Reytor González, Claudia
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Reytor González, Claudia
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Ambato

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Single vs. Dual Agonist Pharmacotherapy for Managing Insufficient Weight Loss and Weight Regain Following Metabolic and Bariatric Surgery: A Comparative Review

2026 , Reytor González, Claudia , Martín Campuzano-Donoso , Gerardo Sarno , Martha Montalvan , Raquel Horowitz , Gianluca Rossetti , Vincenzo Pilone , Luigi Barrea , Giovanna Muscogiuri , Luigi Schiavo , Simancas Racines, Daniel

Weight management after metabolic and bariatric surgery remains a persistent clinical challenge, particularly when patients experience insufficient weight loss or progressive weight regain following the postoperative nadir. In recent years, pharmacological therapies targeting gut-derived hormones have reshaped the therapeutic approach, offering nonsurgical strategies that directly influence appetite regulation, satiety, and energy balance. Single agonists acting on the glucagon-like peptide one receptor have demonstrated meaningful reductions in body weight among postoperative patients, while dual agonists that target both the glucagon-like peptide one receptor and the glucose-dependent insulinotropic polypeptide receptor have shown even greater weight reduction in early studies, suggesting enhanced therapeutic potential. These benefits, however, must be interpreted within the unique anatomical, nutritional, and behavioral context of individuals who have undergone metabolic and bariatric procedures, as they are inherently at higher risk for micronutrient deficiencies, gastrointestinal intolerance, and maladaptive eating patterns. Successful treatment requires a balanced integration of pharmacotherapy, individualized nutritional guidance, psychological support, and a patient-centered model of long-term care. Although emerging evidence is promising, dedicated clinical trials are still needed to directly compare the efficacy, safety, and sustainability of single versus dual agonist therapies in postoperative populations. Furthermore, culturally sensitive dietary strategies and shared decision-making processes are essential to enhance adherence, optimize long-term outcomes, and ensure equitable access to treatment. Ultimately, these therapies represent a significant advance in addressing postoperative weight challenges, but their full potential will rely on comprehensive, multidisciplinary frameworks that support both biological and behavioral aspects of chronic weight management.

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Traditional Foods, Oral Microbiome, and Systemic Health: Molecular Pathways Linking Nutrition and Oral Disease Prevention

2026 , Parise Vasco, Juan Marcos , Angamarca Iguago, Jaime , Cagua Ordoñez, Jaen , Beatriz Cabrera , Dolores Jima Gavilanes , Raquel Horowitz , Reytor González, Claudia , Simancas Racines, Daniel

Periodontal disease affects 10–50% of the global population and is associated with various systemic conditions, including diabetes, cardiovascular disease and adverse pregnancy outcomes. Emerging evidence highlights diet as a critical, modifiable factor that influences the composition of the oral microbiome and periodontal health. This narrative review explores the molecular mechanisms through which traditional foods modulate the oral microbiome and contribute to oral and systemic health. A comprehensive literature search was conducted in PubMed/MEDLINE, the Cochrane Library, LILACS and Epistemonikos, prioritizing systematic reviews, meta-analyses and randomized controlled trials. The oral microbiome harbors over 700 bacterial species, and dysbiosis, characterized by pathogen enrichment, drives periodontal inflammation. Anti-inflammatory dietary patterns, including the Mediterranean diet, demonstrate protective effects. Omega-3 fatty acids, vitamins C and D, polyphenols and dietary fiber support periodontal health, whereas refined carbohydrates, saturated fats and pro-inflammatory nutrients can exacerbate disease. Probiotics show promise as an adjunctive therapy. However, the translation to clinical guidelines is impeded by methodological challenges, including the limited number of randomized controlled trials with oral endpoints, confounding by hygiene practices, and the lack of standardized multi-omics approaches. Nutritional counselling should be integrated into periodontal care as a modifiable risk factor. Future research priorities include precision nutrition approaches, the validation of salivary biomarkers, and interprofessional collaboration between dental and nutrition professionals. © 2026 by the authors.

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The Oral–Gut–Immune–Nutrition Axis in Rheumatoid Arthritis: Molecular Mechanisms and Therapeutic Implications

2026 , Reytor González, Claudia , Náthaly Mercedes Román-Galeano , Lenin Saul Aules-Curicama , Camila Doménica Cevallos-Villacis , Erik González , Dolores Jima Gavilanes , Raquel Horowitz , Simancas Racines, Daniel

Rheumatoid arthritis is a chronic systemic autoimmune disease that arises from complex interactions among genetic susceptibility, environmental factors, and immune dysregulation. Growing evidence indicates that microorganisms residing in the oral cavity and gastrointestinal tract, together with dietary factors, play a central role in shaping inflammatory and autoimmune responses in rheumatoid arthritis, forming an interconnected microbiome–immune–nutrition axis. Alterations in the composition and function of oral and intestinal microbial communities are associated with disruption of mucosal barrier integrity, activation of innate and adaptive immune pathways, increased differentiation of proinflammatory T lymphocyte subsets, and loss of immune tolerance that promotes autoantibody production. In addition, microbially derived metabolites, particularly short-chain fatty acids, provide a mechanistic link between microbial ecology, immune regulation, and bone metabolism. Diet represents a key upstream modulator of this axis. Dietary patterns rich in anti-inflammatory nutrients support microbial diversity and immunoregulatory metabolite production, whereas diets high in processed foods and saturated fats favor proinflammatory microbial profiles. Accumulating clinical evidence suggests that nutritional strategies and microbiome-targeted dietary interventions may reduce systemic inflammation and disease-related comorbidities when used alongside standard pharmacological treatments. Taken together, the microbiome–immune–nutrition axis represents a modifiable and clinically meaningful target in rheumatoid arthritis, emphasizing the need for interdisciplinary research and well-designed clinical trials to translate these insights into personalized approaches for disease management. The aim of this review is to integrate current mechanistic and clinical evidence on the interactions between the microbiome, immune system, and nutrition in rheumatoid arthritis, with a focus on their pathogenic relevance, therapeutic potential, and implications for personalized, diet-based interventions.

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Endometriosis as a Systemic and Complex Disease: Toward Phenotype-Based Classification and Personalized Therapy

2026 , Simancas Racines, Daniel , Emilia Jiménez-Flores , Martha Montalvan , Raquel Horowitz , Valeria Araujo , Reytor González, Claudia

Endometriosis is traditionally conceptualized as a pelvic lesion–centered disease; however, mounting evidence indicates it is a chronic, systemic, and multifactorial inflammatory disorder. This review examines the molecular dialog between ectopic endometrial tissue, the immune system, and peripheral organs, highlighting mechanisms that underlie disease chronicity, symptom variability, and therapeutic resistance. Ectopic endometrium exhibits distinct transcriptomic and epigenetic signatures, disrupted hormonal signaling, and a pro-inflammatory microenvironment characterized by inflammatory mediators, prostaglandins, and matrix metalloproteinases. Immune-endometrial crosstalk fosters immune evasion through altered cytokine profiles, extracellular vesicles, immune checkpoint molecules, and immunomodulatory microRNAs, enabling lesion persistence. Beyond the pelvis, systemic low-grade inflammation, circulating cytokines, and microRNAs reflect a molecular spillover that contributes to chronic pain, fatigue, hypothalamic–pituitary–adrenal axis dysregulation, and emerging gut–endometrium interactions. Furthermore, circulating biomarkers—including microRNAs, lncRNAs, extracellular vesicles, and proteomic signatures—offer potential for early diagnosis, patient stratification, and monitoring of therapeutic responses. Conventional hormonal therapies demonstrate limited efficacy, whereas novel molecular targets and delivery systems, including angiogenesis inhibitors, immune modulators, epigenetic regulators, and nanotherapeutics, show promise for precision intervention. A systems medicine framework, integrating multi-omics analyses and network-based approaches, supports reconceptualizing endometriosis as a systemic inflammatory condition with gynecologic manifestations. This perspective emphasizes the need for interdisciplinary collaboration to advance diagnostics, therapeutics, and individualized patient care, ultimately moving beyond a lesion-centered paradigm toward a molecularly informed, holistic understanding of endometriosis.

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