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Background: Ulcerative colitis (UC), a major subtype of inflammatory bowel disease, is characterized by chronic inflammation of the colon and rectum. Enteric glial cells (EGC) play a crucial role in gut barrier maintenance and may contribute to UC pathophysiology. This study aims to investigate EGC and their associated proteins in patients during clinically active disease and in clinical remission following anti-inflammatory treatment.

Methods: Colonic or rectal biopsies were obtained at baseline from both inflamed and non-inflamed segments in 14 patients with clinically active UC initiating anti-inflammatory therapy and from the same segments when the patients were in clinical and endoscopic remission during follow-up. As control groups, colonic biopsies from 16 patients with irritable bowel syndrome (IBS)-Mixed and 16 healthy controls were included. Immunofluorescence staining assessed two EGC markers: the glial fibrillary acidic protein (GFAP+) and S100 calcium-binding protein B (S100β+). Relative estimates of inflammatory proteins in biopsies were analysed using Olink technology, In vitro, the EGC cell line CRL-2690 was exposed to interleukins (IL)-4, IL-6, and IL-18 at varying concentrations and durations, with GFAP expression analysed by western blot.

Results: In patients with UC, immunofluorescence analysis revealed significantly higher GFAP+ and S100β+ EGC counts in inflamed biopsies during active disease compared to macroscopically non-inflamed biopsies obtained during clinical and endoscopic remission. Compared to baseline biopsies from macroscopically non-inflamed mucosa, GFAP expression significantly decreased during follow-up (Figure 1), while S100β levels remained unaltered. Regardless of mucosal inflammatory status, patients with UC exhibited higher EGC counts than IBS-mixed patients and healthy controls. Our findings also showed a significant upregulation of EGC-associated pro-inflammatory proteins, such as IL-6, IL-8 and TNF in inflamed biopsies from patients with clinically active UC, compared to biopsies obtained when the patients were in remission as well as to healthy controls. Notably, these protein levels decreased during inactive UC, approaching levels observed in the healthy controls. In vitro, IL-6 upregulated GFAP expression dose- and time-dependently, while IL-4 and IL-18 induced expression in a less predictable pattern.

Conclusion: Elevated EGC counts, and pro-inflammatory proteins characterise inflamed mucosa in UC during clinical active disease highlighting their potential roles in UC related inflammation. These findings may suggest that EGC could be explored as a potential therapeutic target and may contribute to the discovery of novel biomarkers for disease monitoring.

The gut microbiota plays a pivotal role in human life and undergoes dynamic changes throughout the human lifespan, from infancy to old age. During our life, the gut microbiota influences health and disease across life stages. This review summarizes the discussions and presentations from the symposium "Gut microbiota development from infancy to old age" held in collaboration with the Journal of Internal Medicine. In early infancy, microbial colonization is shaped by factors such as mode of delivery, antibiotic exposure, and milk-feeding practices, laying the foundation for subsequent increased microbial diversity and maturation. Throughout childhood and adolescence, microbial maturation continues, influencing immune development and metabolic health. In adulthood, the gut microbiota reaches a relatively stable state, influenced by genetics, diet, and lifestyle. Notably, disruptions in gut microbiota composition have been implicated in various inflammatory diseases-including inflammatory bowel disease, Type 1 diabetes, and allergies. Furthermore, emerging evidence suggests a connection between gut dysbiosis and neurodegenerative disorders such as Alzheimer's disease. Understanding the role of the gut microbiota in disease pathogenesis across life stages provides insights into potential therapeutic interventions. Probiotics, prebiotics, and dietary modifications, as well as fecal microbiota transplantation, are being explored as promising strategies to promote a healthy gut microbiota and mitigate disease risks. This review focuses on the gut microbiota's role in infancy, adulthood, and aging, addressing its development, stability, and alterations linked to health and disease across these critical life stages. It outlines future research directions aimed at optimizing the gut microbiota composition to improve health.

BACKGROUND AND AIMS: Register-based research suggests a shared pathophysiology between inflammatory bowel disease [IBD] and spondyloarthritis [SpA], but the role of familial [genetic and environmental] factors in this shared susceptibility is largely unknown. We compared the risk of SpA in first-degree relatives [FDRs] and spouses of IBD patients with FDRs and spouses of matched population-based reference individuals.

METHODS: We identified 147,080 FDRs and 25,945 spouses of patients with incident IBD [N=39,203] during 2006-2016 and 1,453,429 FDRs and 258,098 spouses of matched reference individuals [N=390,490], by linking nationwide Swedish registers and gastrointestinal biopsy data. Study participants were followed 1987-2017. Cox regression was used to estimate hazard ratios [HRs] of SpA.

RESULTS: During follow-up, 2,430 FDRs of IBD patients [6.5/10,000 person-years] and 17,761 FDRs of reference individuals [4.8/10,000 person-years] were diagnosed with SpA, corresponding to an HR of 1.35 [95%CI:1.29,1.41]. In subgroup analyses, the increased risk of SpA was most pronounced in FDRs of Crohn's disease patients [HR=1.44; 95%CI:1.34,1.56] and of IBD patients aged <18 years at diagnosis [HR=1.46; 95%CI: 1.27,1.68]. IBD patient's spouses also had a higher SpA rate than reference individuals' spouses, but the difference was less pronounced [4.3 vs. 3.5/10,000 person-years; HR=1.22; 95%CI:1.09,1.37]. No subgroup-specific risk pattern was identified among spouses.

CONCLUSIONS: The observed shared familial risks between IBD and SpA support shared genetic factors in their pathogenesis. However, spouses of IBD patients were also at increased risk for SpA, reflecting the influence of environmental exposures or similarities in health-seeking patterns.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) has been associated with spondyloarthritis (SpA), but population-based estimates are scarce. Here we compare the occurrence of SpA before and after a diagnosis of IBD to the general population, overall and by IBD subtype and age.

METHODS: We used a nationwide register-based cohort study of 39,203 patients diagnosed with IBD during 2006-2016, identified from Swedish registers and gastrointestinal biopsy data, and 390,490 matched reference individuals from the general population. Conditional logistic regression models were used to estimate odds ratios (ORs) for a prior (prevalent) SpA diagnosis and conditional Cox regression to calculate hazard ratios (HRs) for a subsequent (incident) SpA diagnosis in IBD patients.

RESULTS: IBD patients were more likely to have prevalent SpA at IBD diagnosis (2.5%) compared to reference individuals (0.7%) with an OR of 3.48 (95%CI:3.23-3.75). They also more often received an incident diagnosis of SpA; during 23,341,934 person-years of follow-up in IBD patients, there were 1,030 SpA events (5.0/1,000 person-years) compared to 1,524 SpA events in the reference group (0.72/1,000 person-years), corresponding to an HR of 7.15 (95%CI:6.60-7.75). In subgroup analyses, associations were most pronounced among patients with Crohn's disease [(OR=5.20; 95%CI:4.59-5.89), and (HR=10.55; 95%CI:9.16-12.15)] and paediatric onset IBD [(OR=3.63; 95%CI:2.35-5.59) and (HR=15.03; 95%CI:11.01-20.53)].

CONCLUSION: IBD patients more frequently experience SpA both before and after the diagnosis of IBD compared to the general population, supporting evidence of a shared pathophysiology. The variation in SpA comorbidity across IBD subtypes and age-groups, calls for targeted approaches to facilitate timely diagnosis and intervention.

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.

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.

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.