraldehyde 3-phosphate (upregulated) and Fumarate (downregulated). Those metabolites co-occurred with certain bacterial taxa; Streptococcus, Veillonella, Actinomyces, Porphyromonas, Fusobacterium, and Granulicatella, regardless of the abundance of other taxa. InterpretationThese findings are crucial for understanding the etiology and dynamics of dental caries, and devising targeted interventions to prevent disease progression. FundingThe study was funded by the National Institute for Dental and Craniofacial Research of the National Institutes of Health and the University of Minnesota. Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSStudies have shown that dental caries, tooth decay, occurs as a result of disruptive imbalance in the oral ecosystem. Excessive dietary intake of fermentable carbohydrates is a critical contributor to disease progression by promoting bacterial production of acids, which shifts the microbial community to an imbalanced and a less diverse one. Studies have also shown that microbial associations with caries have not been consistent while their functions are relatively conserved across individuals. Still, the specific microbial functions associated with the dental caries onset is still unknown due to its infeasible clinical diagnosis. Added value of this studyThis study applied a novel longitudinal ex-vivo model, integrated with advanced non-invasive bioimaging, for experimental dental caries induction. This model enabled the detection of the exact onset of the disease, which is undetected clinically. Then, the microbial communities accompanying the caries onset were analyzed for their microbial composition and metabolic functions in comparison to normal conditions. Our study identified five metabolites differentiating the caries onset. Further, we investigated the co-occurrence of these metabolic biomarkers with certain oral bacteria. Implications of all the available evidenceOur study provides carefully validated evidence for biomarkers of the dental caries onset. These data are critical for early diagnostics and development of timely intervention strategies to interfere with the disease progression that otherwise requires invasive and costly health care expenses. Moreover, our data open new avenues for developing therapeutics to neutralize the identified metabolic biomarkers or target the accountable bacteria for caries prevention.

microbiology↗

bioRxiv2020

COVID-19-associated olfactory dysfunction reveals SARS-CoV-2 neuroinvasion and persistence in the olfactory system

While recent investigations have revealed viral, inflammatory and vascular factors involved in SARS-CoV-2 lung pathogenesis, the pathophysiology of neurological disorders in COVID-19 remains poorly understood. Yet, olfactory and taste dysfunction are rather common in COVID-19, especially in pauci-symptomatic patients which constitutes the most frequent clinical manifestation of the infection. We conducted a virologic, molecular, and cellular study of the olfactory system from COVID-19 patients presenting acute loss of smell, and report evidence that the olfactory epithelium represents a highly significant infection site where multiple cell types, including olfactory sensory neurons, support cells and immune cells, are infected. Viral replication in the olfactory epithelium is associated with local inflammation. Furthermore, we show that SARS-CoV-2 induces acute anosmia and ageusia in golden Syrian hamsters, both lasting as long as the virus remains in the olfactory epithelium and the olfactory bulb. Finally, olfactory mucosa sampling in COVID-19 patients presenting with persistent loss of smell reveals the presence of virus transcripts and of SARS-CoV-2-infected cells, together with protracted inflammation. Viral persistence in the olfactory epithelium therefore provides a potential mechanism for prolonged or relapsing symptoms of COVID-19, such as loss of smell, which should be considered for optimal medical management and future therapeutic strategies.

neuroscience↗

bioRxiv2020

The parotid secretory protein BPIFA2 is a salivary surfactant that affects LPS action

Saliva plays important roles in the mastication, swallowing and digestion of food, speech and lubrication of oral mucosa, antimicrobial and anti-inflammatory activity and control of body temperature in grooming animals. The salivary protein BPIFA2 (BPI fold containing family A member 2; former names: Parotid Secretory Protein, PSP, SPLUNC2, C20orf70) is related to lipid-binding and LPS-binding proteins expressed in mucosa. Indeed, BPIFA2 binds LPS but the physiological role of BPIFA2 remains to be determined. To address this question, Bpifa2 knockout (Bpifa2tm1(KOMP)Vlcg) (KO) mice were phenotyped with a special emphasis on saliva and salivary glands. Saliva collected from KO mice was less able to spread on a hydrophobic surface than wild-type saliva and the surface tension of KO saliva was close to that of water. These data suggest that BPIFA2 is a salivary surfactant that is mainly responsible for the low surface tension of mouse saliva. The reduced surfactant activity of KO saliva did not affect consumption of dry food or grooming, but saliva from KO mice contained less LPS than wild-type saliva. Indeed, mice lacking BPIFA2 responded to ingested LPS with an increased stool frequency, suggesting that BPIFA2 plays a role in the solubilization and activity of ingested LPS. Consistent with these findings, BPIFA2-depleted mice also showed increased insulin secretion and metabolomic changes that were consistent with a mild endotoxemia. These results support the distal physiological function of a salivary protein and reinforce the connection between oral biology and systemic disease.

physiology↗