Ulcerative colitis Le Berre, Catherine; Honap, Sailish; Peyrin-Biroulet, Laurent
The Lancet (British edition),
08/2023, Letnik:
402, Številka:
10401
Journal Article
Recenzirano
Ulcerative colitis is a lifelong inflammatory disease affecting the rectum and colon to a variable extent. In 2023, the prevalence of ulcerative colitis was estimated to be 5 million cases around the ...world, and the incidence is increasing worldwide. Ulcerative colitis is thought to occur in people with a genetic predisposition following environmental exposures; gut epithelial barrier defects, the microbiota, and a dysregulated immune response are strongly implicated. Patients usually present with bloody diarrhoea, and the diagnosis is based on a combination of clinical, biological, endoscopic, and histological findings. The aim of medical management is, first, to induce a rapid clinical response and normalise biomarkers and, second, to maintain clinical remission and reach endoscopic normalisation to prevent long-term disability. Treatments for inducing remission include 5-aminosalicylic acid drugs and corticosteroids. Maintenance treatments include 5-aminosalicylic acid drugs, thiopurines, biologics (eg, anti-cytokines and anti-integrins), and small molecules (Janus kinase inhibitors and sphingosine-1-phosphate receptor modulators). Although the therapeutic options are expanding, 10-20% of patients still require proctocolectomy for medically refractory disease. The keys to breaking through this therapeutic ceiling might be the combination of therapeutics with precision and personalised medicine.
Key points
Unlike astrocytes in the brain, the potential role of enteric glial cells (EGCs) in the formation of the enteric neuronal circuit is currently unknown.
To examine the role of EGCs in the ...formation of the neuronal network, we developed a novel neuron‐enriched culture model from embryonic rat intestine grown in indirect coculture with EGCs.
We found that EGCs shape axonal complexity and synapse density in enteric neurons, through purinergic‐ and glial cell line‐derived neurotrophic factor‐dependent pathways.
Using a novel and valuable culture model to study enteric neuron–glia interactions, our study identified EGCs as a key cellular actor regulating neuronal network maturation.
In the nervous system, the formation of neuronal circuitry results from a complex and coordinated action of intrinsic and extrinsic factors. In the CNS, extrinsic mediators derived from astrocytes have been shown to play a key role in neuronal maturation, including dendritic shaping, axon guidance and synaptogenesis. In the enteric nervous system (ENS), the potential role of enteric glial cells (EGCs) in the maturation of developing enteric neuronal circuit is currently unknown. A major obstacle in addressing this question is the difficulty in obtaining a valuable experimental model in which enteric neurons could be isolated and maintained without EGCs. We adapted a cell culture method previously developed for CNS neurons to establish a neuron‐enriched primary culture from embryonic rat intestine which was cultured in indirect coculture with EGCs. We demonstrated that enteric neurons grown in such conditions showed several structural, phenotypic and functional hallmarks of proper development and maturation. However, when neurons were grown without EGCs, the complexity of the axonal arbour and the density of synapses were markedly reduced, suggesting that glial‐derived factors contribute strongly to the formation of the neuronal circuitry. We found that these effects played by EGCs were mediated in part through purinergic P2Y1 receptor‐ and glial cell line‐derived neurotrophic factor‐dependent pathways. Using a novel and valuable culture model to study enteric neuron–glia interactions, our study identified EGCs as a key cellular actor required for neuronal network maturation.
Key points
Unlike astrocytes in the brain, the potential role of enteric glial cells (EGCs) in the formation of the enteric neuronal circuit is currently unknown.
To examine the role of EGCs in the formation of the neuronal network, we developed a novel neuron‐enriched culture model from embryonic rat intestine grown in indirect coculture with EGCs.
We found that EGCs shape axonal complexity and synapse density in enteric neurons, through purinergic‐ and glial cell line‐derived neurotrophic factor‐dependent pathways.
Using a novel and valuable culture model to study enteric neuron–glia interactions, our study identified EGCs as a key cellular actor regulating neuronal network maturation.
Crohn's disease (CD) can affect the entire gastrointestinal tract. Proximal small bowel (SB) lesions are associated with a significant risk of stricturing disease and multiple abdominal surgeries. ...The assessment of SB in patients with CD is therefore necessary because it may have a significant impact on prognosis with potential therapeutic implications. Because of the weak correlation that exists between symptoms and endoscopic disease activity, the "treat-to-target" paradigm has been developed, and the associated treatment goal is to achieve and maintain deep remission, encompassing both clinical and endoscopic remission. Small bowel capsule endoscopy (SBCE) allows to visualize the mucosal surface of the entire SB. At that time, there is no recommendation regarding the use of SBCE during follow-up.
To investigate the impact of SBCE in a treat-to-target strategy in patients with CD.
An electronic literature search was conducted in PubMed and Cochrane library using the following search terms: "capsule endoscopy", in combination with "Crohn's disease" and "treat-to-target" or synonyms. Two authors independently reviewed titles and abstracts identified by the search strategy after duplicates were removed. Following the initial screening of abstracts, all articles containing information about SBCE in the context of treat-to-target strategy in patients with CD were included. Full-text articles were retrieved, reference lists were screened manually to identify additional studies.
Forty-seven articles were included in this review. Two indexes are currently used to quantify disease activity using SBCE, and there is good correlation between them. SBCE was shown to be useful for disease reclassification in patients who are suspected of having or who are diagnosed with CD, with a significant incremental diagnostic yield compared to other diagnostic modalities. Nine studies also demonstrated that the mucosal healing can be evaluated by SBCE to monitor the effect of medical treatment in patients with CD. This review also demonstrated that SBCE can detect post-operative recurrence to a similar extent as ileocolonoscopy, and proximal SB lesions that are beyond the reach of the colonoscope in over half of the patients.
SBCE could be incorporated in the treat-to-target algorithm for patients with CD. Randomized controlled trials are required to confirm its usefulness and reliability in this indication.
Since 2010, substantial progress has been made in artificial intelligence (AI) and its application to medicine. AI is explored in gastroenterology for endoscopic analysis of lesions, in detection of ...cancer, and to facilitate the analysis of inflammatory lesions or gastrointestinal bleeding during wireless capsule endoscopy. AI is also tested to assess liver fibrosis and to differentiate patients with pancreatic cancer from those with pancreatitis. AI might also be used to establish prognoses of patients or predict their response to treatments, based on multiple factors. We review the ways in which AI may help physicians make a diagnosis or establish a prognosis and discuss its limitations, knowing that further randomized controlled studies will be required before the approval of AI techniques by the health authorities.
The protein alpha‐synuclein whose expression is strongly implicated in Parkinson's disease (PD) is not only expressed in the CNS but also in the enteric nervous system (ENS). The growing body of ...evidence suggesting that gastrointestinal inflammation is involved in the development of PD led us to investigate the effects of inflammation on alpha‐synuclein expression in primary culture of rat ENS and in mice with dextran sulfate sodium‐induced colitis. Using western blot and qPCR, we found that both lipopolysaccharide and a combination of tumor necrosis factor‐α and interleukin 1‐β decreased the expression levels of alpha‐synuclein in primary culture of rat ENS, an effect that was prevented in the presence of the p38 inhibitors SB203580 and BIRB 796. Lipopolysaccharide and tumor necrosis factor‐α/interleukin 1‐β had no effect on alpha‐synuclein expression in primary culture of rat CNS and in human erythroid leukemia cells. In mice, acute but not chronic dextran sulfate sodium‐induced colitis was associated with a decreased expression of colonic alpha‐synuclein. As a whole, our findings indicate that acute inflammatory insults down‐regulate alpha‐synuclein expression in the ENS via a p38 pathway. They provide new insights into the widely discussed concepts of alpha‐synuclein expression and aggregation in the ENS in PD and raise issues about the possible role of gastrointestinal inflammation in the development of PD.
Open science badges
This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.
We show that acute inflammatory insults down‐regulate alpha‐synuclein expression in primary culture of enteric nervous system and in the colon of mice. Our findings provide new insights into the widely discussed concepts of alpha‐synuclein expression and aggregation in the enteric nervous system in Parkinson's disease and raise issues about the possible role of gastrointestinal inflammation in the development of Parkinson's disease.
Open Science: This manuscript was awarded with the Open Materials Badge.
For more information see: https://cos.io/our-services/open-science-badges/
Smoking has detrimental effects on Crohn's disease (CD) activity while data on ulcerative colitis (UC) are conflicting. Little is known about the use and impact of alternative smoking products in ...inflammatory bowel diseases (IBD).
To understand the patients' perceptions of the impact of smoking on their IBD and to assess differences between CD and UC patients.
The questionnaire was developed by Philip Morris Products SA in cooperation with European Federation of Crohn's and Ulcerative Colitis Associations. The final survey questionnaire consisted of 41 questions divided in 8 categories: (1) Subject screener; (2) Smoking history; (3) Background information; (4) IBD disease background; (5) Current disease status; (6) Current therapeutics and medications; and (7) Current nicotine/cigarettes use and awareness of the impacts of smoking on IBD. The questionnaire was submitted online from 4
November 2019 to 11th March 2020 through the European Federation of Crohn's and Ulcerative Colitis Associations website to IBD patients who were current smokers or had a history of smoking.
In total 1050 IBD patients speaking nine languages participated to the survey. Among them, 807 (76.9%) patients declared to have ever smoked or consumed an alternative smoking product, with a higher proportion of current cigarette smokers among CD patients (CD: 63.1%
UC: 54.1%,
= 0.012). About two-thirds of the participants declared to have ever stopped cigarette smoking and restarted (67.0%), with a significantly higher proportion among UC patients compared to CD patients (73.1%
62.0%,
= 0.001). We also found significant differences between CD and UC patients in the awareness of the health consequences of smoking in their disease and in the perceived impact of smoking on disease activity, for both cigarettes and alternative smoking products.
This survey found significant differences between CD and UC patients in both awareness and perception of the impact of smoking on their disease. Further efforts should be done to encourage smoking cessation for all IBD patients, including UC patients.
Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are lifelong diseases characterized by chronic inflammation of the gastrointestinal tract leading to its ...progressive and irreversible destruction. Whether early initiation of IBD-specific therapy impacts the long-term course of the disease remains unclear and has to be further explored in prospective disease-modification trials. Historically, surgery and hospitalization rates have been the surrogate markers to measure disease progression in IBD, providing an overview of the effectiveness of medical therapies. However, neither surgery nor hospitalization necessarily reflects a fail in therapeutic medical management, and many confounding factors make them biased outcomes. The Selecting Endpoints for Disease-Modification Trials consensus has defined the disease-modification endpoints required for these trials, including the impact of the disease on patient’s life (health-related quality of life, disability, and fecal incontinence), the mid-term disease complications (bowel damage in CD, IBD-related surgery and hospitalizations, disease extension in UC, extra-intestinal manifestations, permanent stoma, short bowel syndrome), and the development of dysplasia/cancer and mortality in the long term. Most available data in the literature regarding the impact of current therapies on disease progression focused on anti-tumor necrosis factor agents and are based on retrospective or post-hoc studies. Thus, prospective disease-modification trials are pressingly required to explore the effectiveness of early intensified treatment in patients with severe disease or at risk for disease progression.
Background
Analysis of serum biomarkers for the assessment of atrophic gastritis (AG), considered as gastric precancerous lesion, is of growing interest and recommended by current guidelines. Our aim ...was to evaluate the diagnostic performance of a panel of biomarkers (GastroPanel®) for the detection of AG in France, a country of a low gastric cancer (GC) incidence.
Material and Methods
In this prospective, multicenter, cross‐sectional study, consecutive patients considered at increased risk of GC and undergoing upper endoscopy with gastric biopsies were included. Blood samples were collected for the analysis of GastroPanel® (association of Pepsinogens I and II, Gastrin‐17, and Helicobacter pylori serology) using ELISA. The results of GastroPanel® were compared to the results of histology considered as the reference.
Results
Between 2016 and 2019, 344 patients (148 cases with AG, 196 controls without AG) were included. Sensitivity, specificity, positive, and negative predictive values for the detection of AG by GastroPanel® were of 39.9% (95% CI 31.9; 48.2), 93.4% (95% CI 88.9; 96.4), 81.9 (95% CI 71.1; 90.0), and 67.3 (95% CI 61.4; 72.8), respectively. The sensitivity was significantly higher for the detection of severe AG 60.8% (95% CI 46.1; 74.6) P = .015 and corpus AG 61.0% (95% CI 49.2; 72.0), P = .004. Diagnostic performances of GastroPanel® tended to be better than those of Pepsinogen I alone, but the difference did not reach statistical significance (P = .068).
Conclusion
Serum pepsinogen and GastroPanel® tests show promising results for the detection of AG, especially of corpus AG and severe AG, in patients at high risk of GC in France.
: For 30 years, 5-aminosalicylic acid (5-ASA) has been the backbone of therapeutic management in patients with ulcerative colitis (UC). In the biologic era, it still remains the treatment of choice ...in mild-to-moderate UC. Positioning of this therapeutic class in moderate-to-severe UC is less clear.
: Several studies demonstrated the ability of 5-ASA to induce endoscopic remission to a similar extent as anti-TNF therapy on the moderate segment of UC. Histologic remission is achieved after induction in up to 45% of patients treated with topical 5-ASA and 30% with oral formulations. Aminosalicylates offer a favorable safety profile compared to that of immunomodulators and biologics. High-dose 5-ASA therapy may be a valuable option for patients with moderately active disease, and physicians should weigh the pros and cons of this strategy in selected patients. Whether aminosalicylates should be continued in combination with thiopurines or biologic therapy remains under debate.
: In the era of biologics, aminosalicylates remain the first-line therapy in patients with mild UC, and have to be considered in case of moderate UC, given their favorable risk-benefit profile. We suggest that 5-ASA should be used in moderate patients without poor prognostic factors, while biologics should be preferred otherwise.
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