Inflammatory bowel disease (IBD), which is typically classified as either ulcerative colitis or Crohn’s disease, is a chronic

The gap

Evidence profile

Sourced from the future work of the source papers, classified as general, drawn from work published between 2024 and 2026, spanning 5 journals. Those papers have been cited 76 times in total.

Supporting evidence — 5 representative gaps

• Clinical combination therapy for IBD and promising co-delivery strategies (2026) · Inflammopharmacology · doi

  IBD is a chronic, relapsing inflammatory disorder driven by multifactorial pathogenesis, frequently refractory to conventional therapy, and clinically defined by symptoms including abdominal pain, chronic diarrhea, and nutritional deficits (Podolsky 2002). Combination therapies, such as the pairing of IFX and AZA, have been shown to improve clinical remission rates in patients with UC, increasing the 16-week remission rate to 39.7%, significantly outper- forming monotherapy (Panaccione et al. 2014). However, combination therapies face challenges such as optimizing dosages, systemic toxicity (e.g., the combination of anti- TNF drugs and immunosuppressants increases the risk of severe infections (Singh et al. 2020)), and poor bioavail- ability. Nanodelivery systems, such as Tof@BSA-Chs-CP NPs (Wu et al. 2025), enable targeted drug delivery, regulate the expression of pro-inflammatory and anti-inflammatory cytokines, enhance local drug concentrations, and reduce systemic toxicity. Nonetheless, their clinical translation is in the early stages, and further validation is needed to con- firm their safety and scalability. Innovative strategies that combine traditional drugs, such as 5-ASA, with novel com- pounds (e.g., PL reduces cell apoptosis, inhibits the NF-κB pathway, and suppresses inflammatory cytokine expression (Carter et al. 2003; Fennis et al. 2002); PNU282987 com- bined with SHP099 enhances anti-inflammatory effects and 1 3Clinical combination therapy for IBD and promising co-delivery strategiesmitigates the side effects of high-dose PNU282987 (Xiao et al. 2020)) have demonstrated potential for improving both efficacy and safety. Future IBD treatments should integrate clinical experience with AI-assisted drug design, focusing on repositioning existing drugs and discovering safer, more effective drug combinations and optimal dosages (Visan and Negut 2024). Additionally, intelligent nanocarriers should be developed to overcome current delivery barriers, ulti- mately enabling the clinical translation of combined drug delivery systems. Acknowledgements Figure 1 was created using BioRender. Author contributions Bing Wang and Jianfeng Li contributed to the conception of the review, Huili Dai contributed significantly to the revision. Xinlong Wang and Weihua Xu contributed significantly to the complete manuscript preparation, and Yushan Wu and Peifeng Liu contributed to the constructive discussions. All authors have read and approved the final manuscript. Funding This work was supported by the Program of the Shang- hai Committee of Science and Technology, China (grant number 24010701800), the Talent Support Project of Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital (grant num- ber ZPRC-2023A-11, ZPRC-2023A-18) and Zhang Xia Expert Work- station of the Yunnan Province (grant number 202205AF150068). Data availability No datasets were generated or analysed during the current study.

  generalfuture work
  Keywords: inflammatory clinical drug combination delivery contributed anti drugs grant chronic therapy therapies remission dosages systemic
• Dietary polysaccharides in the management of inflammatory bowel disease: recent advances (2026) · Frontiers in Nutrition · doi

  5.1 Summary of key findings With the worldwide prevalence of IBD continuing to rise and the currently available pharmacological treatments being limited by side effects and incomplete efficacy, there is an urgent need to develop new therapeutic strategies. Accumulating evidence indicates that dietary polysaccharides play a critical role in the prevention and management of IBD (9, 78, 117, 122, 133). FIGURE 2 Mechanistic Studies on the Treatment of IBD with Dietary-Derived Polysaccharides. In IBD, intestinal inflammation is characterized by barrier disruption, increased permeability, and immune cell infiltration. Dietary polysaccharides derived from plant (e.g., pectins, β-glucans, fucoidans), fungal (e.g., lentinan), animal (e.g., chondroitin, hyaluronic acid), and microbial sources (e.g., xanthan gum) reach the colon and serve as fermentable substrates for the gut microbiota. Through microbial fermentation and metabolic transformation, these polysaccharides promote microbiota remodeling, characterized by enrichment of beneficial bacteria (e.g., Bifidobacterium, Lactobacillus) and suppression of pathobionts (e.g., Escherichia), accompanied by increased production of bioactive metabolites such as short-chain fatty acids (SCFAs), optimized bile acids, and tryptophan-derived metabolites. These changes contribute to restoration of the intestinal barrier by enhancing MUC2 mucus layer thickness, upregulating tight junction proteins (ZO-1, occludin, claudin-1), and reducing epithelial permeability. Simultaneously, polysaccharides modulate immune homeostasis by suppressing pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), promoting anti-inflammatory responses (IL-10, TGF-β), facilitating macrophage polarization from M1 to M2, and inhibiting NF-κB/MAPK/NLRP3 signaling pathways. Together, these effects illustrate a coordinated microbiota–barrier–immune regulatory axis underlying the therapeutic potential of dietary polysaccharides in IBD.

  generalfuture work
  Keywords: polysaccharides dietary derived barrier immune microbiota therapeutic intestinal characterized increased permeability microbial metabolites acids ammatory
• Anti-IL23/12 agents and JAK inhibitors for inflammatory bowel disease (2024) · Frontiers in Immunology · cited 27× · doi

  Inflammatory bowel disease (IBD), which is typically classified as either ulcerative colitis or Crohn’s disease, is a chronic, immune- mediated, inflammatory disease of the digestive tract. The field of IBD therapeutics has undergone tremendous improvements with the development of new drugs that target various pathways, such as the IL-12/IL-23 pathway and the JAK/STAT pathway. Most of these new drugs are in advanced phases of study and have shown promising efficacy in patients with IBD. Although JAK-targeting small molecules are in early phase trials, they represent novel therapeutic options for IBD treatment. The emergence of these novel drugs means that we have a large number of available options, and they might enable new strict endpoints in IBD therapy to be achieved. In addition, further studies comparing the clinical response rate of these approved agents with that of traditional agents are necessary to obtain accurate results, and long-term safety data are needed. With the introduction of additional approved drugs in the future, it will be crucial to identify biomarkers to predict and monitor clinical success to enable personalized therapy in IBD patients.

  generalfuture work
  Keywords: drugs disease ammatory pathway patients novel options enable therapy clinical approved agents bowel typically classi
• Current Treatments, Emerging Therapeutics, and Natural Remedies for Inflammatory Bowel Disease (2024) · Molecules · cited 40× · doi

  Conventional  treatments  using  corticosteroids,  aminosalicylates,  and  immunosup‐ pressants have been fundamental options for IBD patients despite associated side effects.  The advent of biologics, including anti‐TNFs, JAK inhibitors, and, recently, anti‐integrins,  has significantly improved IBD treatment outcomes. However, variable efficacy, side ef‐ fects, and high costs have been major constraints in daily clinical practice. Many new IBD  therapeutics are in the pipeline, but they require more clinical validations and safety as‐ sessments using more extensive IBD cohort studies.    Natural products from plants, helminths, and microbes exhibit considerable promise  as anti‐inflammatory agents for treating IBD, including a few already in early clinical trial  phases. (e.g., curcumin and berberine). Helminth excretory/secretory products and probi‐ otic microbial strains, including Lactobacillus species, have also shown efficacy in preclin‐ ical and clinical studies. However, they have to pass through more validations for their  safety and efficacy before their appearance in the clinical application. The role of the gut  microbiome in IBD is rapidly advancing, with probiotics and prebiotics exhibiting poten‐ tial. However, the exact mechanisms of action remain unclear. Hence, further intensive  research is crucial to ascertain specific microbial strains with therapeutic potential, clarify  their mechanisms of action, and address the current limited knowledge regarding long‐ term safety and efficacy.  Artificial  intelligence  (AI)‐assisted  technologies,  including  machine  learning  and  deep learning, have streamlined chemical structure forecasting, synthesis pathway pro‐ posals, and drug–target interaction elucidation processes. AI‐assisted tools, such as mo‐ lecular docking and protein–protein interaction studies, have identified promising anti‐ inflammatory leads such as curcumin and epigallocatechin gallate. However, AI‐assisted  approaches often need more transparency in their predictions and elucidation of under‐     Molecules 2024, 29, 3954  19  of  24  lying pharmacological mechanisms. Therefore, it is crucial to develop interpretable ma‐ chine learning models to enhance clinical applicability and ensure the safety and reliabil‐ ity of AI‐driven predictions. Thorough experimental and clinical validation of these mod‐ els is essential before their implementation in clinical practice. While current treatment  options have significantly improved IBD patient care, applying AI platforms and inter‐ disciplinary collaborations may further speed up the search for better treatments for IBD.  In  doing so,  we  may  be able  to  see  at  least  a  few  new  IBD drugs  in  the  next  couple  of  decades.  Author Contributions: Conceptualization, P.W., T.J. and K.Y.; writing—original draft preparation,  K.Y. and T.J.; writing—review and editing, P.W., funding acquisition, P.W. All authors have read  and agreed to the published version of the manuscript.  Funding: This research was funded by a James Cook University Postgraduate Research Scholarship  (JCUPRS) to T.J. and an NHMRC Ideas Grant (APP1183323 and APP 2029349) to P.W.  Institutional Review Board Statement: Not applicable.  Informed Consent Statement: Not applicable.  Data Availability Statement: Data sharing is not applicable.  Conflicts of Interest: The authors declare no conflicts of interest.

  generalfuture work
  Keywords: clinical including anti efficacy safety mechanisms assisted learning statement applicable treatments using options side improved
• Inflammatory Bowel Disease: Understanding Therapeutic Effects of Distinct Molecular Inhibitors as the Key to Current and Future Advanced Therapeutic Strategies (2025) · Biomedicines · cited 9× · doi

  7.1. Advanced Combination Therapy Despite the introduction of new therapies targeting different inflammatory pathways, a proportion of IBD patients still fail to achieve remission or experience secondary loss of response. Breaking the therapeutic ceiling remains a major challenge. Among the emerging approaches, advanced combination therapy (ACT), including biologic-biologic and biologic- small molecule pairings, represents a promising strategy. The immune dysregulation observed in IBD is a complex process involving a multifaceted interplay of cytokines, immune cells, and gut barrier dysfunction. Given that multiple inflammatory pathways are concurrently active in a single patient, a monotherapeutic approach targeting only one pathway may be insufficient to achieve adequate control of the inflammation [91]. The rationale for using advanced combination therapy is based on several key princi- ples. The primary aim is to exploit pharmacodynamic complementarity by simultaneously targeting non-overlapping immune pathways to achieve greater disease control than ei- ther agent alone, thus avoiding potential mechanistic escape and loss of response [92]. Furthermore, combination therapy can offer a key “temporal advantage”. This involves using a fast-onset agent (e.g., JAKi) to induce control while a slower-onset maintenance agent (e.g., Vedolizumab, Ustekinumab) takes effect, allowing for a subsequent sequential de-escalation of the initial agent. Another advantage is the ability to address different dis- ease manifestations. This is achieved by associating a gut-selective drug to target luminal inflammation with a systemic agent that can also address extraintestinal manifestations (EIMs) or concomitant immune-mediated inflammatory diseases (IMIDs). The synergistic potential of combination therapy provides a strong rationale for its use. A compelling example is the association between anti-TNF and anti-IL-23 therapies. In patients refractory to anti-TNF treatment, there is a notable upregulation of mucosal IL-23p19, IL-23R and IL-17A. This is accompanied by an expansion of apoptosis-resistant TNFR2+IL23R+ T cells, which are activated by IL-23 originating from CD14+ macrophages, a cell population more prevalent in non-responders. As functional studies have demon- strated, IL-23 is able to counteract the pro-apoptotic effects of anti-TNF agents on mucosal T cells. This mechanistic insight suggests that targeting the IL-23 pathway can overcome resistance to anti-TNF therapy, leading to a synergistic therapeutic outcome [55]. Another example of combined therapeutic effect is the association of an agent that targets leukocyte trafficking with a cytokine pathway blocker. Specifically, while the α4β7 integrin inhibitor vedolizumab effectively reduces gut homing of immune cells, it does not inhibit the inflammatory activity of T-cells that have already infiltrated the mucosa. When combined with a cytokine inhibitor (such as ustekinumab or an anti-TNF agent),

  generalfuture work
  Keywords: agent therapy anti combination immune cells targeting inflammatory advanced pathways achieve therapeutic biologic pathway control

Questions about this gap