To Örebro University

Many of the increasing number of community-dwelling older adults will need increased healthcare in the future. By characterising gut health and its association with wellbeing and nutrient intake in this population, we aim to recognise areas along the gut-brain axis through which the health of community-dwelling older adults might be promoted. In this cross-sectional observational study, validated questionnaires were used to assess gut health, nutrient intake, and wellbeing in 241 community-dwelling older adults (>= 65 years old). In total, 65% of the participants experienced at least one gastrointestinal symptom, of which females had more abdominal pain and constipation, while the oldest old (i.e., >= 80 years old) had more diarrhoea. Increased gastrointestinal symptoms correlated with more stress, anxiety, depression, and a decreased quality of life, in addition to dyspepsia which correlated with a lower E% of protein. Most of the participants did not reach the recommended intake for protein, fibre and polyunsaturated fats. Males had a lower intake of protein (E%) and fibre (g/MJ) than females, and the oldest old had a lower E% of protein than younger older adults. In conclusion, our results demonstrate that gastrointestinal symptoms are common, and most of the study participants had an imbalanced macronutrient intake, which could be a target for future possible dietary interventions to improve overall health.

There is a global ageing phenomenon, which stress the importance for an improved health for the increased population of older adults. One important factor for a good health is a well-functioning gut. Hence, this thesisinvestigates several aspects of gut health for older adults, spanning from overall gut health in community-dwelling older adults, to investigating a gut disease model: inflammatory bowel disease, which includes Crohn’s disease and ulcerative colitis. 

When investigating community-dwelling older adults, gastrointestinal symptoms were found to be common and correlated to a lower experience of well-being. In addition, more than half of the population did not reach the recommended intake of several macronutrients, including protein and fibre. Compared to a group of active older adults, still practising orienteering, i.e., senior orienteers, community-dwelling older adult’s further showed signs of a less healthier gut microbiota, including lower levels of Faecalibacterium prausnitzii.

By investigating the disease model of inflammatory bowel disease, later onset of Crohn’s disease seemed to have less hyperresponsive adaptive immune response toward the own gut microbiota, which seems to be due to a less genetic predisposition among later onset individuals. Interestingly, an environmental pollutant, per- and polyfluoroalkyl substances (PFAS), was increased in the serum of late-onset ulcerative colitis patients compared to healthy controls. A higher level of PFAS further correlated to a disturbed bile acid pool. In addition, PFAS induced an increased intestinal permeability across ileal and colonic murine tissue. 

In conclusion, the work included in this thesis further emphasises the importance of a maintained gut health. In addition, the work highlights diet, an active life-style, gut microbiota and environmental factors, for example PFAS, as targets of future interventions studies with the aim to improve gut health and overall health among older adults. 

BACKGROUND: Environmental factors are strongly implicated in late-onset of inflammatory bowel disease. Here, we investigate whether high levels of perfluoroalkyl substances are associated with (1) late-onset inflammatory bowel disease, and (2) disturbances of the bile acid pool. We further explore the effect of the specific perfluoroalkyl substance perfluorooctanoic acid on intestinal barrier function in murine tissue.

METHODS: Serum levels of perfluoroalkyl substances and bile acids were assessed by ultra-performance liquid chromatography coupled to a triple-quadrupole mass spectrometer in matched samples from patients with ulcerative colitis (n = 20) and Crohn's disease (n = 20) diagnosed at the age of ≥55 years. Age and sex-matched blood donors (n = 20), were used as healthy controls. Ex vivo Ussing chamber experiments were performed to assess the effect of perfluorooctanoic acid on ileal and colonic murine tissue (n = 9).

RESULTS: The total amount of perfluoroalkyl substances was significantly increased in patients with ulcerative colitis compared to healthy controls and patients with Crohn's disease (p < .05). Ex vivo exposure to perfluorooctanoic acid induced a significantly altered ileal and colonic barrier function. The distribution of bile acids, as well as the correlation pattern between (1) perfluoroalkyl substances and (2) bile acids, differed between patient and control groups.

DISCUSSION: Our results demonstrate that perfluoroalkyl substances levels are increased in patients with late-onset ulcerative colitis and may contribute to the disease by inducing a dysfunctional intestinal barrier.

BACKGROUND: Gastrointestinal (GI) health is an important aspect of general health. Gastrointestinal symptoms are of specific importance for the elderly, an increasing group globally. Hence, promoting the elderly's health and especially gastrointestinal health is important. Gut microbiota can influence gastrointestinal health by modulation of the immune system and the gut-brain axis. Diverse gut microbiota have been shown to be beneficial; however, for the elderly, the gut microbiota is often less diverse. Nutrition and physical activity, in particular, are two components that have been suggested to influence composition or diversity.

MATERIALS AND METHODS: In this study, we compared gut microbiota between two groups of elderly individuals: community-dwelling older adults and physically active senior orienteering athletes, where the latter group has less gastrointestinal symptoms and a reported better well-being. With this approach, we explored if certain gut microbiota were related to healthy ageing. The participant data and faecal samples were collected from these two groups and the microbiota was whole-genome sequenced and taxonomically classified with MetaPhlAn.

RESULTS: unclassified, which have been associated with impaired GI health. We could not observe any difference between the groups in terms of Shannon diversity index. Interestingly, a subgroup of community-dwelling older adults showed an atypical microbiota profile as well as the parameters for gastrointestinal symptoms and well-being closer to senior orienteers.

CONCLUSIONS: Our results suggest specific composition characteristics of healthy microbiota in the elderly, and show that certain components of nutrition as well as psychological distress are not as tightly connected with composition or diversity variation in faecal microbiota samples.

The effect of dietary fibres on intestinal barrier function has not been well studied, especially in the elderly. We aimed to investigate the potential of the dietary fibres oat beta-glucan and wheat arabinoxylan to strengthen the intestinal barrier function and counteract acute non-steroid anti-inflammatory drug (indomethacin)-induced hyperpermeability in the elderly. A general population of elderly subjects (>= 65 years,n= 49) was randomised to a daily supplementation (12g/day) of oat beta-glucan, arabinoxylan or placebo (maltodextrin) for six weeks. The primary outcome was change in acute indomethacin-induced intestinal permeability from baseline, assessed by an in vivo multi-sugar permeability test. Secondary outcomes were changes from baseline in: gut microbiota composition, systemic inflammatory status and self-reported health. Despite a majority of the study population (85%) showing a habitual fibre intake below the recommendation, no significant effects on acute indomethacin-induced intestinal hyperpermeability in vivo or gut microbiota composition were observed after six weeks intervention with either dietary fibre, compared to placebo.

There is evidence of a positive association between per- and polyfluoroalkyl substances (PFASs) and cholesterol levels in human plasma, which may be due to common reabsorption of PFASs and bile acids (BAs) in the gut. Here we report development and validation of a method that allows simultaneous, quantitative determination of PFASs and BAs in plasma, using 150 μL or 20 μL of sample. The method involves protein precipitation using 96-well plates. The instrumental analysis was performed with ultra-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS), using reverse-phase chromatography, with the ion source operated in negative electrospray mode. The mass spectrometry analysis was carried out using multiple reaction monitoring mode. The method proved to be sensitive, robust, and with sufficient linear range to allow reliable determination of both PFASs and BAs. The method detection limits were between 0.01 and 0.06 ng mL^-1 for PFASs and between 0.002 and 0.152 ng mL^-1 for BAs, with the exception of glycochenodeoxycholic acid (0.56 ng mL^-1). The PFAS measured showed excellent agreement with certified plasma PFAS concentrations in NIST SRM 1957 reference serum. The method was tested on serum samples from 20 healthy individuals. In this proof-of-concept study, we identified significant associations between plasma PFAS and BA levels, which suggests that PFAS may alter the synthesis and/or uptake of BAs.