Perfluoroalkyl substances are increased in patients with late-onset ulcerative colitis and induce intestinal barrier defects ex vivo in murine intestinal tissue.

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.

Differences in Gut Microbiome Composition between Senior Orienteering Athletes and Community-Dwelling Older Adults.

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: The physically active senior orienteers had a more homogeneous microbiota within the group and a higher abundance of Faecalibacterium prausnitzii compared to the community-dwelling older adults. Faecalibacterium prausnitzii has previously shown to have beneficial properties. Senior orienteers also had a lower abundance of Parasutterella excrementihominis and Bilophila 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.

Effects of Dietary Fibres on Acute Indomethacin-Induced Intestinal Hyperpermeability in the Elderly: A Randomised Placebo Controlled Parallel Clinical Trial.

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 ß-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 ß-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.

Simultaneous determination of perfluoroalkyl substances and bile acids in human serum using ultra-high-performance liquid chromatography-tandem mass spectrometry.

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. Graphical Abstract.