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Biochemistry, Genetics and Molecular Biology · Research topic

Open research questions in Inflammatory Bowel Disease

91 unresolved questions extracted from the limitations and future-work sections of 717 Inflammatory Bowel Disease papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Whether this worsening reflects the natural history of paradoxical psoriasis under continued IFX exposure or is specifically related to the subcutaneous route of administration remains unclear.

    Subcutaneous infliximab as a maintenance option in pediatric IBD: a real-world cohort including younger and lower-weight children · 2026 · DOI

  • Although biologic therapy has improved disease control, its relationship with disease-specific HRQoL, generic HRQoL, and family functioning in real-world cohort of children with IBD remains insufficiently defined.

    Health-Related quality of life in Russian children with inflammatory bowel disease is comparable across disease types and treatment modalities · 2026 · DOI

  • Background/Aims: The awareness, accessibility, and utilization of transabdominal intestinal ultrasound (IUS) in inflammatory bowel disease (IBD) management from both physicians’ and patients’ perspectives remains unclear in China.

    Integrating perspectives on transabdominal intestinal ultrasound in inflammatory bowel disease management: a nationwide cross-sectional survey of physicians and patients in China · 2026 · DOI

  • Key messagesO_ST_ABSWhat is already known about this topicC_ST_ABSRoutine monitoring of Crohns disease relies on inflammatory markers and conventional reference intervals, but relapse prediction remains difficult, and subtle within-range changes in common blood biomarkers remain poorly characterized.

    Biological drifts within normal ranges allow the detection of Crohn's disease patients at high risk of rehospitalization · 2026 · DOI

  • While gut microbiome dysbiosis is well described in IBD, its functional consequences, particularly microbial immunomodulatory function (MIF) remain poorly defined.

    Microbial Immunomodulatory Function is Altered in Inflammatory Bowel Disease Independent of Microbial Composition · 2026 · DOI

  • Our findings sug- gest that the anti-UC effects of Iso may involve the Nrf2- PTGS2 axis and immune-inflammatory pathways, although direct mechanistic validation remains to be performed.

    Isorhamnetin ameliorates active ulcerative colitis potentially involving the Nrf2-PTGS2 axis: an integrative study from clinical evidence mining to in vivo validation · 2026 · DOI

  • Second, our data suggest that YFB treatment was associated with restoration of LGR5- positive intestinal stem cells and SOX9-positive progeni- tor cells, while concurrently normalizing the aberrant expansion of CHGA-positive enteroendocrine cells—a mechanistic aspect of YFB that has not been previously documented.

    Yiyi Fuzi Baijiang formula protects against DSS-induced colitis by orchestrating the gut barrier-microbiota-metabolism axis · 2026 · DOI

  • Abstract Objectives Exclusive enteral nutrition (EEN) is the first‐line treatment for pediatric Crohn's disease, but its mechanisms of action remain poorly understood.

    Exclusive enteral nutrition containing transforming growth factor‐β improves intestinal barrier function in a colitis mouse model · 2026 · DOI

  • BACKGROUND Appendectomy reduces the occurrence and controls the severity of ulcerative colitis (UC); however, how it exerts these effects remains unclear.

    Contribution of the appendix to ulcerative colitis by supplying pathogenic immunoglobulin G-producing cells · 2026 · DOI

  • However, many proposed biomark- ers—such as von Willebrand factor, VEGF, or circulating adhesion molecules—remain limited by their nature as acute-phase reactants and by the absence of prospective val- idation with thrombotic endpoints in IBD-specific cohorts.

    Molecular determinants of thromboinflammatory activation in inflammatory bowel disease · 2026 · DOI

  • Future work will focus on strategies such as increasing polymer concen- tration, modifying polymer ratios, incorporation of release- retarding agents, or application of additional coating layers to achieve a more controlled and prolonged release profile. Therefore, this represents a limitation of the present study, and further optimisation is warranted. However, the use of a single buffer does not fully replicate the dynamic gastrointestinal transit; it is a limitation of this study. The release profile is in vitro related to prints-only BET (betulinic acid–loaded microspheres), and sec prints (unloaded) have not been evaluated for release.

    Development and Evaluation of Betulinic Acid-Loaded Microspheres for Targeted Treatment in Inflammatory Ulcerative Colitis · 2026 · DOI

  • Background and aims Although vedolizumab (VDZ) serves as a primary biologic for ulcerative colitis (UC), long-term data in Chinese biologic-naïve cohorts and cost-effective prognostic biomarkers remain lacking.

    Vedolizumab in biologic-naïve ulcerative colitis: a multicenter real-world evaluation of clinical benefits and exploratory inflammatory indices · 2026 · DOI

  • Future research should focus on strengthening clinical validation through standardized trial design; formula standardization and quality-marker-based establishing control; optimizing oral bioavailability and colon-targeted exposure; improving experimental reproducibility through harmonization of models, doses, and endpoints; and moving from associative mechanisms to causal validation.

    Gegen Qinlian Decoction, a classic traditional Chinese medicine formula: a potential therapeutic strategy for ulcerative colitis and colorectal cancer · 2026 · DOI

  • Although evidence regarding GQD and its representative bioactive constituents has continued to accumulate, the current evidence base remains largely preclinical and is still insufficient to support definitive clinical translation. Several major limitations to restrict cross-study comparability and clinical continue clinical interpretation, evidence, incomplete formula standardization, heterogeneity in experimental models insufficiently and dosing characterized PK–PD and bioavailability profiles, and limited causal validation of the proposed mechanisms. high-quality insufficient regimens, including 5.1 Strengthening clinical validation through standardized trial design The most important evidence gap remains the lack of highquality clinical studies. Future clinical investigations should adopt multicenter, randomized, double-blind, controlled trial designs with clearly defined patient populations, standardized interventions, and pre-specified outcome measures.

    Gegen Qinlian Decoction, a classic traditional Chinese medicine formula: a potential therapeutic strategy for ulcerative colitis and colorectal cancer · 2026 · DOI

  • More recent research has highlighted the potential influence of ethnic and racial variation on circulating leptin levels; however, the underlying mechanisms remain to be fully elucidated. Studies have demonstrated conflicting findings regarding serum leptin levels and the presence of IBD, with some reporting negative associations and others reporting statistically significant positive associations.

    Serum Leptin, Ghrelin, and IGF-1 Levels and Their Association with Bone Mineral Density in Patients with Ulcerative Colitis · 2026 · DOI

  • The advent of biologic therapies has significantly advanced the treatment of Crohn’s disease (CD), yet their influence on the development of SIBO remains unclear.

    Frequent exposure to biologics is associated with small intestinal bacterial overgrowth in patients with Crohn’s disease: a retrospective case-control study · 2026 · DOI

  • Crohn’s disease and ulcerative colitis belong to chronic inflammatory conditions (IBD) with increasing prevalence. In the Czech Republic, the current prevalence reaches 1%. Both conditions require long-term medical therapy that consists of conventional and advanced drugs (biologics and small molecules). Advanced therapy is more effective and safer compared to conventional drugs and should be preferred in patients with moderate to severe disease. In the Czech Republic, IBD patients with advanced drugs are enrolled into the registry called CREdIT. The proportion of such patients is, however, low compared to most developerd countries in the Europe. On the other hand, the proportsion of patient on long-term systemic steroids is too high, so is the proportion of Crohn’s disease patients treated with aminosalicylates. Therapeutic outcomes in IBD patients can be improved by early initiation of advanced therapy. Key words: inflammatory bowel disease, Crohn’s disease, ulcerative colitis, advanced therapy. Úvod Česká republika patří v současné době k zemím s vysokou prevalencí, Idiopatické střevní záněty (IBD), mezi něž řadíme Crohnovu chorobu která se blíží hodnotě 1 % (1). Základem léčby IBD je medikamentózní (CD) a ulcerózní kolitidu (UC), patří mezi zánětlivá onemocnění trávicí terapie, která doznala zásadních změn v posledních dvou dekádách. trubice se širokým spektrem projevů střevních i mimostřevních. Jejich Klíčovým nástrojem se v současné době stala léčba zahrnující biologispolečnou charakteristikou je komplexní etiopatogeneze, chronický ka (monoklonální protilátky) a malé molekuly, souhrnně označovaná a špatně předvídatelný průběh a celosvětově rostoucí počet pacientů. termínem cílená (ev. inovativní, pokročilá) léčba. Cílená terapie IBD je MUDr. Václav Štěpánek Gastroenterologické oddělení, Nemocnice České Budějovice [email protected] Cit. zkr: Vnitř Lék. 2026;72(4):215-223 Článek přijat redakcí: 27. 4. 2026 Článek přijat po recenzích: 11. 6. 2026 www.casopisvnitrnilekarstvi.cz / Vnitř Lék. 2026;72(4):215-223 / VNITŘNÍ LÉKAŘSTVÍ 216 | HLAVNÍ TÉMA Idiopatické střevní záněty – současný stav v České republice a budoucí perspektivy spojena se zvýšením kvality života pacientů a snížením invalidizující- rurgickou léčbu – v průběhu života je operována nejméně polovina ho potenciálu obou nemocí. V České republice počet takto léčených pacientů s CD a 10–20 % pacientů s UC (4). Nové možnosti přináší pacientů sice narůstá, jejich podíl na celkové populaci nemocných léčba endoskopická, součástí managementu IBD je také léčba nutriční, s IBD je však stále nízký (2). Pracovní skupina pro IBD při České gastrehabilitační a psychologická.

    Inflammatory bowel diseases - current situation in the Czech Republic and future perspectives · 2026 · DOI

  • Betulinic acid (BA) is a naturally occurring pentacyclic triterpenoid present in traditional Chinese medicines used clinically as retention enemas for UC, but its direct effects and mechanisms remain unclear.

    Betulinic Acid Enema Alleviates Colitis by Targeting Vitamin D Receptor to Protect the Intestinal Mucosal Barrier and Modulate Mucosa‐Associated Microbiota · 2026 · DOI

  • There are several existing histopathological indices, but they often encompass caveats such as not primarily having been designed to measure the degree of inflammation, encompassing subjective components with poor intra- and interindividual reproducibility, and requiring expert pathologists who are scarce, thus resulting in extended response times.

    QiC3: A novel automated quantitative immunohistological disease activity index for ileocolonic Crohn's disease and ulcerative colitis · 2026 · DOI

  • Background and AimsPerianal fistulizing Crohns disease (PFCD) is a challenging complication with poorly understood pathogenesis and limited treatment options, largely due to the lack of clinically relevant animal models.

    Novel mouse models for perianal fistulizing Crohns disease reveal therapeutic value of interferon-gamma antagonists · 2026 · DOI

  • Serum gelsolin (GSN) has emerged as a potential inflammatory biomarker, but its dynamic changes and predictive value for mucosal healing have not been systematically investigated.

    Dynamic changes in serum gelsolin combined with clinical parameters to construct a predictive model for mucosal healing in inflammatory bowel disease: A prospective cohort study · 2026 · DOI

  • Fibril-associated collagens with interrupted triple helices (FACIT) are known to regulate ECM assembly and mediate biophysical cues in their microenvironment but remain largely understudied.

    Increased remodeling of type XXII collagen is associated with an inflammatory phenotype in Crohn’s disease · 2026 · DOI

  • Conclusions Despite unequivocal evidence and international guidelines recommending against the routine use of 5-ASA in CD, it remains pervasively prescribed by Chinese clinicians.

    Current status of 5-aminosalicylic acid in Crohn’s disease treatment: a nationwide survey and analysis of perspectives and practice patterns among inflammatory bowel disease physicians · 2026 · DOI

  • While filgotinib (FIL) has shown long-term efficacy in improving disease-specific quality-of-life via Inflammatory Bowel Disease Questionnaire (IBDQ) total scores, its impact on individual bowel/systemic symptoms remains unclear.

    Early symptomatic improvement is informing long-term quality-of-life outcomes with filgotinib treatment in ulcerative colitis: a post-hoc analysis of the SELECTION and SELECTIONLTE trials · 2026 · 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.

    Clinical combination therapy for IBD and promising co-delivery strategies · 2026 · DOI

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91 open questions have been extracted from the limitations and future-work passages of 717 Inflammatory Bowel Disease papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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