학술논문
Gut Microbiota Signatures Associated with Weight Loss and Insulin Resistance in an Elderly Mediterranean Population with Overweight/Obesity and Metabolic Syndrome
Document Type
Dissertation/Thesis
Author
Source
TDX (Tesis Doctorals en Xarxa)
Subject
Language
English
Abstract
Las alteraciones en la composición y la funcionalidad de la microbiota intestinal pueden contribuir al desarrollo de la obesidad y la resistencia a la insulina. La identificación de específicas bacterias intestinales y de vías metabólicas asociadas a la obesidad y a los trastornos metabólicos relacionados, representa una perspectiva novedosa y prometedora para adaptar las intervenciones personalizadas. Los principales objetivos de esta tesis doctoral, diseñada en el marco del ensayo clínico PREDIMED (PREvención con DIeta MEDiterránea)-Plus, son: (i) Explorar la asociación entre la microbiota fecal, el índice de masa corporal y los cambios en el peso corporal total tras una intervención de 12 meses sobre el estilo de vida en sujetos de edad avanzada (entre 55 y 75 años) con sobrepeso/obesidad y síndrome metabólico; (ii) explorar la asociación entre la microbiota fecal y la resistencia a la insulina, estimada mediante el índice HOMA-IR, en sujetos no diabéticos de la misma cohorte. Los resultados mostraron géneros específicos de la microbiota fecal asociados con un menor índice de masa corporal y una mayor pérdida de peso a los 12 meses de seguimiento. Algunos géneros en concreto y las vías metabólicas relacionadas se asociaron negativamente con un mayor índice HOMA-IR y se vincularon con una mejor homeostasis de la glucosa a través de una mayor descomposición de aminoácidos y reducción de sulfatos. Además, otros géneros específicos y las vías metabólicas relacionadas se asociaron positivamente con el índice HOMA-IR y se relacionaron con una mayor degradación de los sacáridos que induce una producción anormal de butirato. Estos resultados apoyan la identificación de taxones específicos de la microbiota intestinal para predecir el éxito de los tratamientos contra la obesidad, pero también para seleccionar posibles candidatos bacterianos para el desarrollo de terapias contra la resistencia a la insulina. Estos resultados animan a seguir investigando, especialmente en lo que se refiere a la profundización de la exploración taxonómica y la elaboración de perfiles metabolómicos.
Alterations in gut microbial composition and functionality may contribute to the development of obesity and insulin resistance. The identification of specific gut bacteria and metabolic pathways associated with obesity and related metabolic disorders represents a promising novel perspective to tailor personalized interventions. The main objectives of this doctoral thesis, designed within the frame of the PREDIMED (PREvención con DIeta MEDiterránea)-Plus clinical trial, are: (i) Explore the association between fecal microbiota, body mass index and changes in total body weight after 12-month lifestyle intervention in elderly subjects (aged 55–75 years) with overweight/obesity and metabolic syndrome; (ii) explore the association between fecal microbiota and insulin resistance, estimated by HOMA-IR index, in non-diabetic subjects from the same cohort. Results shown specific fecal microbiota genera associated with lower body mass index and higher weight loss at 12-month follow-up. Specific genera and related metabolic pathways were negatively associated with higher HOMA-IR index and linked with improved glucose homeostasis via increased amino acid breakdown and sulfate reduction. Besides, specific genera and related metabolic pathways were positively associated with HOMA-IR index and linked to increased saccharide degradation inducing abnormal butyrate production. Our results support the identification of specific gut microbiota taxa to predict obesity treatments’ success, but also to target potential bacterial candidates for the development of therapies for insulin resistance. These findings encourage further investigation especially in terms of deepen taxonomic exploration and metabolomics profiling.
Alterations in gut microbial composition and functionality may contribute to the development of obesity and insulin resistance. The identification of specific gut bacteria and metabolic pathways associated with obesity and related metabolic disorders represents a promising novel perspective to tailor personalized interventions. The main objectives of this doctoral thesis, designed within the frame of the PREDIMED (PREvención con DIeta MEDiterránea)-Plus clinical trial, are: (i) Explore the association between fecal microbiota, body mass index and changes in total body weight after 12-month lifestyle intervention in elderly subjects (aged 55–75 years) with overweight/obesity and metabolic syndrome; (ii) explore the association between fecal microbiota and insulin resistance, estimated by HOMA-IR index, in non-diabetic subjects from the same cohort. Results shown specific fecal microbiota genera associated with lower body mass index and higher weight loss at 12-month follow-up. Specific genera and related metabolic pathways were negatively associated with higher HOMA-IR index and linked with improved glucose homeostasis via increased amino acid breakdown and sulfate reduction. Besides, specific genera and related metabolic pathways were positively associated with HOMA-IR index and linked to increased saccharide degradation inducing abnormal butyrate production. Our results support the identification of specific gut microbiota taxa to predict obesity treatments’ success, but also to target potential bacterial candidates for the development of therapies for insulin resistance. These findings encourage further investigation especially in terms of deepen taxonomic exploration and metabolomics profiling.