Exabis Library

Summary of the talk

Timely limitation of the inflammatory process is essential, because its self-perpetuation will otherwise lead to the onset of complications and disease progression. In contrast to inflammatory processes, resolution of inflammation and molecular healing are far less well understood in IBD. In-depth characterization of pathways that terminate inflammation and lead to molecular healing has been incomplete to date. Resolution of inflammation involves several active processes rather than just a stepwise clearance of pro-inflammatory mediators. Recent studies have shown that blockade of just one of the pro-inflammatory mediators might be circumvented by the activation of alternative, redundant pro-inflammatory pathways, thus leading to loss of response. An improved understanding of these resistance mechanisms would help us to improve our currently used therapeutic strategies and reveal new treatment targets and concepts. Our future therapeutic aim should be the restoration of mucosal homeostasis and resolution of all perturbed molecular components (e.g. activation of immune cells, perturbed epithelial barrier integrity and disturbed antigen tolerance). This kind of molecular healing might minimize the risk for relapses and lead to lasting control of the disease.

1.)    To understand mechanisms that are involved in the resolution of inflammation and molecular healing in IBD

2.)    To get an overview on identified molecular resistance mechanisms to biological therapies and how they could be therapeutically utilized

3.)    To understand how molecular healing could be defined in IBD

Dr Alka Potdar and Dr Janine Bilsborough discuss their paper analysing genetic and transcriptomic sub-classifiers of small bowel Crohn’s and the associated phenotypic characteristics.

https://academic.oup.com/ecco-jcc/pages/podcast 

Some genetic polymorphisms (present in less than 30% of patients) and environmental factors, such as tobacco exposure, have been identified to increase the susceptibility for developing inflammatory bowel disease (IBD), but it is suspected that there may be other still unknown environmental or epidemiological factors. In this sense, some studies suggested an increased incidence of IBD in individuals undergoing bariatric surgery (BS) for morbid obesity (MO). We aimed to assess whether BS or MO are associated with an increased risk of developing IBD.

All individuals resident in Catalonia (7.7 million inhabitants in 2021) with a diagnosis of obesity or MO within the period 2005-2020 were identified from the Catalan Public Health System Database. Children under the age of 18 and those diagnosed with IBD prior to the diagnosis of obesity or MO were excluded. Individuals BS and those with a new diagnosis of IBD were identified, and the likelihood of developing IBD was analyzed by Kaplan-Meier survival analysis. A Cox regression multivariable analysis was performed to assess independent risk factors for the development of IBD, Crohn’s disease (CD) and ulcerative colitis (UC).

Three cohorts were identified: 94,473 individuals with MO; 1,009,256 with obesity; and 14,698 who underwent BS during the study period. A total of 4,277 new diagnoses of IBD were identified, of which 78 among individuals who underwent BS prior to IBD diagnosis (0.84 cases per 1000 person-years), 409 among individuals with OM but without BS (0.90 cases per 1000 person-years), and 3,790 in obese individuals (0.60 cases per 1000 person-years). The likelihood of developing IBD was significantly higher in patients with MO as compared with obese patients (HR 1.46; 95%CI 1.32-1.62). These differences were maintained when the likelihood of developing CD or UC were assessed separately. In the multivariable logistic regression analysis, MO (HR 1,68; CI95% 1.41-1.99), female gender (HR 1.17; 95%CI 1.05-1.31) and active smoking (HR 1.62; 95%CI 1.43-1.84) were associated with an increased risk of CD. In UC, MO (HR 1,36; 95%CI 1.19-1.55) and BS (HR 2.62; 95%CI 1.34-2.11) were independent risk factors, whereas female gender (HR 0.86; 95%CI 0.79-0.93) was an independent protective factor.

MO is an independent risk factor for the development of IBD, for both CD and UC, whereas BS seems to increase the risk only for UC.

Educational Objectives:

1. Reminder: why nutrition in IBD?
2. How to best deliver nutritional care in IBD: MDT
3. Seeing this through the lens of an adult IBD dietitian
4. Lessons learned from treating adults/elderly with IBD
5. Psychological challenged with nutritional therapy
6. MDT from both our points of view
7. D-ECCO – who we are and what’s in it for you?
    

Summary:

As PIBD specialists we are all aware of the importance and potential of nutritional therapy in IBD, but how is this best delivered?

This presentation, by a dietitian and physician, who are members of the Dietitians of ECCO (D-ECCO) committee, will include our views and experience with managing nutrition in IBD, through a multidisciplinary team. We will mention how to advocate and setup a successful team and highlight some specific settings where an MDT is especially critical, such as peri-surgical care. Lessons learned from treating the elderly IBD population, and the interesting parallels to paediatrics, will be discussed. Finally, we will explain why and how you should get your team involved in D-ECCO activities.

Although respiratory failure is the hallmark of severe disease, it is increasingly clear that Coronavirus Disease 2019 (COVID-19) is a multi-system disorder. The presence of gastrointestinal (Gl) involvement by Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been suggested by epidemiological, clinical, non-human primate, in-vitro (enteroid) and ex-vivo (human biopsy) studies. Having recently documented persistence of SAR-CoV-2 within the intestinal epithelium 7 months after infection, here we aimed to study mucosal immune cell abnormalities in individuals with prior history of COVID-19.

Individuals with previous COVID-19 diagnosis (by either RT–PCR or seroconversion) and controls (without RT-PCR or serological evidence of prior COVID-19 infection) undergoing endoscopic evaluation were recruited into the study (Table 1,2). Colonic and small intestinal (duodenal and ileal) biopsies were analyzed by multiparameter flow cytometry for mucosal immune cell populations including myeloid cells (classical and non-classical monocytes, dendritic cell subsets), T cells (subsets and activation state), B cells (including plasma cells). Persistence of viral antigens was determined by immunofluorescence microscopy (n=30) using a previously published anti-nucleocapsid (NP) antibody.

Thirty subjects with a previous history of COVID-19 (post-COVID), median of 4 months from diagnosis (range 1-10 months), were recruited and compared with 40 normal volunteer (NV) controls. Relative to controls, post-COVID subjects displayed higher frequencies of classical (CD14⁺) monocytes in both, the colon and the small bowel, while significantly higher frequencies of conventional dendritic cells (cDC) 1 (lin^-HLA-DR^hiCD14^-CD11c⁺CD141⁺) and cDC2 (lin-HLA^-DR^hiCD14^--CD11c⁺CD1c⁺) were noted in the colon only. Among T cell subsets, CD8⁺ tissue resident memory T cells (CD8⁺CD69⁺CD103⁺) were significantly increased in colon of post-COVID subjects compared to NV. Among B cell subsets, plasma cells (CD3^-CD27⁺CD38^hi) trended higher (p=0.06), while mucosal B cells (CD3^-CD19⁺) were significantly lower in the terminal ileum of post-COVID subjects compared to NV. Finally, with IF, we detected SARS-CoV-2 NP in 10 out of 30 (33%) of post-COVID subjects (Figure 1).  There were no significant correlations of these cell populations with either time after the infection or IF positivity.

Innate and adaptive immune cell abnormalities persist in the intestinal mucosa of post-COVID subjects for up to 10 months and may reflect viral persistence or immune cell dysregulation in the intestines. These findings have major implications for understanding the pathogenesis of long term sequela of COVID-19, including long-haul COVID. 

Although respiratory failure is the hallmark of severe disease, it is increasingly clear that Coronavirus Disease 2019 (COVID-19) is a multi-system disorder. The presence of gastrointestinal (Gl) involvement by Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been suggested by epidemiological, clinical, non-human primate, in-vitro (enteroid) and ex-vivo (human biopsy) studies. Having recently documented persistence of SAR-CoV-2 within the intestinal epithelium 7 months after infection, here we aimed to study mucosal immune cell abnormalities in individuals with prior history of COVID-19.

Individuals with previous COVID-19 diagnosis (by either RT–PCR or seroconversion) and controls (without RT-PCR or serological evidence of prior COVID-19 infection) undergoing endoscopic evaluation were recruited into the study (Table 1,2). Colonic and small intestinal (duodenal and ileal) biopsies were analyzed by multiparameter flow cytometry for mucosal immune cell populations including myeloid cells (classical and non-classical monocytes, dendritic cell subsets), T cells (subsets and activation state), B cells (including plasma cells). Persistence of viral antigens was determined by immunofluorescence microscopy (n=30) using a previously published anti-nucleocapsid (NP) antibody.

Thirty subjects with a previous history of COVID-19 (post-COVID), median of 4 months from diagnosis (range 1-10 months), were recruited and compared with 40 normal volunteer (NV) controls. Relative to controls, post-COVID subjects displayed higher frequencies of classical (CD14⁺) monocytes in both, the colon and the small bowel, while significantly higher frequencies of conventional dendritic cells (cDC) 1 (lin^-HLA-DR^hiCD14^-CD11c⁺CD141⁺) and cDC2 (lin-HLA^-DR^hiCD14^--CD11c⁺CD1c⁺) were noted in the colon only. Among T cell subsets, CD8⁺ tissue resident memory T cells (CD8⁺CD69⁺CD103⁺) were significantly increased in colon of post-COVID subjects compared to NV. Among B cell subsets, plasma cells (CD3^-CD27⁺CD38^hi) trended higher (p=0.06), while mucosal B cells (CD3^-CD19⁺) were significantly lower in the terminal ileum of post-COVID subjects compared to NV. Finally, with IF, we detected SARS-CoV-2 NP in 10 out of 30 (33%) of post-COVID subjects (Figure 1).  There were no significant correlations of these cell populations with either time after the infection or IF positivity.

Innate and adaptive immune cell abnormalities persist in the intestinal mucosa of post-COVID subjects for up to 10 months and may reflect viral persistence or immune cell dysregulation in the intestines. These findings have major implications for understanding the pathogenesis of long term sequela of COVID-19, including long-haul COVID. 

The N-ECCO Consensus provides clarity on the different nursing roles in caring for patients with Crohn’s disease and ulcerative colitis within Europe. The intention is to identify the position of IBD nurses and provide a consensus on the ideal standard of nursing care that patients with IBD can expect, irrespective of level of training or title.