TY - BOOK

T1 - Towards understanding the trajectory and interactions of the gut microbiome in healthy older humans

AU - Castro Mejia, Josue Leonardo

PY - 2017

Y1 - 2017

N2 - The human gastrointestinal tract (GIT) is inhabited by a vast amount ofmicroorganisms from different domains of life collectively denominated the gutmicrobiome (GM). Among its numerous functions, GM plays a crucial role indeveloping the immune system in early-life and contributes to maintain a balancedmetabolism later in life. During the last decade, studies have revealed that imbalancesin GM composition, typically known as dysbiosis, are able to trigger metabolic (andimmunological) abnormalities in the host. This has been demonstrated to haveimplications on the development of metabolic disorders, such as obesity, elevatedblood pressure, high serum triglycerides, low high-density lipoprotein (HDL) levelsand insulin resistance, which constitute a cluster of risk factors for development of theso-called metabolic syndrome (MetS). In turn, these disorders may also influencemuscle composition, physiological decline and frailty in older individuals (e.g. +65years). Identifying lifestyle factors and their interactions with GM and host would beof great societal value in relation to preventing frailty and improving the life quality ofthe individuals, as well as for economical reasons. Our work gathers an overview oncurrent methodologies for GM screening, with particular emphasis on viralcommunities, it presents an integrative approach to elucidate the interplay of dietaryaspects and GM composition in relation to physiological decline, and finally, itprovides insights of the putative role of viral communities in modulating GM andmetabolic biomarkers in older subjects.In the first manuscript, we assessed and optimized two methods for phageextractionbased on tangential-flow filtration (TFF) and polyethylene glycolprecipitation (PEG). Through our improved procedures, we reported significantlyhigher yields of extracellular viral-like particles (eVLPs) and their DNA, whichallowed proper assessment of their morphological profiles and a higher yield of phageaffiliatedsequences in the metagenome dataset.In the second manuscript, we aimed at characterizing factors and possiblemechanisms involved in the physiological decline in older subjects by investigatingquestionnaires on food-choices, dietary records, GM, metabolome andanthropometric/body-composition measurements (ABCm). Here, we demonstrated thatthe early-onset of physiological decline is partly explained by food-selectivity(pickiness) and associated patterns of carbohydrates’ consumption (and total energy),reflecting changes in GM composition that corresponded with signs of glucoseintolerance.Lastly, in order to gain understanding on the role of viral communities in the gutof older adults, we performed a co-abundance analysis of metagenome sequencing ofeVLPs and bacterial members as determined by high-throughput 16S rRNA geneamplicon sequencing. We demonstrated that phage-bacteria interactions correspondwith variations in the metabolic potential of the GM, as well as levels of HDL andestimated Glomerular filtration rate (eGFR). Two biomarkers often used to predict therisk of developing metabolic syndrome.In this thesis, we present a comprehensive overview of factors (and insights ofputative mechanisms) influencing GM composition amid older individuals, itsconnotations on host metabolic and physiological conditions, methodologies, as well asfuture prospect of our findings. The current work constitutes one step forward in therace of understanding the trajectory and interactions of the GM in older subjects andtheir implications on well-being.

AB - The human gastrointestinal tract (GIT) is inhabited by a vast amount ofmicroorganisms from different domains of life collectively denominated the gutmicrobiome (GM). Among its numerous functions, GM plays a crucial role indeveloping the immune system in early-life and contributes to maintain a balancedmetabolism later in life. During the last decade, studies have revealed that imbalancesin GM composition, typically known as dysbiosis, are able to trigger metabolic (andimmunological) abnormalities in the host. This has been demonstrated to haveimplications on the development of metabolic disorders, such as obesity, elevatedblood pressure, high serum triglycerides, low high-density lipoprotein (HDL) levelsand insulin resistance, which constitute a cluster of risk factors for development of theso-called metabolic syndrome (MetS). In turn, these disorders may also influencemuscle composition, physiological decline and frailty in older individuals (e.g. +65years). Identifying lifestyle factors and their interactions with GM and host would beof great societal value in relation to preventing frailty and improving the life quality ofthe individuals, as well as for economical reasons. Our work gathers an overview oncurrent methodologies for GM screening, with particular emphasis on viralcommunities, it presents an integrative approach to elucidate the interplay of dietaryaspects and GM composition in relation to physiological decline, and finally, itprovides insights of the putative role of viral communities in modulating GM andmetabolic biomarkers in older subjects.In the first manuscript, we assessed and optimized two methods for phageextractionbased on tangential-flow filtration (TFF) and polyethylene glycolprecipitation (PEG). Through our improved procedures, we reported significantlyhigher yields of extracellular viral-like particles (eVLPs) and their DNA, whichallowed proper assessment of their morphological profiles and a higher yield of phageaffiliatedsequences in the metagenome dataset.In the second manuscript, we aimed at characterizing factors and possiblemechanisms involved in the physiological decline in older subjects by investigatingquestionnaires on food-choices, dietary records, GM, metabolome andanthropometric/body-composition measurements (ABCm). Here, we demonstrated thatthe early-onset of physiological decline is partly explained by food-selectivity(pickiness) and associated patterns of carbohydrates’ consumption (and total energy),reflecting changes in GM composition that corresponded with signs of glucoseintolerance.Lastly, in order to gain understanding on the role of viral communities in the gutof older adults, we performed a co-abundance analysis of metagenome sequencing ofeVLPs and bacterial members as determined by high-throughput 16S rRNA geneamplicon sequencing. We demonstrated that phage-bacteria interactions correspondwith variations in the metabolic potential of the GM, as well as levels of HDL andestimated Glomerular filtration rate (eGFR). Two biomarkers often used to predict therisk of developing metabolic syndrome.In this thesis, we present a comprehensive overview of factors (and insights ofputative mechanisms) influencing GM composition amid older individuals, itsconnotations on host metabolic and physiological conditions, methodologies, as well asfuture prospect of our findings. The current work constitutes one step forward in therace of understanding the trajectory and interactions of the GM in older subjects andtheir implications on well-being.

UR - https://soeg.kb.dk/permalink/45KBDK_KGL/fbp0ps/alma99121927847605763

M3 - Ph.D. thesis

BT - Towards understanding the trajectory and interactions of the gut microbiome in healthy older humans

PB - Department of Food Science, Faculty of Science, University of Copenhagen

ER -