| 1. |
- Fart, Frida, 1992-, et al.
(författare)
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Differences in Gut Microbiome Composition between Senior Orienteering Athletes and Community-Dwelling Older Adults
- 2020
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Ingår i: Nutrients. - : MDPI. - 2072-6643. ; 12:9
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Fart, Frida, 1992-, et al.
(författare)
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Gut Health and Its Association with Wellbeing and Nutrient Intake in Community-Dwelling Older Adults
- 2022
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Ingår i: Gastroenterology Insights. - : MDPI. - 2036-7414 .- 2036-7422. ; 13:4, s. 349-364
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 3. |
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| 4. |
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| 5. |
- Ganda Mall, John-Peter, 1988-, et al.
(författare)
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Are self-reported gastrointestinal symptoms among older adults associated with increased intestinal permeability and psychological distress?
- 2018
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Ingår i: BMC Geriatrics. - : BioMed Central. - 1471-2318. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Despite the substantial number of older adults suffering from gastrointestinal (GI) symptoms little is known regarding the character of these complaints and whether they are associated with an altered intestinal barrier function and psychological distress. Our aim was to explore the relationship between self-reported gut health, intestinal permeability and psychological distress among older adults.METHODS: Three study populations were included: 1) older adults with GI symptoms (n = 24), 2) a group of older adults representing the general elderly population in Sweden (n = 22) and 3) senior orienteering athletes as a potential model of healthy ageing (n = 27). Questionnaire data on gut-health, psychological distress and level of physical activity were collected. Intestinal permeability was measured by quantifying zonulin in plasma. The level of systemic and local inflammation was monitored by measuring C-reactive protein (CRP), hydrogen peroxide in plasma and calprotectin in stool samples. The relationship between biomarkers and questionnaire data in the different study populations was illustrated using a Principal Component Analysis (PCA).RESULTS: Older adults with GI symptoms displayed significantly higher levels of both zonulin and psychological distress than both general older adults and senior orienteering athletes. The PCA analysis revealed a separation between senior orienteering athletes and older adults with GI symptoms and showed an association between GI symptoms, psychological distress and zonulin.CONCLUSIONS: Older adults with GI symptoms express increased plasma levels of zonulin, which might reflect an augmented intestinal permeability. In addition, this group suffer from higher psychological distress compared to general older adults and senior orienteering athletes. This relationship was further confirmed by a PCA plot, which illustrated an association between GI symptoms, psychological distress and intestinal permeability.
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| 6. |
- Ganda Mall, John Peter, 1988-, et al.
(författare)
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Differential effects of dietary fibres on colonic barrier function in elderly individuals with gastrointestinal symptoms
- 2018
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Gastrointestinal problems are common in elderly and often associated with psychological distress and increased levels of corticotrophin-releasing hormone, a hormone known to cause mast cell (MC) degranulation and perturbed intestinal barrier function. We investigated if dietary fibres (non-digestible polysaccharides [NPS]) could attenuate MC-induced colonic hyperpermeability in elderly with gastrointestinal (GI) symptoms. Colonic biopsies from elderly with diarrhoea and/or constipation (n = 18) and healthy controls (n = 19) were mounted in Ussing chambers and pre-stimulated with a yeast-derived beta (β)-glucan (0.5 mg/ml) or wheat-derived arabinoxylan (0.1 mg/ml) before the addition of the MC-degranulator Compound (C) 48/80 (10 ng/ml). Permeability markers were compared pre and post exposure to C48/80 in both groups and revealed higher baseline permeability in elderly with GI symptoms. β-glucan significantly attenuated C48/80-induced hyperpermeability in elderly with GI symptoms but not in healthy controls. Arabinoxylan reduced MC-induced paracellular and transcellular hyperpermeability across the colonic mucosa of healthy controls, but did only attenuate transcellular permeability in elderly with GI symptoms. Our novel findings indicate that NPS affect the intestinal barrier differently depending on the presence of GI symptoms and could be important in the treatment of moderate constipation and/or diarrhoea in elderly.
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| 7. |
- Ganda Mall, John Peter, 1988-, et al.
(författare)
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Effects of Dietary Fibres on Acute Indomethacin-Induced Intestinal Hyperpermeability in the Elderly : A Randomised Placebo Controlled Parallel Clinical Trial
- 2020
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Ingår i: Nutrients. - : MDPI. - 2072-6643. ; 12:7
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 8. |
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| 9. |
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| 10. |
- Keita, Åsa, et al.
(författare)
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Gut barrier dysfunction : a primary defect in twins with Crohn's disease predominantly caused by genetic predisposition
- 2018
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Ingår i: Journal of Crohn's & Colitis. - : Elsevier. - 1873-9946 .- 1876-4479. ; 12:10, s. 1200-1209
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: The aetiology of Crohn's disease is poorly understood. By investigating twin pairs discordant for Crohn's disease we aimed to assess if the dysregulated barrier represents a cause or a consequence of inflammation and to evaluate the impact of genetic predisposition on barrier function.Methods: Ileal biopsies from 15 twin pairs discordant for Crohn's disease (monozygotic n=9, dizygotic n=6) and 10 external controls were mounted in Ussing chambers to assess paracellular permeability to51Chromium (Cr)-EDTA and trancellular passage to non-pathogenic E. coli K-12. Experiments were performed with and without provocation with acetylsalicylic acid. Immunofluorescence and ELISA were used to quantify the expression level of tight junction proteins.Results: Healthy co-twins and affected twins displayed increased 51Cr-EDTA permeability at 120 min both with Acetylsalicylic acid (p<0.001) and without (p<0.001) when compared to controls. A significant increase in 51Cr-EDTA flux was seen already at 20 minutes in healthy monozygotic co-twins compared to controls (p≤0.05) when stratified by zygosity, but not in healthy dizygotic co-twins. No difference in E. coli passage was observed between groups. Immunofluorescence of the tight junction proteins claudin-5 and tricellulin showed lower levels in healthy co-twins (p<0.05) and affected twins (p<0.05) compared to external controls, while ELISA only showed lower tricellulin in Crohn's disease twins (p<0.05).Conclusion: Our results suggest that barrier dysfunction is a primary defect in Crohn's disease, since changes were predominantly seen in healthy monozygotic co-twins. Passage of E. coli seems to be a consequence of inflammation rather than representing a primary defect.
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| 11. |
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| 12. |
- Rajan, Sukithar K., 1978-, et al.
(författare)
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Phylogenetic microbiota profiling in fecal samples depends on combination of sequencing depth and choice of NGS analysis method
- 2019
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Ingår i: PLOS ONE. - : PLOS. - 1932-6203. ; 14:9
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Tidskriftsartikel (refereegranskat)abstract
- The human gut microbiota is well established as an important factor in health and disease. Fecal sample microbiota are often analyzed as a proxy for gut microbiota, and characterized with respect to their composition profiles. Modern approaches employ whole genome shotgun next-generation sequencing as the basis for these analyses. Sequencing depth as well as choice of next-generation sequencing data analysis method constitute two main interacting methodological factors for such an approach. In this study, we used 200 million sequence read pairs from one fecal sample for comparing different taxonomy classification methods, using default and custom-made reference databases, at different sequencing depths. A mock community data set with known composition was used for validating the classification methods. Results suggest that sequencing beyond 60 million read pairs does not seem to improve classification. The phylogeny prediction pattern, when using the default databases and the consensus database, appeared to be similar for all three methods. Moreover, these methods predicted rather different species. We conclude that the choice of sequencing depth and classification method has important implications for taxonomy composition prediction. A multi-method-consensus approach for robust gut microbiota NGS analysis is recommended.
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| 13. |
- Östlund-Lagerström, Lina, 1984-, et al.
(författare)
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Senior orienteering athletes as a model of healthy aging : a mixed-method approach
- 2015
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Ingår i: BMC Geriatrics. - : Springer Science and Business Media LLC. - 1471-2318. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: The proportion of individuals reaching an old age is increasing and will, in the near future consume a majority of health care resources. It is therefore essential to facilitate the maintenance of optimal functionality among older adults. By characterizing older individuals experiencing wellbeing, factors important to promote and maintain health through life can be identified. Orienteering is an endurance-running sport involving cross-country navigation, demanding both cognitive and physical skills of its practitioners. In this study we aim to explore a Swedish population of senior orienteering athletes as a potential model of healthy aging.Methods: We undertook a mixed-method approach using quantitative (i.e. questionnaires) and qualitative (i.e. focus group discussions) methodologies to explore a population of senior orienteering athletes (n = 136, median age = 69 (67-71) years). Quantitative data was collected to evaluate health status, assessing physical activity (Frandin-Grimby activity scale (FGAS)), functional wellbeing (EQ-5D-5 L), gut health (Gastrointestinal symptoms rating scale (GSRS)), anxiety and depression (Hospital Anxiety and Depression scale (HADS)) and overall health (Health index (HI)). The data was further compared to reference values obtained from a free-living Swedish population of older adults. Focus group discussions (FGD) were performed as a complement to the quantitative data to facilitate the individuals' own views on health and physical activity.Results: The orienteering athletes enrolled in the study reported a significantly better health compared to the free-living older adults (p < 0.0015) on all questionnaires except HADS. The high health status displayed in this population was further confirmed by the FGD findings, in which all participants declared their engagement in orienteering as a prerequisite for health.Conclusions: In conclusion our results show that senior orienteering may represent an ideal model in studies of healthy aging. Furthermore, our results show that even though the senior orienteering athletes are well aware of the long-term benefits of physical activity and have practiced the sport from a young age, they particularly point out that their engagement in orienteering is driven by short-term values such as enjoyment and passion. This may be important to consider when introducing public health interventions among the general older population.
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| 14. |
- Algilani, Samal, 1981-, et al.
(författare)
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Exploring the concept of optimal functionality in old age
- 2014
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Ingår i: Journal of Multidisciplinary Healthcare. - : Dove Medical Press. - 1178-2390. ; 7, s. 69-79
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: Aging is characterized by loss of function and represents a perspective that puts the focus on the negative aspects of aging. Thus, it is fundamental to shift the focus from loss of function to maintaining good health and personal satisfaction through life; in other words, to promote optimal functionality at a level appropriate for older adults. However, it is not yet known what constitutes optimal functionality from the older adult's own perspective.OBJECTIVE: To explore the concept of optimal functionality in old age from the older adult's perspective (ie, people over 65 years of age) in industrialized Western countries.METHODS: We undertook a scoping review and searched two electronic databases (PubMed and the Cumulative Index to Nursing and Allied Health Literature [CINAHL]) from January 2002 to July 2013 for scientific studies, using the key search term personal satisfaction. In total, 25 scientific studies were analyzed.RESULTS: Only six of the included articles applied a qualitative methodology. By analyzing the results of these articles, three major themes were identified as cornerstones in the concept of optimal functionality at old age: 1) self-related factors (eg, mental well-being); 2) body-related factors (eg, physical well-being); and 3) external factors equal to demographic and environmental factors.CONCLUSION: There is a lack of qualitative studies in the current literature, and hence of what constitutes optimal functionality from the older adult's perspective. The results outlined in this review identify three cornerstones (self-related factors, body-related factors, and external factors) of what constitutes optimal functionality at old age. However, it is vital that these findings are taken further and are evaluated through qualitative studies to reflect older adults' opinions.
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| 15. |
- Algilani, Samal, 1981-, et al.
(författare)
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Increasing the qualitative understanding of optimal functionality in older adults : a focus group based study
- 2016
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Ingår i: BMC Geriatrics. - London, United Kingdom : BioMed Central. - 1471-2318. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Decreased independence and loss of functional ability are issues regarded as inevitably connected to old age. This ageism may have negative influences on older adults' beliefs about aging, making it difficult for them to focus on their current ability to maintain a good health. It is therefore important to change focus towards promoting Optimal Functionality (OF). OF is a concept putting the older adult's perspective on health and function in focus, however, the concept is still under development. Hence, the aim was to extend the concept of optimal functionality in various groups of older adults.Methods: A qualitative study was conducted based on focus group discussions (FGD). In total 6 FGDs were performed, including 37 older adults from three different groups: group 1) senior athletes, group 2) free living older adults, group 3) older adults living in senior living homes. All data was transcribed verbatim and analyzed following the process of deductive content analysis.Results: The principal outcome of the analysis was "to function as optimally as you possibly can", which was perceived as the core of the concept. Further, the concept of OF was described as multifactorial and several new factors could be added to the original model of OF. Additionally the findings of the study support that all three cornerstones comprising OF have to occur simultaneously in order for the older adult to function as optimal as possible.Conclusions: OF is a multifaceted and subjective concept, which should be individually defined by the older adult. This study further makes evident that older adults as a group are heterogeneous in terms of their preferences and views on health and should thus be approached as such in the health care setting. Therefore it is important to promote an individualized approach as a base when caring for older adults.
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| 16. |
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| 17. |
- Fart, Frida, 1992-, et al.
(författare)
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Perfluoroalkyl substances are increased in patients with late-onset ulcerative colitis and induce intestinal barrier defects ex vivo in murine intestinal tissue
- 2021
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Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 56:11, s. 1286-1295
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 18. |
- Fart, Frida, 1992-
(författare)
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The Ageing Gut, in Health and Disease
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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| 19. |
- Ganda Mall, John-Peter, 1988-, et al.
(författare)
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A β-Glucan-Based Dietary Fiber Reduces Mast Cell-Induced Hyperpermeability in Ileum From Patients With Crohn's Disease and Control Subjects
- 2017
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Ingår i: Inflammatory Bowel Diseases. - : Lippincott-Raven Publishers. - 1078-0998 .- 1536-4844. ; 24:1, s. 166-178
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Tidskriftsartikel (refereegranskat)abstract
- Background: Administration of β-glucan has shown immune-enhancing effects. Our aim was to investigate whether β-glucan could attenuate mast cell (MC)-induced hyperpermeability in follicle-associated epithelium (FAE) and villus epithelium (VE) of patients with Crohn's disease (CD) and in noninflammatory bowel disease (IBD)-controls. Further, we studied mechanisms of β-glucan uptake and effects on MCs in vitro.Methods: Segments of FAE and VE from 8 CD patients and 9 controls were mounted in Ussing chambers. Effects of the MC-degranulator compound 48/80 (C48/80) and yeast-derived β-1,3/1,6 glucan on hyperpermeability were investigated. Translocation of β-glucan and colocalization with immune cells were studied by immunofluorescence. Caco-2-cl1- and FAE-cultures were used to investigate β-glucan-uptake using endocytosis inhibitors and HMC-1.1 to study effects on MCs.Results: β-glucan significantly attenuated MC-induced paracellular hyperpermeability in CD and controls. Transcellular hyperpermeability was only significantly attenuated in VE. Baseline paracellular permeability was higher in FAE than VE in both groups, P<0.05, and exhibited a more pronounced effect by C48/80 and β-glucan P<0.05. No difference was observed between CD and controls. In vitro studies showed increased passage, P<0.05, of β-glucan through FAE-culture compared to Caco-2-cl1. Passage was mildly attenuated by the inhibitor methyl-β-cyclodextrin. HMC-1.1 experiments showed a trend to decreasing MC-degranulation and levels of TNF-α but not IL-6 by β-glucan. Immunofluorescence revealed more β-glucan-uptake and higher percentage of macrophages and dendritic cells close to β-glucan in VE of CD compared to controls.Conclusions: We demonstrated beneficial effects of β-glucan on intestinal barrier function and increased β-glucan-passage through FAE model. Our results provide important and novel knowledge on possible applications of β-glucan in health disorders and diseases characterized by intestinal barrier dysfunction.
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| 20. |
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| 21. |
- Ganda Mall, John-Peter, 1988-
(författare)
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Non-digestible Polysaccharides and Intestinal Barrier Function : specific focus on its efficacy in elderly and patients with Crohn’s disease
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A large number of elderly suffer from gastrointestinal (GI) symptoms such as constipation and diarrhoea. The underlying mechanisms of age-acquired GI symptoms are not well studied but are necessary to clarify in order to recommend the right treatment. Non-digestible polysaccharides (NPS) are dietary fibres that could have beneficial effects on the intestinal immune system and barrier function, although their efficacy needs to be evaluated. Paper I showed that elderly with GI symptoms have significantly higher small intestinal permeability than a general elderly population, along with a stronger association to psychological distress. In Paper II we performed a randomised controlled trial with a general population of elderly that consumed either placebo, the NPS’s arabinoxylan or oat β-glucan for a period of 6 weeks. No protective effects were observed related to indomethacin-induced intestinal hyperpermeability, inflammatory markers, or self-reported health if compared to placebo. Paper III showed that stimulation with a yeast-derived β-glucan significantly attenuated Compound (C) 48/80-induced hyperpermeability in colonic biopsies from elderly with GI symptoms mounted in Ussing chambers, but not in young healthy adults. Arabinoxylan attenuated only C48/80-induced transcellular permeability in elderly but both paracellular and transcellular permeability in young healthy adults. Paper IV showed that the same yeast-derived β-glucan from paper III could cross the epithelium of ileal tissues from patients with Crohn’s disease (CD) and non-CD controls, mounted in Ussing chambers, and attenuate C48/80-induced hyperpermeability. In conclusion, we found that elderly with GI symptoms display a deteriorated barrier function and that administration of selective NPS can have beneficial effect on intestinal permeability in selective populations.
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| 22. |
- Gullberg, Elisabet, et al.
(författare)
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Yersinia pseudotuberculosis induces transcytosis of nanoparticles across human intestinal villus epithelium via invasin-dependent macropinocytosis
- 2008
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Ingår i: Laboratory investigation; a journal of technical methods and pathology. - New York, USA : Elsevier BV. - 1530-0307 .- 0023-6837. ; 88:11, s. 1215-26
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Tidskriftsartikel (refereegranskat)abstract
- Crohn's disease is characterized by a defect in intestinal barrier function, where bacteria are considered the most important inflammation-driving factor. Enteric bacteria, including E. coli and Yersinia spp, affect tight junctions in enterocytes, but little is known about bacterial effects on the transcellular pathway. Our objective was to study the short-term effects of Y. pseudotuberculosis on uptake of nanoparticles across human villus epithelium. Monolayers of human colon epithelium-derived Caco-2 cells and biopsies of normal human ileum were studied after 2 h exposure to Y. pseudotuberculosis expressing (inv+) or lacking (inv-) the bacterial adhesion molecule, invasin. Transepithelial transport of fluorescent nanoparticles (markers of transcytosis) was quantified by flow cytometry, and mechanisms explored by using inhibitors of endocytosis. Epithelial expressions of beta1-integrin and particle uptake pathways were studied by confocal microscopy. The paracellular pathway was assessed by electrical resistance (TER), mannitol flux, and expression of tight junction proteins occludin and caludin-4 by confocal microscopy. Inv+ Y. pseudotuberculosis adhered to the apical surface of epithelial cells and induced transcytosis of exogenous nanoparticles across Caco-2 monolayers (30-fold increase, P<0.01) and ileal mucosa (268+/-47% of control; P<0.01), whereas inv bacteria had no effect on transcytosis. The transcytosis was concentration-, particle size- and temperature-dependent, and possibly mediated via macropinocytosis. Y. pseudotuberculosis also induced apical expression of beta1-integrin on epithelial cells. A slight drop in TER was seen after exposure to inv+ Y. pseudotuberculosis, whereas mannitol flux and tight junction protein expression was unchanged. In summary, Y. pseudotuberculosis induced apical expression of beta1-integrin and stimulated uptake of nanoparticles via invasin-dependent transcytosis in human intestinal epithelium. Our findings suggest that bacterial factors may initiate transcytosis of luminal exogenous particles across human ileal mucosa, thus presenting a novel mechanism of intestinal barrier dysfunction.
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| 23. |
- Halfvarson, Jonas, 1970-, et al.
(författare)
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Genetic and shared environmental risk factors do not lead to eosinophil activation in healthy twins of IBD patients
- 2020
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Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 55:10, s. 1163-1170
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To examine the role of eosinophils in the pre-diagnostic phase of inflammatory bowel disease (IBD), we studied the influence of genetic and shared environmental risk factors in a twin cohort of IBD.Material and methods: We analysed eosinophil derived neurotoxin (EDN) and eosinophil cationic protein (ECP) in faecal samples from twin pairs with Crohn's disease (n = 37) or ulcerative colitis (n = 21) and from external healthy controls (n = 44). Eosinophils stained with eosinophil peroxidase (EPO) were quantified in rectal biopsies. Ratios with 95% confidence intervals were calculated.Results: Twins with Crohn' disease displayed higher levels of EDN (Ratio = 2.98, 1.65-5.37) and ECP (Ratio 1.83, 1.24-2.70) than their healthy siblings. Levels did not differ between healthy twin-siblings and external controls (EDN, Ratio = 1.52, 0.79-2.94 and ECP, Ratio = 0.93, 0.56-1.54). Higher levels of EDN (Ratio = 2.43, 1.13-5.24) and ECP (Ratio = 1.53, 0.92-2.53) were observed among twins with ulcerative colitis vs their healthy siblings. Levels did not differ between healthy twin-siblings and external controls (EDN, Ratio = 1.08, 0.51-2.25 and ECP, Ratio = 1.29, 0.74-2.26). Using intra-class correlation coefficient (ICC), we found no agreement in levels of EDN or ECP in discordant pairs, except for ECP in monozygotic Crohn's disease pairs (ICC = 0.63). In contrast, agreement was observed in monozygotic pairs concordant for Crohn's disease (EDN, ICC = 0.67 and ECP, ICC = 0.66). The number of eosinophils in rectum was increased in twins with ulcerative colitis vs their healthy sibling (Ratio = 2.22, 1.50-3.27).Conclusions: Activation of eosinophils in IBD seems to be a consequence of inflammation rather than an effect of genetic and shared environmental risk factors alone.
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| 24. |
- Salihovic, Samira, Associate Senior Lecturer, 1985-, et al.
(författare)
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Simultaneous determination of perfluoroalkyl substances and bile acids in human serum using ultra-high-performance liquid chromatography-tandem mass spectrometry
- 2020
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Ingår i: Analytical and Bioanalytical Chemistry. - : Springer. - 1618-2642 .- 1618-2650. ; 412:10, s. 2251-2259
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 25. |
- Schoultz, Ida, 1979-, et al.
(författare)
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Cellular and Molecular Therapeutic Targets in Inflammatory Bowel Disease-Focusing on Intestinal Barrier Function
- 2019
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Ingår i: Cells. - : MDPI. - 2073-4409. ; 8:2
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Forskningsöversikt (refereegranskat)abstract
- The human gut relies on several cellular and molecular mechanisms to allow for an intact and dynamical intestinal barrier. Normally, only small amounts of luminal content pass the mucosa, however, if the control is broken it can lead to enhanced passage, which might damage the mucosa, leading to pathological conditions, such as inflammatory bowel disease (IBD). It is well established that genetic, environmental, and immunological factors all contribute in the pathogenesis of IBD, and a disturbed intestinal barrier function has become a hallmark of the disease. Genetical studies support the involvement of intestinal barrier as several susceptibility genes for IBD encode proteins with key functions in gut barrier and homeostasis. IBD patients are associated with loss in bacterial diversity and shifts in the microbiota, with a possible link to local inflammation. Furthermore, alterations of immune cells and several neuro-immune signaling pathways in the lamina propria have been demonstrated. An inappropriate immune activation might lead to mucosal inflammation, with elevated secretion of pro-inflammatory cytokines that can affect the epithelium and promote a leakier barrier. This review will focus on the main cells and molecular mechanisms in IBD and how these can be targeted in order to improve intestinal barrier function and reduce inflammation.
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