Introduction

The role of adipose tissue in IBD is yet to be fully elucidated. Adipose tissue is distributed into two main compartments ; Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Previous studies suggest that VAT may be a predictor of disease progression particularly in Crohn’s disease (CD)(1). VAT:SAT ratio, and not BMI, has been associated with a structuring CD phenotype, faecal calprotectin and quality of life (2). In previous studies, visceral obesity has been defined as a VAT area of 100cm² as well as VAT:SAT 40% (3-4). We sought to investigate the difference in fat composition of patients with IBD using computed tomography (CT).

Aims & Methods

Patients with IBD were selected randomly from an IBD database in our centre. Age and gender matched controls were selected for comparison.
Using TeraRecon^​ software, we retrospectively analyzed CT results to obtain the following parameters; VAT Area (cm²), SAT Area (cm²), VAT:SAT Ratio (VAT/VAT+SAT - %) and Waist Circumference (WC) (cm). Measurements were taken at the level of the umbilicus (L3). Data was also collected retrospectively from outpatient clinic letters, previous biopsy reports and endoscopy reports. Statistical analysis was preformed using Minitab.

Results

A random sample of 480 patients were identified. 279 of these patients were excluded, leaving 201 patients which were analysed.
The majority of this cohort were female (n=102). The mean age was 43. 122 patients had CD and 79 patients had Ulcerative colitis (UC). At the time of imaging, 95 patients were on biologics with a further 29 patients progressing onto biologics later in their treatment. Visceral obesity (40% VAT:SAT) was found in 31.8% of patients. 46.8% of patients had VAT 100cm². Male gender accounted for 17.27% more VAT:SAT in comparison to female gender (p =0.000). VAT showed a strong correlation with WC (r =0.809).
No significant difference was found in fat composition or WC between a sample of patients with IBD and their controls.
Patients with UC had 5.2% more VAT:SAT compared to patients with CD (p=0.036). Males had a 17.3% higher VAT:SAT (p=0.000). There was no significant differences noted between those on biologics vs. non-biologic treatments. However, those taking thiopurines (6-Mercaptopurine (6-MP)/Azathioprine) had 5.6% lower VAT:SAT compared to those not (p=0.038). Combination therapy (thiopurine + Biologic) had 9.02% more VAT:SAT than those on thiopurine monotherapy (p=0.058).
Binary logistic regression models were used to identify factors associated with markers of disease severity (surgery, multiple surgeries and multiple biologic use). Age was found to be a significant associated factor with multiple surgeries (coeff 0.0641) (p=0.001).

Conclusion

Visceral obesity was found in at least 30% of patients in this IBD cohort. This was in comparison to 44%of the age-gender matched control group.
We report no significant difference in body fat composition or WC in age and gender matched controls and a random sample of patients with IBD. Rising obesity levels in the community may account for this. However, in this cohort, patients with UC had a higher % VAT:SAT compared to those with CD. Regarding treatment, thiopurine monotherapy was associated with lower %VAT:SAT. This may suggest that combination therapy may be required in those with higher %VAT:SAT to treat a more aggressive disease course.
Age is a known risk factor for a more severe disease course in IBD. This was in keeping with our model.
Of note, WC showed a strong correlation with VAT. This may be a more acceptable alternative for monitoring VAT rather than CT imaging.

References

1. Tsai, Y.-W. et al. (2020) “Adipokine-modulated immunological homeostasis shapes the pathophysiology of inflammatory bowel disease,” International Journal of Molecular Sciences, 21(24), p. 9564. Available at:https://doi.org/10.3390/ijms21249564.
2. Bryant, R.V. et al. (2018) “Visceral adipose tissue is associated with stricturing crohn’s disease behavior, fecal calprotectin, and quality of life,” Inflammatory Bowel Diseases, 25(3), pp. 592–600. Available at: https://doi.org/10.1093/ibd/izy278.
3. Kong, M. et al. (2022) “Assessing visceral obesity and abdominal adipose tissue distribution in healthy populations based on computed tomography: A large multicenter cross-sectional study,” Frontiers in Nutrition, 9. Available at: https://doi.org/10.3389/fnut.2022.871697.
4. Matsuzawa, Y. et al. (1995) “Visceral fat accumulation and cardiovascular disease,” Obesity Research, 3(S5). Available at: https://doi.org/10.1002/j.1550-8528.1995.tb00481.x.

Introduction

Patients diagnosed with inflammatory bowel disease (IBD) may have damage in different parts of the gut. The development of this disease involves an intricate interaction between a host with genetic susceptibility, environmental factors, an imbalanced immune response, and intestinal microbiota. Several studies have revealed discrepancies in the composition of gut microbiota between IBD patients and healthy individuals, especially concerning microbial diversity and relative abundance of specific bacteria. Nonetheless, previous research typically involves patients who have undergone immunosuppressive treatment, potentially altering the microbiota and affecting the integrity of study findings.

Aims & Methods

The aim of this study was to elucidate the differences in the microbiota of newly diagnosed patients with Crohn’s disease (CD) and ulcerative colitis (UC) compared to healthy controls (HC), based on the location of the affected area. Stool samples were obtained from IBD patients who had not yet initiated treatment for the disease, and from HC. Each sample underwent shotgun metagenomic sequencing, followed by bioinformatic analysis using the Cutadapt, Kraken2, and Bracken programs. Shannon index (α-diversity) and Bray-Curtis dissimilarity (β-diversity) were used as tests of within-species diversity and within-group diversity, respectively.

Results

We included 103 patients with CD, 144 with UC and 49 HC. Patients with CD, which have been classified depending on disease location (ileal, colonic and ileocolonic), showed lower α-diversity compared to HC in each subgroup, showing the lowest index in those with ileocolonic location. In UC patients, divided according to disease extension (proctitis, left-sided colitis and extensive colitis), those with extensive involvement, exhibited the lowest α-diversity compared to HC and other groups. β-diversity in CD patients revealed the highest differences between the comparisons ileal vs ileocolonic and colonic vs ileocolonic, suggesting that patients with ileocolonic pattern showed a more different microbiota profile compared to the other groups studied; however, there were no differences in UC patients. Examination of taxonomic abundance revealed a decrease in Phocaeicola coprocola and several species of Adlercreutzia, and an increase in Shigella flexneri, in CD patients, compared to HC. In UC patients, an increase in Toxoplasma gondii and Gemella morbillorum was observed in all three extension subgroups compared to HC. However, several species of Adlercreutzia and Alistipes were decreased in patients with extensive colitis compared to HC.

Conclusion

Our data suggest that newly diagnosed CD and UC patients showed relevant differences in the microbiota depending on the location of the disease, with a reduction in beneficial genus such as Adlercreutzia and Alistipes, and an increase in pathogenic species.

Introduction

Histologic activity has emerged as an aspirational therapeutic goal in IBD management. It is not yet a formal treatment-target in either CD or UC. However, it could be used as an adjunct to mucosal healing to represent a deeper level of healing. Recent studies show that histologic healing is associated with decreased risk of clinical relapse, medication escalation and corticosteroid use, both in ulcerative colitis and Crohn's disease [1,2]. We investigated histologic remission (HR) rates and potential predictors of achieving histologic remission in an IBD cohort.

Aims & Methods

We conducted a retrospective subgroup analysis of data collected from IBD patients enrolled in an ongoing prospective cohort study. Clinical, biological, endoscopic data (including the Mayo endoscopic subscore and SES-CD score) and histopathology results were available at multiple time-points for the enrolled patients (annual visits). Mucosal healing was defined as SES-CD <3 or Mayo endoscopic score=0[3]. Histologic healing was defined as microscopic normalization of mucosal biopsies.

Results

219 patients (88 CD, 131 UC) were enrolled in our study and were prospectively followed for a median length of 2 years (range 0-5 years), totaling 452 study visits. Mucosal healing was recorded for 51 (27 UC, 24 CD, 23,2%) patients at 76(16%) different study visits. Overall, only 35(15%) patients achieved histologic healing. In the mucosal healing subgroup, histologic remission was achieved in 30(58%) patients. After logistic regression analysis, none of the investigated factors was associated with histologic remission.

Conclusion

Mucosal healing and endoscopic remission rates are low in real-life settings. Frequently used patient and disease related factors, including mucosal healing are not reliable predictors for histologic remission.

References

[1] Christensen B, Erlich J, Gibson PR, Turner JR, Hart J, Rubin DT. Histologic Healing Is More Strongly Associated with Clinical Outcomes in Ileal Crohn's Disease than Endoscopic Healing. Clin Gastroenterol Hepatol. 2020 Oct;18(11):2518-2525.e1. doi: 10.1016/j.cgh.2019.11.056. Epub 2019 Dec 5.
[2]Battat R, Duijvestein M, Guizzetti L, Choudhary D, Boland BS, Dulai PS, Parker CE, Nguyen TM, Singh S, Vande Casteele N, Pai RK, Feagan BG, Sandborn WJ, Jairath V. Histologic Healing Rates of Medical Therapies for Ulcerative Colitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Am J Gastroenterol. 2019 May;114(5):733-745. doi: 10.14309/ajg.0000000000000111.
[3] Turner D, Ricciuto A, Lewis A, D'Amico F, Dhaliwal J, Griffiths AM, Bettenworth D, Sandborn WJ, Sands BE, Reinisch W, Schölmerich J, Bemelman W, Danese S, Mary JY, Rubin D, Colombel JF, Peyrin-Biroulet L, Dotan I, Abreu MT, Dignass A; International Organization for the Study of IBD. STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD. Gastroenterology. 2021 Apr;160(5):1570-1583. doi: 10.1053/j.gastro.2020.12.031. Epub 2021 Feb 19. PMID: 33359090.

Introduction

Therapeutic goals in inflammatory bowel diseases (IBD) have undergone considerable change in recent years, with a shift of focus from simply achieving clinical remission. Patient-related outcomes (PROs) have also become increasingly important as adjunctive tools in assessing the efficacy of medical therapy from the patients’ standpoint. Health-related quality of life (HRQoL) questionnaires, correlate well with disease activity and can detect meaningful clinical changes in IBD patients who either suffer a relapse of disease or achieve remission [1,2].

Aims & Methods

We aimed to assess the utility of SIBDQ in the long-term follow-up of IBD patients compared to the conventionally used markers such as clinical indices, CRP levels and endoscopic activity scores. Patients were scheduled for evaluation every 12 months, but additional evaluations were performed as required in case of worsening clinical condition. The main data collected at each study visit included clinical aspects (disease activity, on-going medication, quality of life assessement-The Short Inflammatory Bowel Disease Questionnaire), endoscopic and histological findings.

Results

In a prospective setting, 176 patients were included in the study (65 Crohn’s and 111 UC patients) , with a mean follow-up time of 16 months and 1.3 study visits per patient. Clinical activity was associated with significantly lower SIBDQ (median 4.3 vs 5.7 in those without clinical activity, p<0.001 mann whitney u) and increased inflammatory burden ( median CRP levels 1,99 mg/L vs. 7.2mg/L, p<0.001 mann whitney u). SIBDQ scores were also significantly higher in patients showing mucosal healing compared to those with active ongoing inflammation (5.8 vs 4.9, p<0.001 MWU), while inflammatory burden was also significantly different between patients with and without ongoing mucosal activity (1.6 mg/L vs 4.2 mg/L, p< 0.001 MWU). SIBDQ significantly improved over time, with a median of 4.7, 5.4 and 5.8 at visits 1, 2 and 3 respectively (p<0.001 MWU), which was also consistent with a decrease in the overall inflammatory burden in the cohort (median CRP levels of 4.2, 3.4 and 2.5 mg/L respectively).

Conclusion

Clinical activity is associated with significantly lower quality of life and increased inflammatory burden. QoL scores are significantly higher in patients showing mucosal healing compared to those with active ongoing inflammation.

References

[1] Jowett SL, Seal CJ, Barton JR, Welfare MR. The short inflammatory bowel disease questionnaire is reliable and responsive to clinically important change in ulcerative colitis. Am J Gastroenterol. 2001 Oct;96(10):2921-8.
[2] Irvine EJ^​, Zhou Q, Thompson AK.The Short Inflammatory Bowel Disease Questionnaire: a quality of life instrument for community physicians managing inflammatory bowel disease. CCRPT Investigators. Canadian Crohn's Relapse Prevention Trial. Am J Gastroenterol. 1996 Aug;91(8):1571-8.

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

Introduction

Inflammatory bowel disease (IBD) is strongly associated with joint inflammation, as is highlighted by the high prevalence of spondyloarthritis (SpA) in patients with IBD (up to 13%) compared to the general population (0.2-1.6%) [1, 2]. IBD and SpA have many overlapping features, including genetic risk factors, changes in the gut microbiota, and therapies targeting TNF-α , IL-23, or JAK [3]. However, current therapies for both diseases are unable to break the cycle of chronic inflammation, and still a significant proportion of patients fail to respond. Disease heterogeneity likely plays a role in this [4, 5], underscoring the necessity to improve management and refine classification.

Aims & Methods

In this study, 92 inflammation-related proteins were quantified in serum of patients from one IBD and one SpA cohort using the novel Olink proteomics proximity extension assay. Fold changes (FC) in expression with |log₂FC| > 0.5 were considered meaningful, and false discovery rates (FDR) <0.05 were considered significant. The IBD cohort existed of 255 IBD patients with (n=155) and without (n=100) self-reported joint complaints [8]. From the patients with joint complaints, 58 fulfilled any of the SpA criteria. The SpA cohort, or SPACE cohort, consisted of 169 patients with chronic back pain (≥3 months, ≤2 years) of unknown origin [9]. After 2 years of follow-up, 85 patients had proven axSpA. Serum samples were taken at baseline, and 167/169 samples from the SPACE cohort and 241/255 samples from the IBD cohort passed quality control and were included in the analysis.

Results

Thirty-four proteins were differentially expressed between 95 IBD patients without joint complaints and 85 proven axial SpA (axSpA) patients from the SPACE cohort, of which 14 were higher in IBD patients (including 4E‑BP1, IFN‑γ, TNF, FGF‑21, CD8A, and CCL9), and 20 were higher in axSpA patients (including CASP‑8, SIRT2, STAMBP, FGF‑19, ST1A1, and EN‑RAGE). In addition, the immune profile of IBD patients with joint complaints differed from IBD patients without joint complaints: 4E‑BP1, CASP-8, STAMBP, SIRT2, AXIN1, and TNFSF14, were significantly upregulated in patients with joint complaints. Of note, if IBD patients without joint complaints were compared to the subgroup of 58 patients with joint complaints who met criteria for SpA, the same proteins showed significant upregulation, suggesting minimal difference between IBD patients with joint complaints who meet or who do not meet SpA criteria. Direct comparison of patients who met and who did not meet SpA criteria within the group of IBD patients with joint complaints indeed showed no noteworthy difference in serum immune profile. Within the SPACE cohort, comparison of patients with chronic back pain with and without axSpA diagnosis also showed no significant difference in serum protein expression.

Conclusion

This study shows that patients with axSpA versus patients with IBD without joint complaints have differing serum immune profiles. Within IBD patients with self-reported joint complaints and within patients with self-reported chronic back pain (from the SPACE cohort), no distinct difference in immune profile is observed, regardless of SpA diagnosis. The inflammation signatures of patients with chronic inflammatory diseases should be further investigated to provide insights for enhancing disease management in the future.

References

1. Karreman, M.C., et al., The Prevalence and Incidence of Axial and Peripheral Spondyloarthritis in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis. J Crohns Colitis, 2017. 11(5): p. 631-642.
2. Stolwijk, C., et al., Global Prevalence of Spondyloarthritis: A Systematic Review and Meta-Regression Analysis. Arthritis Care Res (Hoboken), 2016. 68(9): p. 1320-31.
3. Gracey, E., et al., Revisiting the gut-joint axis: links between gut inflammation and spondyloarthritis. Nat Rev Rheumatol, 2020. 16(8): p. 415-433.
4. van Unen, V., et al., Mass Cytometry of the Human Mucosal Immune System Identifies Tissue- and Disease-Associated Immune Subsets. Immunity, 2016. 44(5): p. 1227-39.
5. Gulino, G.R., M. Van Mechelen, and R. Lories, Cellular and molecular diversity in spondyloarthritis. Semin Immunol, 2021. 58: p. 101521.
6. van Erp, S.J., et al., Classifying Back Pain and Peripheral Joint Complaints in Inflammatory Bowel Disease Patients: A Prospective Longitudinal Follow-up Study. J Crohns Colitis, 2016. 10(2): p. 166-75.
7. Marques, M.L., et al., Can rheumatologists unequivocally diagnose axial spondyloarthritis in patients with chronic back pain of less than 2 years duration? Primary outcome of the 2-year SPondyloArthritis Caught Early (SPACE) cohort. Ann Rheum Dis, 2024. 83(5): p. 589-598.

Disclosure

FAG: grants from Stichting vrienden van Sole Mio and Stichting ASAS, grants and/or consulting fees from Abbvie, ASAS, BMS, Galapagos, Janssen, Lilly, Novartis, Pfizer, and UCB.
AEM: grants from Nestle, Norgine, Cablon, Galapagos, and ZonMW, ad boards/speaker fees from Tramedico, Janssen, Takeda, Galapagos, Vedanta, Ferring, AbbVie, and Dear Health.
PV: speaker fees from Takeda and Galapagos, advisory board: Takeda, Galapagos, Lilly, BMS, Janssen, and Abbvie

Introduction

Inflammatory bowel disease (IBD) and atopic diseases, namely asthma, atopic dermatitis (AD), and atopic rhinoconjunctivitis (AR) show a rising prevalence worldwide and share some genetic and epidemiological risk factors. Consequently, observational studies have explored the potential association between IBD and atopic diseases, with some conflicting data.

Aims & Methods

The objective of this study was to systematically review and summarize the current evidence on the co-occurrence of IBD and these atopic diseases.
We searched Medline, Embase, Web of Science and CENTRAL (from inception to August 14, 2022) to identify observational studies on the incidence or prevalence of IBD in atopic diseases (asthma, AD; AR) and vice versa.

Results

We included 23 observational studies (17 cohort, 4 case-control, 2 cross-sectional) on the association between IBD and asthma, comprising approximately 2 million patients; 17 of them showed a positive association and only one study showed a negative association. Nineteen studies (12 cohort, case-controls, 4 cross-sectional) on the association between IBD and AD were included, with approximately 2,6 million patients; 16 showed a positive association and 3 showed no association. We included 4 cohort studies on the association between IBD and AR, covering approximately 2,2 million patients which all showed a positive statistically significant association.

Conclusion

Published literature supports that IBD is associated with asthma, AD and AR, and vice versa. These results may increase gastroenterologists’ awareness for these diagnoses so that timely management can be initiated. Additional research is needed to determine if one disease influences the risk of developing the other or if the frequent co-occurrence of these diseases results from shared genetic, environmental and microbial factors. As far as the author’s know, this is the first systematic review that reports the association between IBD and the three main atopic diseases.