Contribución funcional y metabólica de la microbiota intestinal a la ingesta energética en el desarrollo de la obesidad

  1. Acuña Morales, Inmaculada
Supervised by:
  1. Antonio Suárez García Co-director
  2. Margarita Aguilera Gómez Co-director
  3. Cristina Campoy Folgoso Co-director

Defence university: Universidad de Granada

Fecha de defensa: 09 May 2022

Committee:
  1. A. Muñoz Hoyos Chair
  2. María del Carmen Ramírez Tortosa Secretary
  3. Daniel Aguirre de Cárcer García Committee member
  4. Elena Gonzalez-Rey Committee member
  5. Simone Rampelli Committee member
Department:
  1. BIOQUÍMICA Y BIOLOGÍA MOLECULAR II

Type: Thesis

Abstract

Human gut microbiota is a dense and diverse microbial community that contributes greatly to the health and disease balance. Gut microbial communities have co-evolved with the host to develop a mutualistic relationship, influencing metabolic homeostasis, the endocrine system, brain function, and macronutrient availability. Early life stages are of exceptional interest, because the establishment and influence of the gut taxa microbiota can trigger long-term health consequences. The increased knowledge about the intestinal microbiota is producing a change of paradigm and focus of the studies, which were previously used to answer the question of what intestinal microbiota is producing?, towards the question what function do these microbes have? To try to answer these questions, a metabolic and enzymatic study has been carried out to better describe the effects of the intestinal microbiota on the host health/disease equilibrium, specifically in obesity and cognitive alterations; and to design a rational strategy to classify, identify and test microbiota consortia in gnotobiotic murine models. Specially, the study has focused on glycosidase enzymatic activity, its impact on carbohydrate metabolism, in relation to obesity. Likewise, the relationship of the microbiota with childhood neurodevelopment through histidine metabolism has been studied. That has been facilitated throught the development of a specific, rapid, precise and simultaneous method to measure histidine and its bioactive metabolites using UHPLC-MS/ MS. The overall results show that the obesity phenotype is transmitted from mother-child-mouse through the effective transfer of the microbiota. In addition, specific microbial metabolism is associated with the neurodevelopmental profile of children, and the association was maintained in microbiota recipient mice, showing significant differences in the histidine metabolism. Therefore, contribution and more scientific evidence for knowing the communication pathways between the microbiota and the host is the way to better understand their influence on metabolic and neurological disorders and ultimately on health in order to find new therapeutic and diagnostic approaches.