Abstract
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.
Highlights
Introduction to Inflammatory BowelDiseases (IBD)Inflammatory bowel diseases (IBD) are disabling, noncommunicable, progressive and incurable immune-mediated inflammatory diseases (IMIDs)
Immune dysfunction mechanisms, systemic inflammation, dysregulation of gut microbiota, and wide therapeutic overlaps support the hypothesis of a common pathogenesis between Crohn’s disease (CD) and ulcerative colitis (UC); the differences occur in terms of the site and nature of the inflamed lesions [7,8,10]
Multi-shell NPs of a calcium phosphate (CaP) core were coated with siRNA directed at mediators of inflammation, such as TNF-α, encapsulated in PLGA coated with an outer layer of polyethyleneimine
Summary
The resident gut microbiota are involved in several vital host physiological processes, including the development of the gut immune system, digestion of dietary factors, and colonization resistance against incoming pathogens, but it can be associated with UC and CD pathogenesis [24,25]. Some studies reported that around 40% of ileal colitis disease patients have an overgrowth of adherent/invasive E. coli (AIEC) compared to healthy individuals [26,50,51] These promote IBD, as their genome can adapt to a specific and susceptible host [52]. Shoaei et al studied the presence of C. difficile in faecal samples in UC patients, revealing that all patients with C. difficile infection exhibited moderate-to-severe IBD, correlated with exposure to different antimicrobial and anti-inflammatory agents [58] Fungi, on another hand, represent
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