Are Patients with Inflammatory Bowel Disease at Increased Risk for Covid-19 Infection?

Abstract Crohn’s disease [CD] and ulcerative colitis [UC], the main inflammatory bowel diseases [IBD] in humans, are chronic, immune-inflammatory diseases, the pathogenesis of which suggests a complex interaction between environmental factors and genetic susceptibility. These disabling conditions affect millions of individuals and, together with the drugs used to treat them, can put patients at risk of developing complications and other conditions. This is particularly relevant today, as coronavirus disease [Covid-19] has rapidly spread from China to countries where IBD are more prevalent, and there is convincing evidence that Covid-19-mediated morbidity and mortality are higher in subjects with comorbidities. The primary objectives of this Viewpoint are to provide a focused overview of the factors and mechanisms by which the novel severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infects cells and to illustrate the link between such determinants and intestinal inflammation. We also provide clues about the reasons why the overall IBD population might have no increased risk of developing SARS-CoV-2 infection and highlight the potential of cytokine blockers, used to treat IBD patients, to prevent Covid-driven pneumonia.

Download Full-text

The application of omics techniques to understand the role of the gut microbiota in inflammatory bowel disease

Therapeutic Advances in Gastroenterology ◽

10.1177/1756284818822250 ◽

2019 ◽

Vol 12 ◽

pp. 175628481882225 ◽

Cited By ~ 14

Author(s):

Jonathan P. Segal ◽

Benjamin H. Mullish ◽

Mohammed Nabil Quraishi ◽

Animesh Acharjee ◽

Horace R. T. Williams ◽

...

Keyword(s):

Systems Biology ◽

Gut Microbiota ◽

Potential Role ◽

Intestinal Inflammation ◽

Clinical Care ◽

Complex Interaction ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Compositional Changes

The aetiopathogenesis of inflammatory bowel diseases (IBD) involves the complex interaction between a patient’s genetic predisposition, environment, gut microbiota and immune system. Currently, however, it is not known if the distinctive perturbations of the gut microbiota that appear to accompany both Crohn’s disease and ulcerative colitis are the cause of, or the result of, the intestinal inflammation that characterizes IBD. With the utilization of novel systems biology technologies, we can now begin to understand not only details about compositional changes in the gut microbiota in IBD, but increasingly also the alterations in microbiota function that accompany these. Technologies such as metagenomics, metataxomics, metatranscriptomics, metaproteomics and metabonomics are therefore allowing us a deeper understanding of the role of the microbiota in IBD. Furthermore, the integration of these systems biology technologies through advancing computational and statistical techniques are beginning to understand the microbiome interactions that both contribute to health and diseased states in IBD. This review aims to explore how such systems biology technologies are advancing our understanding of the gut microbiota, and their potential role in delineating the aetiology, development and clinical care of IBD.

Download Full-text

Improving the Efficacy of Mesenchymal/Stromal-Based Therapy for Treatment of Inflammatory Bowel Diseases

Biomedicines ◽

10.3390/biomedicines9111507 ◽

2021 ◽

Vol 9 (11) ◽

pp. 1507

Author(s):

Mercedes Lopez-Santalla ◽

Marina Inmaculada Garin

Keyword(s):

Clinical Trials ◽

Immune Responses ◽

Inflammatory Bowel Diseases ◽

Intestinal Inflammation ◽

The Novel ◽

Beneficial Effects ◽

Commensal Microbiota ◽

Bowel Diseases ◽

Inflammatory Processes ◽

Inflammatory Bowel

Inflammatory bowel diseases (IBD) consisting of persistent and relapsing inflammatory processes of the intestinal mucosa are caused by genetic, environmental, and commensal microbiota factors. Despite recent advances in clinical treatments aiming to decrease inflammation, nearly 30% of patients treated with biologicals experienced drawbacks including loss of response, while others can develop severe side effects. Hence, novel effective treatments are highly needed. Mesenchymal stem/stromal cell (MSCs) therapy is an innovative therapeutic alternative currently under investigation for IBD. MSCs have the inherent capacity of modulating inflammatory immune responses as well as regenerating damaged tissues and are therefore a prime candidate to use as cell therapy in patients with IBD. At present, MSC-based therapy has been shown preclinically to modulate intestinal inflammation, whilst the safety of MSC-based therapy has been demonstrated in clinical trials. However, the successful results in preclinical studies have not been replicated in clinical trials. In this review, we will summarize the protocols used in preclinical and clinical trials and the novel approaches currently under investigation which aim to increase the beneficial effects of MSC-based therapy for IBD.

Download Full-text

Dichotomous roles of neutrophils in modulating pathogenic and repair processes of inflammatory bowel diseases

Precision Clinical Medicine ◽

10.1093/pcmedi/pbab025 ◽

2021 ◽

Author(s):

Huimin Chen ◽

Xiaohan Wu ◽

Chunjin Xu ◽

Jian Lin ◽

Zhanju Liu

Keyword(s):

Immune Cells ◽

Inflammatory Bowel Diseases ◽

Intestinal Inflammation ◽

Critical Role ◽

Mucosal Inflammation ◽

Repair Processes ◽

Microbial Invasion ◽

Increased Risk ◽

Bowel Diseases ◽

Inflammatory Bowel

Abstract Neutrophils are considered as complex innate immune cells and play a critical role in maintaining intestinal mucosal homeostasis. They exert robust pro-inflammatory effects and recruit other immune cells in the acute phase of pathogen infection and intestinal inflammation, but paradoxically, they also limit exogenous microbial invasion and facilitate mucosal restoration. Hyperactivation or dysfunction of neutrophils results in abnormal immune responses, leading to multiple autoimmune and inflammatory diseases including systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel diseases (IBD). As a refractory intestinal inflammatory disease, the pathogenesis and progression of IBD are associated with complicated immune response processes in which neutrophils are profoundly involved. However, the consensus on potential roles of neutrophils in modulating pathogenic and repair processes of IBD remains not fully understood. Accumulated infiltrating neutrophils cross the epithelial barrier and contribute to microbial dysbiosis, aggravated intestinal architectural damage, compromised resolution of intestinal inflammation and increased risk of thrombosis during IBD. Paradoxically, activated neutrophils are also associated with effective elimination of invaded microbiota, promoted angiogenesis and tissue restoration of gut mucosa in IBD. Here, we discuss the beneficial and detrimental roles of neutrophils in the onset and resolution of intestinal mucosal inflammation and provide a precise overview of neutrophil functions in the pathogenesis of IBD.

Download Full-text

Is LRRK2 the missing link between inflammatory bowel disease and Parkinson’s disease?

npj Parkinson s Disease ◽

10.1038/s41531-021-00170-1 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Mary K. Herrick ◽

Malú G. Tansey

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Immune Cells ◽

Intestinal Inflammation ◽

Inflammatory Diseases ◽

Increased Risk ◽

Increase Risk ◽

Inflammatory Processes ◽

Inflammatory Bowel ◽

Peripheral Immune Cells

AbstractLinks that implicate the gastrointestinal system in Parkinson’s disease (PD) pathogenesis and progression have become increasingly common. PD shares several similarities with Crohn’s disease (CD). Intestinal inflammation is common in both PD and CD and is hypothesized to contribute to PD neuropathology. Mutations in leucine-rich repeat kinase 2 (LRRK2) are one of the greatest genetic contributors to PD. Variants in LRRK2 have also been associated with increased incidence of CD. Since its discovery, LRRK2 has been studied intensely in neurons, despite multiple lines of evidence showing that LRRK2 is highly expressed in immune cells. Based on the fact that higher levels of LRRK2 are detectable in inflamed colonic tissue from CD patients and in peripheral immune cells from sporadic PD patients relative to matched controls, we posit that LRRK2 regulates inflammatory processes. Therefore, LRRK2 may sit at a crossroads whereby gut inflammation and higher LRRK2 levels in CD may be a biomarker of increased risk for sporadic PD and/or may represent a tractable therapeutic target in inflammatory diseases that increase risk for PD. Here we will focus on reviewing how PD and CD share overlapping phenotypes, particularly in terms of LRRK2 in the context of the immune system, that could be targeted in future therapies.

Download Full-text

Neurological presentations of inflammatory bowel diseases

Medical alphabet ◽

10.33667/2078-5631-2021-3-34-42 ◽

2021 ◽

pp. 34-42

Author(s):

Yu. O. Shulpekova ◽

V. U. Ablaev ◽

I. V. Damulin

Keyword(s):

Inflammatory Bowel Diseases ◽

Neurological Disorders ◽

Intestinal Inflammation ◽

Cranial Nerves ◽

Cranial Neuropathy ◽

Drug Induced ◽

Axonal Polyneuropathy ◽

Increased Risk ◽

Bowel Diseases ◽

Inflammatory Bowel

The aim. To characterize the main types of neurological manifestations in inflammatory bowel diseases – Crohn’s disease and ulcerative colitis.Main concepts. Neurological disorders represent an important aspect of extraintestinal inflammatory bowel diseases (IBD) manifestations. According to publications, the incidence of psycho-neurological syndromes varies from 0.25% to 47.50% that apparently depends on the patient’s selection in studies. Neurological signs are not always associated with IBD activity and may precede the manifestation of intestinal inflammation. The most typical include cerebral thromboembolism, peripheral and cranial neuropathies, demyelinating disorders, and cerebral vasculitis. The incidence of ischemic stroke in IBD can reach 6.4%, with approx. 20% of affected persons under 17 y.o. Hemiparesis is the predominant consequence. The risk of intracranial venous thrombosis is increased depending on the activity of intestinal inflammation; this complication can precede manifestation of IBD. Fifty per cent increased risk of multiple sclerosis in IBD patients was shown. The types of peripheral nerves involvement include mononeuropathy, plexopathy, multiple mononeuropathy, compression neuropathy, polyneuropathy and cranial neuropathy. Peripheral neuropathy may be found in 32–37% of IBD patients with a special examination. Demyelinating type, sensory axonal polyneuropathy with thin and thick fibers damage, and motor axonal polyneuropathy with thick fibers damage are observed approximately in equal proportions. It is important to differentiate ‘primary’ neuropathy with vitamin B12 and folic acid deficient, alcoholic, diabetic and drug-induced neuropathy. Clinical improvement is usually seen in the course of immunosuppressive therapy. Cranial neuropathy (mostly of II, VI, VII, VIII of cranial nerves) is described in IBD. Neurological disorders associated with administration of metronidazole, sulfasalazine, cyclosporin A, antibodies to TNF-α and integrins α4 and α4ß7 continue to be highly actual.Conclusion. There is a variety of neurologic syndromes in IBD which represents an important part of extraintestinal manifestations. Mild psychoneurological disorders may be not recognized in time. The majority of symptoms and signs may regress in the course of treatment of IBD and nutrients deficiency correction. The special attention should be paid to neurological status control while the biologic and immunosuppressor agents and metronidazole are administered.

Download Full-text

Drug Targeting of Inflammatory Bowel Diseases by Biomolecules

Nanomaterials ◽

10.3390/nano11082035 ◽

2021 ◽

Vol 11 (8) ◽

pp. 2035

Author(s):

Joana Costa Antunes ◽

Catarina Leal Seabra ◽

Joana Margarida Domingues ◽

Marta Oliveira Teixeira ◽

Cláudia Nunes ◽

...

Keyword(s):

Opportunistic Infections ◽

Inflammatory Diseases ◽

Treatment Options ◽

Stimuli Responsive ◽

Triggered Release ◽

Healthy State ◽

Increased Risk ◽

Bowel Diseases ◽

Inflammatory State ◽

Inflammatory Bowel

Inflammatory bowel disease (IBD) is a group of disabling, destructive and incurable immune-mediated inflammatory diseases comprising Crohn’s disease (CD) and ulcerative colitis (UC), disorders that are highly prevalent worldwide and demand a large investment in healthcare. A persistent inflammatory state enables the dysfunction and destruction of healthy tissue, hindering the initiation and endurance of wound healing. Current treatments are ineffective at counteracting disease progression. Further, increased risk of serious side effects, other comorbidities and/or opportunistic infections highlight the need for effective treatment options. Gut microbiota, the key to preserving a healthy state, may, alternatively, increase a patient’s susceptibility to IBD onset and development given a relevant bacterial dysbiosis. Hence, the main goal of this review is to showcase the main conventional and emerging therapies for IBD, including microbiota-inspired untargeted and targeted approaches (such as phage therapy) to infection control. Special recognition is given to existing targeted strategies with biologics (via monoclonal antibodies, small molecules and nucleic acids) and stimuli-responsive (pH-, enzyme- and reactive oxygen species-triggered release), polymer-based nanomedicine that is specifically directed towards the regulation of inflammation overload (with some nanosystems additionally functionalized with carbohydrates or peptides directed towards M1-macrophages). The overall goal is to restore gut balance and decrease IBD’s societal impact.

Download Full-text

Systematic Review with Meta-analysis: The Impact of Co-occurring Immune-mediated Inflammatory Diseases on the Disease Course of Inflammatory Bowel Diseases

Inflammatory Bowel Diseases ◽

10.1093/ibd/izaa167 ◽

2020 ◽

Cited By ~ 1

Author(s):

Mohamed Attauabi ◽

Mirabella Zhao ◽

Flemming Bendtsen ◽

Johan Burisch

Keyword(s):

Systematic Review ◽

Risk Ratio ◽

Inflammatory Diseases ◽

Meta Analysis ◽

Disease Course ◽

Immune Mediated ◽

Increased Risk ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

The Impact

Abstract Background and Aims Patients with inflammatory bowel diseases (IBDs) are at risk of developing a variety of other immune-mediated inflammatory diseases (IMIDs). The influence of co-occurring IMIDs on the disease course of IBD remains unknown. The aim of this study was therefore to conduct a systematic review and meta-analysis of the impact of IMIDs on phenotypic presentation and outcome in patients with IBD. Methods PubMed and Embase were searched from their earliest records through December 2018 and updated in October 2019 for studies reporting proportions or ratios of IBD-related disease outcomes in patients with and without co-occurring IMIDs. Meta-analyses were performed to estimate summary proportions and risks of the main outcomes. PRISMA guidelines were used, and study quality was assessed according to the Newcastle-Ottawa Scale. Results A total of 93 studies were identified, comprising 16,064 IBD patients with co-occurring IMIDs and 3,451,414 IBD patients without IMIDs. Patients with IBD and co-occurring IMIDs were at increased risk of having extensive colitis or pancolitis (risk ratio, 1.38; 95% Cl, 1.25–1.52; P < 0.01, I2 = 86%) and receiving IBD-related surgeries (risk ratio, 1.17; 95% Cl, 1.01–1.36; P = 0.03; I2 = 85%) compared with patients without IMIDs. Co-occurrence of IMIDs other than primary sclerosing cholangitis in patients with IBD was associated with an increased risk of receiving immunomodulators (risk ratio, 1.15; 95% Cl, 1.06–1.24; P < 0.01; I2 = 60%) and biologic therapies (risk ratio, 1.19; 95% Cl, 1.08–1.32; P < 0.01; I2 = 53%). Conclusion This meta-analysis found that the presence of co-occurring IMIDs influences the disease course of IBD, including an increased risk of surgery and its phenotypical expression.

Download Full-text

IKKα controls ATG16L1 degradation to prevent ER stress during inflammation

Journal of Experimental Medicine ◽

10.1084/jem.20161867 ◽

2017 ◽

Vol 214 (2) ◽

pp. 423-437 ◽

Cited By ~ 35

Author(s):

Michaela A. Diamanti ◽

Jalaj Gupta ◽

Moritz Bennecke ◽

Tiago De Oliveira ◽

Mallika Ramakrishnan ◽

...

Keyword(s):

Intestinal Inflammation ◽

Inflammatory Diseases ◽

Intestinal Epithelial ◽

Unfolded Protein ◽

Epithelial Regeneration ◽

Iκb Kinase ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Protein Response ◽

Oligomerization Domain

Inhibition of the IκB kinase complex (IKK) has been implicated in the therapy of several chronic inflammatory diseases including inflammatory bowel diseases. In this study, using mice with an inactivatable IKKα kinase (IkkαAA/AA), we show that loss of IKKα function markedly impairs epithelial regeneration in a model of acute colitis. Mechanistically, this is caused by compromised secretion of cytoprotective IL-18 from IKKα-mutant intestinal epithelial cells because of elevated caspase 12 activation during an enhanced unfolded protein response (UPR). Induction of the UPR is linked to decreased ATG16L1 stabilization in IkkαAA/AA mice. We demonstrate that both TNF-R and nucleotide-binding oligomerization domain stimulation promote ATG16L1 stabilization via IKKα-dependent phosphorylation of ATG16L1 at Ser278. Thus, we propose IKKα as a central mediator sensing both cytokine and microbial stimulation to suppress endoplasmic reticulum stress, thereby assuring antiinflammatory function during acute intestinal inflammation.

Download Full-text

Significance of serum palmitoleic acid levels in inflammatory bowel disease

Scientific Reports ◽

10.1038/s41598-021-95923-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yuko Akazawa ◽

Tomohito Morisaki ◽

Hiroko Fukuda ◽

Kiyuu Norimatsu ◽

Junya Shiota ◽

...

Keyword(s):

Palmitoleic Acid ◽

Inflammatory Diseases ◽

Activity Index ◽

Elevated Serum ◽

High Serum ◽

Unknown Etiology ◽

Increased Risk ◽

Bowel Diseases ◽

Disease Site ◽

Inflammatory Bowel

AbstractInflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn’s disease (CD), are chronic intestinal diseases of unknown etiology that present with variable disease extents and outcomes. The use of biomarkers for the diagnosis and management of IBDs is considered beneficial. Palmitoleic acid (PO) is an adipose tissue-derived mono-unsaturated free fatty acid that potentially serves as a lipokine in metabolic and inflammatory diseases. The aim of this study was to investigate the significance of PO levels in the serum of patients with UC and CD. The study included patients with UC (n = 22), patients with CD (n = 35), and controls (n = 22). The levels of serum PO were analyzed using gas chromatography. The association of serum PO levels with the clinical features and disease outcomes in IBD was examined. Serum PO levels were significantly higher in patients with CD than in controls, whereas no difference in these levels was observed between patients with UC and controls. Serum PO levels were significantly associated with the CD activity index. Additionally, high serum PO levels were associated with an increased risk of surgical intervention requirement during follow-up. In a pilot study with a few patients, high PO levels were observed in the mesenteric tissue in the active disease site of patients with CD (n = 7) compared with those with colon cancer (n = 6). Elevated serum PO levels might serve as a marker for local inflammation and prognosis in patients with CD.

Download Full-text

Thrombosis in IBD in the Era of JAK Inhibition

Current Drug Targets ◽

10.2174/1389450121666200902164240 ◽

2020 ◽

Vol 22 (1) ◽

pp. 126-136

Author(s):

Virginia Solitano ◽

Gionata Fiorino ◽

Ferdinando D’Amico ◽

Laurent Peyrin-Biroulet ◽

Silvio Danese

Keyword(s):

Small Molecules ◽

Arterial Thrombosis ◽

Protective Role ◽

Jak Inhibitors ◽

Thrombotic Risk ◽

Increased Risk ◽

Bowel Diseases ◽

Thrombotic Complications ◽

Inflammatory Bowel ◽

Inflammatory Effect

: Patients with inflammatory bowel diseases (IBD) have an increased risk of thrombosis. The interaction between inflammation and coagulation has been extensively studied. It is well-known that some drugs can influence the haemostatic system, but several concerns on the association between therapies and increased risk of thrombosis remain open. While biologics seem to have a protective role against thrombosis via their anti-inflammatory effect, some concerns about an increased risk of thrombosis with JAK inhibitors have been raised. We conducted a literature review to assess the association between biologics/small molecules and venous/arterial thrombotic complications. An increased risk of venous and arterial thrombosis was found in patients treated with corticosteroids, whereas anti-TNF were considered protective agents. No thromboembolic adverse event was reported with vedolizumab and ustekinumab. In addition, thromboembolic events rarely occurred in patients with ulcerative colitis (UC) after therapy with tofacitinib. The overall risk of both venous and arterial thrombosis was not increased based on the available evidence. Finally, in the era of JAK inhibitors, treatment should be individualized by evaluating the pre-existing potential thrombotic risk balanced with the intrinsic risk of the medication used.

Download Full-text