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超越无麸质饮食:乳糜泻治疗的创新。

Beyond the gluten-free diet: Innovations in celiac disease therapeutics.

机构信息

Division of Gastroenterology, Fondazione IRCCS San Gerardo dei Tintori, University of Milano-Bicocca, Monza 20900, Italy.

Department of Gastroenterology, IRCCS San Gerardo dei Tintori, Monza 20900, Lombardy, Italy.

出版信息

World J Gastroenterol. 2024 Oct 14;30(38):4194-4210. doi: 10.3748/wjg.v30.i38.4194.


DOI:10.3748/wjg.v30.i38.4194
PMID:39493330
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11525874/
Abstract

Celiac disease (CD) is an autoimmune disorder exacerbated by the ingestion of gluten in genetically susceptible individuals, leading to intestinal inflammation and damage. This chronic disease affects approximately 1% of the world's population and is a growing health challenge due to its increasing prevalence. The development of CD is a complex interaction between genetic predispositions and environmental factors, especially gluten, culminating in a dysregulated immune response. The only effective treatment at present is a strict, lifelong gluten-free diet. However, adherence to this diet is challenging and often incomplete, so research into alternative therapies has intensified. Recent advances in understanding the molecular and immunological aspects of CD have spearheaded the development of novel pharmacologic strategies that should provide more effective and manageable treatment options. This review examines the latest innovations in CD therapies. The focus is on drugs in advanced clinical phases and targeting specific signaling pathways critical to the disease pathogenesis. We discuss both quantitative strategies such as enzymatic degradation of gluten, and qualitative approaches including immunomodulation and induction of gluten tolerance. Innovative treatments currently under investigation include transglutaminase inhibitors, which prevent the modification of gluten peptides, and nanoparticle-based therapies to recalibrate the immune response. These new therapies not only promise to improve patient outcomes but are also expected to improve quality of life by reducing the burden of dietary restrictions. The integration of these new therapies could revolutionize the treatment of CD and shift the paradigm from strict dietary restrictions to a more flexible and patient-friendly therapeutic approach. This review provides a comprehensive overview of the future prospects of CD treatment and emphasizes the importance of continued research and multidisciplinary collaboration to integrate these advances into standard clinical practice.

摘要

乳糜泻(CD)是一种自身免疫性疾病,在遗传易感性个体中摄入麸质会加剧这种疾病,导致肠道炎症和损伤。这种慢性疾病影响着全球约 1%的人口,由于其发病率不断上升,已成为一个日益严峻的健康挑战。CD 的发生是遗传易感性和环境因素(尤其是麸质)之间复杂相互作用的结果,最终导致免疫反应失调。目前唯一有效的治疗方法是严格的终生无麸质饮食。然而,这种饮食的依从性具有挑战性且常常不完整,因此对替代疗法的研究一直在加强。对 CD 分子和免疫学方面的最新理解进展推动了新型药物治疗策略的发展,这些策略应该为更有效和更易于管理的治疗选择提供依据。本综述探讨了 CD 治疗的最新创新。重点是处于临床后期阶段的药物以及针对疾病发病机制关键信号通路的靶向治疗药物。我们讨论了包括酶法降解麸质在内的定量策略,以及包括免疫调节和诱导麸质耐受在内的定性方法。目前正在研究的创新疗法包括可防止麸质肽修饰的转谷氨酰胺酶抑制剂,以及可重新校准免疫反应的基于纳米颗粒的疗法。这些新疗法不仅有望改善患者的预后,还可以通过减轻饮食限制的负担来提高生活质量。这些新疗法的整合有望彻底改变 CD 的治疗方式,将治疗范式从严格的饮食限制转变为更灵活和患者友好的治疗方法。本综述全面概述了 CD 治疗的未来前景,并强调了持续研究和多学科合作的重要性,以将这些进展整合到标准临床实践中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44d2/11525874/2718d51098b4/WJG-30-4194-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44d2/11525874/7d3b7193a3f8/WJG-30-4194-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44d2/11525874/2718d51098b4/WJG-30-4194-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44d2/11525874/7d3b7193a3f8/WJG-30-4194-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44d2/11525874/2718d51098b4/WJG-30-4194-g002.jpg

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引用本文的文献

[1]
Intestinal celiac disease - related autoantibodies.

Front Immunol. 2025-6-6

[2]
Microbial-derived peptidases are altered in celiac disease, non-celiac gluten sensitivity, and functional dyspepsia: a systematic review and re-analysis of the duodenal microbiome.

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[3]
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Immun Inflamm Dis. 2025-5

[4]
The CXCR3/PLC/IP3-IP3R axis is responsible for the ignition of UPR in intestinal epithelial cells exposed to gliadin peptide, during the onset of celiac disease.

Biol Direct. 2025-3-31

本文引用的文献

[1]
Effect of prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet.

World J Gastroenterol. 2024-3-21

[2]
Gluten-Free Diet Compliance in Children With Celiac Disease and Its Effect on Clinical Symptoms: A Retrospective Cohort Study.

Cureus. 2023-12-9

[3]
Zonulin as a Biomarker for the Development of Celiac Disease.

Pediatrics. 2024-1-1

[4]
The Oral Transglutaminase 2 Inhibitor ZED1227 Accumulates in the Villous Enterocytes in Celiac Disease Patients during Gluten Challenge and Drug Treatment.

Int J Mol Sci. 2023-6-28

[5]
Safety and tolerability of KAN-101, a liver-targeted immune tolerance therapy, in patients with coeliac disease (ACeD): a phase 1 trial.

Lancet Gastroenterol Hepatol. 2023-8

[6]
Maladaptive Food Attitudes and Behaviors in Individuals with Celiac Disease and Their Association with Quality of Life.

Dig Dis Sci. 2023-7

[7]
Latiglutenase Protects the Mucosa and Attenuates Symptom Severity in Patients With Celiac Disease Exposed to a Gluten Challenge.

Gastroenterology. 2022-12

[8]
A Randomized Trial of a Transglutaminase 2 Inhibitor for Celiac Disease.

N Engl J Med. 2021-7-1

[9]
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Mediators Inflamm. 2021

[10]
Gluten Degradation, Pharmacokinetics, Safety, and Tolerability of TAK-062, an Engineered Enzyme to Treat Celiac Disease.

Gastroenterology. 2021-7

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