Abstract
The human gastrointestinal tract (GIT) is inhabited by a vast amount of
microorganisms from different domains of life collectively denominated the gut
microbiome (GM). Among its numerous functions, GM plays a crucial role in
developing the immune system in early-life and contributes to maintain a balanced
metabolism later in life. During the last decade, studies have revealed that imbalances
in GM composition, typically known as dysbiosis, are able to trigger metabolic (and
immunological) abnormalities in the host. This has been demonstrated to have
implications on the development of metabolic disorders, such as obesity, elevated
blood pressure, high serum triglycerides, low high-density lipoprotein (HDL) levels
and insulin resistance, which constitute a cluster of risk factors for development of the
so-called metabolic syndrome (MetS). In turn, these disorders may also influence
muscle composition, physiological decline and frailty in older individuals (e.g. +65
years). Identifying lifestyle factors and their interactions with GM and host would be
of great societal value in relation to preventing frailty and improving the life quality of
the individuals, as well as for economical reasons. Our work gathers an overview on
current methodologies for GM screening, with particular emphasis on viral
communities, it presents an integrative approach to elucidate the interplay of dietary
aspects and GM composition in relation to physiological decline, and finally, it
provides insights of the putative role of viral communities in modulating GM and
metabolic biomarkers in older subjects.
In the first manuscript, we assessed and optimized two methods for phageextraction
based on tangential-flow filtration (TFF) and polyethylene glycol
precipitation (PEG). Through our improved procedures, we reported significantly
higher yields of extracellular viral-like particles (eVLPs) and their DNA, which
allowed proper assessment of their morphological profiles and a higher yield of phageaffiliated
sequences in the metagenome dataset.
In the second manuscript, we aimed at characterizing factors and possible
mechanisms involved in the physiological decline in older subjects by investigating
questionnaires on food-choices, dietary records, GM, metabolome and
anthropometric/body-composition measurements (ABCm). Here, we demonstrated that
the 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 gut
of older adults, we performed a co-abundance analysis of metagenome sequencing of
eVLPs and bacterial members as determined by high-throughput 16S rRNA gene
amplicon sequencing. We demonstrated that phage-bacteria interactions correspond
with variations in the metabolic potential of the GM, as well as levels of HDL and
estimated Glomerular filtration rate (eGFR). Two biomarkers often used to predict the
risk of developing metabolic syndrome.
In this thesis, we present a comprehensive overview of factors (and insights of
putative mechanisms) influencing GM composition amid older individuals, its
connotations on host metabolic and physiological conditions, methodologies, as well as
future prospect of our findings. The current work constitutes one step forward in the
race of understanding the trajectory and interactions of the GM in older subjects and
their implications on well-being.
microorganisms from different domains of life collectively denominated the gut
microbiome (GM). Among its numerous functions, GM plays a crucial role in
developing the immune system in early-life and contributes to maintain a balanced
metabolism later in life. During the last decade, studies have revealed that imbalances
in GM composition, typically known as dysbiosis, are able to trigger metabolic (and
immunological) abnormalities in the host. This has been demonstrated to have
implications on the development of metabolic disorders, such as obesity, elevated
blood pressure, high serum triglycerides, low high-density lipoprotein (HDL) levels
and insulin resistance, which constitute a cluster of risk factors for development of the
so-called metabolic syndrome (MetS). In turn, these disorders may also influence
muscle composition, physiological decline and frailty in older individuals (e.g. +65
years). Identifying lifestyle factors and their interactions with GM and host would be
of great societal value in relation to preventing frailty and improving the life quality of
the individuals, as well as for economical reasons. Our work gathers an overview on
current methodologies for GM screening, with particular emphasis on viral
communities, it presents an integrative approach to elucidate the interplay of dietary
aspects and GM composition in relation to physiological decline, and finally, it
provides insights of the putative role of viral communities in modulating GM and
metabolic biomarkers in older subjects.
In the first manuscript, we assessed and optimized two methods for phageextraction
based on tangential-flow filtration (TFF) and polyethylene glycol
precipitation (PEG). Through our improved procedures, we reported significantly
higher yields of extracellular viral-like particles (eVLPs) and their DNA, which
allowed proper assessment of their morphological profiles and a higher yield of phageaffiliated
sequences in the metagenome dataset.
In the second manuscript, we aimed at characterizing factors and possible
mechanisms involved in the physiological decline in older subjects by investigating
questionnaires on food-choices, dietary records, GM, metabolome and
anthropometric/body-composition measurements (ABCm). Here, we demonstrated that
the 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 gut
of older adults, we performed a co-abundance analysis of metagenome sequencing of
eVLPs and bacterial members as determined by high-throughput 16S rRNA gene
amplicon sequencing. We demonstrated that phage-bacteria interactions correspond
with variations in the metabolic potential of the GM, as well as levels of HDL and
estimated Glomerular filtration rate (eGFR). Two biomarkers often used to predict the
risk of developing metabolic syndrome.
In this thesis, we present a comprehensive overview of factors (and insights of
putative mechanisms) influencing GM composition amid older individuals, its
connotations on host metabolic and physiological conditions, methodologies, as well as
future prospect of our findings. The current work constitutes one step forward in the
race of understanding the trajectory and interactions of the GM in older subjects and
their implications on well-being.
| Originalsprog | Engelsk |
|---|
| Forlag | Department of Food Science, Faculty of Science, University of Copenhagen |
|---|---|
| Status | Udgivet - 2017 |