The Gut Microbiome of Older Danish Adults – with Particular Focus on the Gut Mycobiome

Hajar Fauzan Bin Ahmad

Research output: Book/ReportPh.D. thesisResearch

Abstract

The human gut is home for plethora of microbes including prokaryotic and eukaryotic organisms across all domains of the tree of life. This complex community is known as the gut microbiome (GM). Nowadays, the advances in high-throughput sequencing technology allow for studies not limited to bacteria, but also fungi, archaea, viruses and parasites in various settings across age groups, life-styles, diets, and geographical regions have been studied. Gut microbial dysbiosis have been linked to frailty in elderly, but their possible association with host health is little understood. During the course of life, imbalances in the GM is associated with significant phenotypic effects for the host such as development of metabolic disorders like obesity, elevated blood pressure, changes in serum lipids and sugar metabolism, infections, overall losses of muscle mass and functional and general physiological decline. Understanding how these disorders have been orchestrated by the interplay between prokaryotic and eukaryotic communities is of great interest with the aim of elucidating mechanistic approaches to prevent frailty and improve quality of life through healthy ageing. Generally, our work involves high throughput sequencing and conventional microbiology-based approaches for GM characterization, with special focus on prokaryote andeukaryote communities in association with dietary, metabolome, life-styles and clinical characteristics at baseline and during a 1-year intervention study investigating the effect of whey supplementation and physical training activity. The backbone of this thesis formed based on designated theoretical and experimental aspects related to GM studies among the older Danish adults – in which the story was elaborated in six manuscripts as follow; The Manuscript 1 mainly covers an interdisciplinary research effort on Counteracting Agerelated Loss of Skeletal Muscle Mass (CALM) to investigate the impact of lifestyle changes on physical and functional outcomes as well as everyday practices and habits in a qualitative context. For this thesis, we discuss a proposed approach for characterization of the GM by employing tagencoded 16S ribosomal RNA gene (prokaryotes) and internal transcribed spacer region (eukaryotes) high-throughput sequencing using the MiSeq and NextSeq platform, and plasma and faecal metabolite analysis by performing gas chromatography with time-of-flight mass spectrometry andnuclear magnetic resonance spectroscopy. Hence, this manuscript formed relevant methodologies for elucidating how GM and metabolomes as integral components for this thesis. In addition, we applied conventional culturing method on selected samples from the CALM cohort, coupling with nextgeneration sequencing (NGS) by performing whole genome sequencing on an isolated bacteria species namely Streptococcus anginosus. The draft genome of this bacteria is reported in the Manuscript 2.Next, the Manuscript 3 is a meta-analysis study intended to uncover the multidisciplina ry biography of whey protein – reflecting the sensory qualities and challenges, overview into its cultural history, its nutritional value and effects on the human body and the perception by people who consume based in the field of food studies. Here, we reviewed the effect of different combinations of whey protein supplements and exercise on the muscle mass, GM and metabolome of the elderly Danes during the intervention part of CALM. In the Manuscript 4, we demonstrated studies related to bacteria as biggest component of GM community structure. Specifically, we aimed at characterizing the prokaryote communities based on physical fitness groups in older adults of Danes by investigating questionnaires on food-choices, dietary records, prokaryotes compositions, metabolome and anthropometric/body-compositionmeasurements. Hence, the study elucidated an early trajectory of physiological decline as explained by dietary habits, mirroring changes in GM composition, metabolome and blood-clinical parameters. Later on, Manuscript 5 attempts to identify gut microbial fungal associations with the progression of atherogenic dyslipidemia in a population of older adults by investigating the interplay between dietary intake, gut mycobiome composition, plasma and faecal metabolome and anthropometric/body-composition measurements of 100 older adult of Danes. We demonstrated that gut mycobiome dysbiosis on older adults is associated with hypertriglyceridemia - a known risk factor for development of cardiovascular disease. These likely explained by a higher dietary fat intake that corresponded with elevated levels of lipids such as triglycerides and very low-density lipoproteinamong hypertriglyceridemia older individuals. Lastly, in order to gain understanding on the stability of mycobiome among the older adults, we explored the effect of whey-diet and exercise in for 1 year intervention (at Baseline, 6-months and 12-months points of time). We observed that the gut mycobiome of elderly Danesis rather stable over the 12 months intervention period (Manuscript 6). With these research efforts I hope to prime the microbiome field for future healthy ageing initiatives.
Original languageEnglish
PublisherDepartment of Food Science, Faculty of Science, University of Copenhagen
Number of pages199
Publication statusPublished - 2019

Cite this