Introduction

Environmental factors have only been partially implicated in the aetiopathogenesis of inflammatory bowel disease (IBD). The role of indoor radon, a radioactive gas, has not been formally studied and may play a role in the pathogenesis of the disease.

Aims & Methods

The aim of this study is to analyse the role of individual residential radon exposure on the incidence of IBD in a radon-prone area, also characterised as a high incidence IBD region, and whether this exposure is associated with the development of the disease.
Methods: A case-control study was developed in the health area of Santiago de Compostela (Galicia, Spain) between June 2020 and September 2023, including all consecutive incident cases with IBD. Controls were selected by frequency matching based on sex and age and without IBD. All participants had to have lived in the same home for at least 5 years. All cases were followed up for one year to assess disease progression. Endoscopic index, imaging techniques and analytical parameters were collected. In patients with IBD, hospitalisations related to the disease and the number and severity of flares (measured by Partial Mayo Score and Harvey-Bradshaw) were recorded. Radon levels measured in participants' homes over three months were compared between cases and controls, and between different types of IBD. Each individual was provided with a home radon meter (an RSKS trace detector), which was delivered and read by the Galician Radon Laboratory, a certified radon laboratory. Radon concentrations were categorised into three groups: 0-99 Bq/m3, 100-299 Bq/m3 and >299 Bq/m3. The results are expressed as odds ratios with their 95% CIs obtained by logistic regression.

Results

RADON LEVELS (Bq/m3)	IBD PATIENTS (%)	CONTROLS (%)	OR (95%CI)
0-99	34.3	19.8	1
100-299	45.2	55.8	0.5 (0.3-0.8)
>299	20.5	24.4	0.5 (0.3-0.9)

*OR = Odds Ratio; CI = Confidence Interval.
178 incident cases and 178 controls were included, with a median age of 51 years (IQR 40-59.5). 51.7% were female. 136 IBD patients completed one year of follow-up (78 ulcerative colitis, 52 Crohn's disease and 6 unclassified colitis). The median radon level in the homes of the IBD patients was 144.5 (IQR 83 - 260) and the median radon level in the homes of the controls was 189.5 (IQR 112 - 292.5). After adjustment for age and sex, high radon levels showed a negative association with the development of IBD (taking levels of 0-99 Bq/m3 as reference, OR 100-299 Bq/m3 is 0.5 (95%CI 0.3-0.8) and OR >299 Bq/m3 is 0.5 (95%CI 0.3-0.9). The results are shown in Table 1. Taking into account the different types of IBD, radon levels show the same negative association, but without statistical significance. There were no statistically significant differences in radon levels, taking levels of 0-99 Bq/m3 as reference, between hospitalised and non-hospitalised patients (OR 0.8 95%CI 0.3-2.1 for 100-299 Bq/m3, OR 1. 7 95%CI 0.6-5.0 for >299 Bq/m3), nor in patients with a flare compared with patients without a flare during the follow-up year (OR 0.4 95%CI 0.0-4.5 for 100-299 Bq/m3, OR 5.4 95%CI 0.8-34.3 for >299 Bq/m3). Radon levels were also not associated with the number of flares (OR 0.6 95%CI 0.3-1.7 for 100-299 Bq/m3, OR 1.5 95%CI 0.5-4.5 for >299 Bq/m3). Stratification by type of IBD did not alter the results.

Conclusion

High radon levels may be a protective factor against the development of IBD, and indoor radon levels do not appear to be associated with the development of IBD in terms of hospitalisations or flares.

Introduction

Inflammatory bowel diseases (IBD), encompassing ulcerative colitis (UC) and Crohn’s disease (CD), are chronic gastrointestinal disorders accompanied by psychiatric comorbidities, particularly anxiety and depression. The link between IBD and anxiety and depression remains unclear, but it appears that, among others, it may be explained by altered tryptophan metabolism. Tryptophan, an essential amino acid, is crucial for maintaining mental health and regulating mood through its metabolic processes. It serves as a precursor for several biologically significant compounds, including serotonin, melatonin, and kynurenine metabolites. The interplay between inflammation, tryptophan metabolism, and mental health in IBD remains insufficiently explored.

Aims & Methods

This study aimed to assess the association between metabolites of the tryptophan-kynurenine pathway and depressive symptoms in IBD regarding the disease activity and phenotype. A cohort of 214 patients with IBD (70 with CD and 144 with UC) was included. Disease activity was determined using the Mayo score for UC and SES-CD for CD. Peripheral blood samples were analyzed for selected biomarkers, including metabolites of tryptophan-kynurenine pathway as well as indicators of oxidative stress and inflammation. Depressive symptoms were evaluated using the Beck Depression Inventory (BDI). Statistical analyses included correlation and regression models to explore the relationship between biomarkers and BDI scores, adjusting for clinical and demographic covariates.

Results

The BDI score in the study group ranged from 0 to 52. 31 individuals met the criteria for depression by scoring over 10 points. 137 patients with active disease exhibited significantly higher levels of hsCRP and nitrotyrosine and lower kynurenic acid levels compared to 77 with inactive disease. Kynurenic acid levels were negatively correlated with BDI scores (r = -0.220, p = 0.042), suggesting an association between tryptophan metabolism and depressive symptoms. Additionally, CD patients showed higher serotonin and anthranilic acid levels compared to UC patients (16.67 ± 26.23 vs 6.29 ± 12.55 and 0.35 ± 0.26 vs 0.17 ± 0.17, respectively), though no significant differences in BDI scores were observed between the groups. Biological treatment was more frequent in the active disease group and associated with higher BDI scores, even after adjusting for covariates.

Table 1. Comparison of selected metabolite levels between individuals with active disease and with inactive disease

	Active disease	Inactive disease	p
Chlorotyrosine, nM	0.35 ± 0.41	0.26 ± 0.45	0.222
Nitrotyrosine, nM	0.38 ± 0.20	0.26 ± 0.17	0.043
Bromotyrosine, nM	0.05 ± 0.06	0.03 ± 0.03	0.553
L-tryptophan, M	54.67 ± 15.79	60.98 ± 15.34	0.117
L-kynurenine, M	3.53 ± 1.22	3.48 ± 1.01	0.680
5-hydroxy-L-trypthophan, M	0.20 ± 0.15	0.23 ± 0.13	0.233
3-indolepropionic acid, M	0.33 ± 0.57	0.20 ± 0.21	0.723
3-indoleacyrylic acid, M	2.31 ± 0.66	2.46 ± 0.54	0.322
Kynurenic acid, M	0.06 ± 0.04	0.08 ± 0.03	0.035

Data expressed as n (%) or mean ± SD.
Significant between-group differences (p < 0.05) are marked in bold.

Conclusion

The study revealed significant differences in the tryptophan-kynurenine metabolic pathway among patients with inflammatory bowel disease, which vary based on disease activity. Additionally, variations in the concentrations of certain metabolites are correlated with the severity of depression.

References

1. Kuźnicki, P., Kempiński, R., & Neubauer, K. (2021). The emerging role of mood disorders in inflammatory bowel diseases. In Advances in Clinical and Experimental Medicine. https://doi.org/10.17219/ACEM/127676
2. Mikocka-Walus, A., Pittet, V., Rossel, J.-B., von Känel, R., Anderegg, C., Bauerfeind, P., Beglinger, C., Begré, S., Belli, D., Bengoa, J. M., Biedermann, L., Bigler, B., Binek, J., Blattmann, M., Boehm, S., Borovicka, J., Braegger, C. P., Brunner, N., Bühr, P., … Zimmermann, D. (2016). Symptoms of Depression and Anxiety Are Independently Associated With Clinical Recurrence of Inflammatory Bowel Disease. Clinical Gastroenterology and Hepatology, 14(6), 829-835.e1. https://doi.org/10.1016/j.cgh.2015.12.045
3. Brown, S. J., Huang, X.-F., & Newell, K. A. (2021). The kynurenine pathway in major depression: What we know and where to next. Neuroscience & Biobehavioral Reviews, 127, 917–927. https://doi.org/10.1016/j.neubiorev.2021.05.018
4. Correia, A. S., & Vale, N. (2022). Tryptophan Metabolism in Depression: A Narrative Review with a Focus on Serotonin and Kynurenine Pathways. International Journal of Molecular Sciences, 23(15), 8493. https://doi.org/10.3390/ijms23158493

Introduction

Inflammatory bowel disease (IBD) is a chronic multi-factorial disease characterized by inflammation of the gastrointestinal tract. Currently, the mechanisms underlying the disease are far from being elucidated. Thus, the study of proteins involved in its pathogenesis would allow further insights into the molecular mechanisms underlying IBD.

Aims & Methods

The serum and intestinal mucosa (ileum and left colon) proteomic profiles of patients with Crohn´s disease (CD) and ulcerative colitis (UC) and healthy controls (HC) were analyzed through label-free relative quantitative proteomic profiling using nLC MS/MS. Data mining and pattern recognition techniques were performed to identify hidden relationships that are not detectable using classical linear classifiers, and thus identify potential markers able to discriminate between the different study groups. Six candidate biomarkers were selected for further validation using enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) in serum and intestinal tissue samples, respectively.

Results

Comparison of serum proteins between UC patients and HC revealed statistically lower levels of protein 1 and 2 and higher levels of protein 3. The comparison of potential biomarkers between CD and HC group showed lower levels of protein 1 and higher levels of protein 3. In addition, protein 4 was differentially upregulated in CD patients compared to UC. Regarding the intestinal biopsies, protein 5 showed higher intensity in the IHC staining of ileum from CD patients compared to HC, whereas protein 6 was significantly decreased in left colon and ileum from CD and UC patients compared to HC. These proteins are involved in thyroxine transport, regulation of chemotactic chemokine activity, inflammatory processes, triglyceride homeostasis, oxidative stress and regulation of NF-kappa-B activation in the cytosol.

Conclusion

In this study, we have identified a panel of six potential biomarkers that could help to elucidate mechanisms involved in IBD pathogenesis. Their roles in the pathophysiology need to be clarified in further experiments.

Introduction

Chronic inflammatory bowel diseases (IBD), such as Crohn's disease and ulcerative colitis, are associated with an increased risk of various cancers, particularly colorectal cancer, but also other types, such as small intestine, biliary tract, or liver cancers. Additionally, certain extra-digestive cancers may also occur in patients with these conditions. These risks vary depending on the duration and severity of inflammation, as well as other factors such as family history or exposure to certain treatments. This work explores the diversity of cancers associated with IBD, their prevalence, and their clinical characteristics, highlighting the importance of considering these risks in the medical management of patients.

Aims & Methods

This is a retrospective and descriptive single-center study conducted within a hepatogastroenterology department, focusing on patients followed for inflammatory bowel diseases (IBD) who developed cancer. The study covers the period from 1990 to 2025.

Results

Out of a total of 1,795 patients followed for IBD (1,200 for Crohn's disease and 595 for ulcerative colitis), 2% (36 patients) developed cancer. The male-to-female sex ratio was 0.38, with a clear female predominance. Among the patients, 69.4% (25) had Crohn's disease, and 30.55% (11) had ulcerative colitis.
The most common location of Crohn's disease was colonic involvement (44%, 11 cases),the predominant phenotype was inflammatory (52%, 13 cases) ,for ulcerative colitis the most frequent location was left-sided colitis (54%, 6 cases) ,the median disease duration before the onset of cancer was 60 months.
Digestive cancers were the most commonly associated with IBD (38.8%, 14 cases), followed by breast cancer in women (30.5%, 11 cases), gynecological cancers (11.1%, 4 cases), prostate adenocarcinoma (5%, 2 cases), skin cancers (5%, 2 cases), and other cancers (5%, 2 cases).
Only 30.5% (11 patients) had risk factors (chronic smoking, family history of cancer, etc.).
Regarding treatment, 33% (12 patients) were on biologic therapy , 30.5% (11) were on azathioprin , 16.6% (6) were on therapeutic abstention , 8.3% (3) were on aminosalicylates, and 5.5% (2) were on corticosteroids.
Treatment was discontinued in 63.8% (23) of patients after the discovery of cancer, and 22% (8) experienced a flare-up which was successfully managed with corticosteroid therapy.
Eighty-three point three percent (83.3%, 30 patients) underwent surgical treatment alone or in combination with radiochemotherapy. Sixteen point six percent (16.6%, 6 patients) were at an advanced stage and had metastases, so they received palliative treatment.
Thirty-six percent (36%, 13 patients) had a good outcome, 30.5% (11) were lost to follow-up, and 2.7% (1) died.

Conclusion

The study shows a 2% cancer incidence in IBD patients, slightly higher than the general population's risk (0.3–0.5% annually), likely due to prolonged inflammation and disease duration. These findings highlight the need for enhanced cancer surveillance and preventive strategies, especially for patients with colonic involvement.

Introduction

Apelin, an adipokine secreted from visceral fat, has been associated with endothelial cells dysfunction‐related chronic inflammatory diseases. Decreased serum apelin levels have been found in patients with cardiovascular disease (CVD). Higher apelin levels have been measured in mesenteric adipose tissue and inflamed colonic epithelium of patients with Inflammatory Bowel Disease (IBD), but data on the role of serum apelin levels in IBD patients are lacking.

Aims & Methods

We aimed to a) compare serum apelin levels between 104 consecutive IBD patients and 104 age and sex matched healthy controls (blood donors), b) to evaluate the correlation between serum apelin levels with demographics, disease characteristics, treatment and disease course.
Serum apelin-13 levels were measured using ELISA (Wuhan Fine Biological Technology Co., Ltd). Statistical analysis was performed with SPSS 24 (SPSSInc. Chicago, IL, USA).

Results

Mean apelin levels were significantly higher in IBD patients compared to their matched healthy controls (1996.29 ± 1592.96pg/ml vs 1552.99 ± 809.64, p=0.012). Among the examined parameters only smoking was found independently associated with serum apelin levels in IBD patients (p<0.001).
IBD patients with CVD (25) had lower but not significant different serum apelin levels compared to patients without CVD (79) (1743.01 ± 1116.26pg/dl vs 2465.09 ± 2006.51pg/ml, p=0.122). In a subgroup analysis of patients without CVD (79 IBD patients) significantly elevated serum apelin levels were found in patients with extended UC, history of immunomodulator use and absence of musculoskeletal EIMs (2539,69 ± 1969.29pg/ml vs 1164.45 ± 818.89pg/ml, p=0.044, 2317.69 ± 1867.99pg/ml vs 1451.40 ± 1024.20pg/ml, p=0.043 and 2340.58 ± 1850.16pg/ml vs 1392.09 ± 1054.99pg/ml, p=0.027, respectively).
Finally, a moderate positive correlation was found among UC extent and serum apelin levels in patients without CVD (r=0.525, p=0.004). Νegative correlations were found among age at study entry and serum apelin levels in both IBD patients without CVD and all IBD patients (r=-0.263, p=0.001 and r=-0.214, p=0.002, respectively) and between immunomodulator use, history of musculoskeletal EIMs and serum apelin levels in patients without CVD (r=-0.26, p=0.021 and r=-0.336, p=0.005, respectively).

Conclusion

The circulating serum apelin levels are significantly increased in IBD patients compared to matched healthy controls. Increased apelin levels are independently associated with smoking status and disease extend (in UC). IBD patients with musculoskeletal manifestations have decreased serum apelin levels compared to IBD patients without musculoskeletal manifestations. Further investigation with larger studies on the role of serum apelin in IBD is needed.

Disclosure

None