Inflammatory Bowel Disease Therapy Research Articles

Real-World Treatment Outcomes Associated With Early Versus Delayed Vedolizumab Initiation in Patients With Ulcerative Colitis.

Patients with ulcerative colitis (UC) typically receive a targeted inflammatory bowel disease therapy after treatment with conventional therapies and after the development of significant morbidity. Evidence suggests that early biologic treatment after diagnosis could improve treatment response and prevent disease complications compared with delayed biologic treatment after conventional therapy. RALEE was a retrospective study using claims data from IBM® MarketScan® Research Databases between January 1, 2016 and December 31, 2019. Adults with UC and at least one claim for vedolizumab were categorized into Early or Delayed Vedolizumab groups according to whether they had received vedolizumab within 30 days of diagnosis or after conventional therapy (5-aminosalicylates, corticosteroids, and immunomodulators), respectively. Treatment response was assessed at 2, 6, and 12 months after vedolizumab treatment initiation and was analyzed with logistic regression (bivariate). At 2 months, Delayed Vedolizumab was associated with significantly higher odds of nonresponse than Early Vedolizumab (odds ratio [OR], 2.509; 95% confidence interval [CI], 1.28-4.90). Delayed Vedolizumab was not significantly associated with odds of nonresponse at 6 months (OR, 1.173; 95% CI, 0.72-1.90) or at 12 months (OR, 0.872; 95% CI, 0.55-1.37). Mean total healthcare costs were similar in the Early Vedolizumab ($6492) and Delayed Vedolizumab ($5897) groups, although there were small differences in costs from different types of claims. Patients who received vedolizumab early after UC diagnosis were less likely to experience nonresponse at 2 months and incurred similar healthcare costs at 12 months compared with patients who received delayed vedolizumab.

Management and outcomes of histoplasmosis in youth with inflammatory bowel disease in an endemic area.

Patients with inflammatory bowel disease (IBD) prescribed immunosuppressive therapies including antitumor necrosis factor (aTNF) therapies are at increased risk of histoplasmosis. We aim to evaluate the presentation, management, and outcomes of youth with IBD and concurrent histoplasmosis. Single center, retrospective review of youth with IBD diagnosed with histoplasmosis from January 12, 2007 to January 1, 2022. Management and outcomes were followed for up to 2 years after diagnosis. Nineteen patients (10 male, median age 16 years, range 8-22) with IBD were diagnosed with histoplasmosis: disseminated (N = 15/19; 79%), pulmonary (N = 3/19; 16%), lymph node (N = 1/19; 5%). At the time of histoplasmosis diagnosis, patients were predominantly receiving aTNF therapy (N = 17/19; 89%, median duration 21.9 months (interquartile range 8.5-52.0). Thirteen (13/19, 68%) patients required hospitalization and 2/19 (11%) required intensive care. All achieved antigen clearance with no recurrences. At the time of histoplasmosis diagnosis, aTNF was stopped in 15/17 (88%) patients and the following IBD therapies were initiated: 5-aminosalicylates (N = 4/19; 21%), 6-mercaptopurine (N = 3/19; 16%), enteral therapy (N = 2/19; 11%), and vedolizumab (N = 2/19; 11%); 6 of 19 (32%) received no IBD therapy and 2 of 19 (11%) patients continued aTNF. During follow-up, 6 of 19 (32%) patients had an emergency department (ED) visit and/or hospitalization for symptoms attributed to active IBD, all of whom had discontinued aTNF; one patient required colectomy. Severe histoplasmosis infection in youth with IBD was rare. IBD treatment was modified by reducing immunosuppression. Histoplasmosis outcomes were favorable, but multiple patients required hospitalization or ED visits for IBD symptoms. The optimal approach to managing IBD during histoplasmosis treatment is challenging and requires further study.

Phase 2 Trial of Anti-TL1A Monoclonal Antibody Tulisokibart for Ulcerative Colitis

BackgroundTulisokibart is a tumor necrosis factor–like cytokine 1A (TL1A) monoclonal antibody in development for the treatment of moderately to severely active ulcerative colitis. A genetic-based diagnostic test was designed to identify patients with an increased likelihood of response.MethodsWe randomly assigned patients with glucocorticoid dependence or failure of conventional or advanced therapies for ulcerative colitis to receive intravenous tulisokibart (1000 mg on day 1 and 500 mg at weeks 2, 6, and 10) or placebo. Cohort 1 included patients regardless of status with respect to the test for likelihood of response. Cohort 2 included only patients with a positive test for likelihood of response. The primary analysis was performed in cohort 1; the primary end point was clinical remission at week 12. Patients with a positive test for likelihood of response from cohorts 1 and 2 were combined in prespecified analyses.ResultsIn cohort 1, a total of 135 patients underwent randomization. A significantly higher percentage of patients who received tulisokibart had clinical remission than those who received placebo (26% vs. 1%; difference, 25 percentage points; 95% confidence interval [CI], 14 to 37; P<0.001). In cohort 2, a total of 43 patients underwent randomization. A total of 75 patients with a positive test for likelihood of response underwent randomization across both cohorts. Among patients with a positive test for likelihood of response (cohorts 1 and 2 combined), clinical remission occurred in a higher percentage of patients who received tulisokibart than in those who received placebo (32% vs. 11%; difference, 21 percentage points; 95% CI, 2 to 38; P=0.02). Among all the enrolled patients, the incidence of adverse events was similar in the tulisokibart and placebo groups; most adverse events were mild to moderate in severity.ConclusionsIn this short-term trial, tulisokibart was more effective than placebo in inducing clinical remission in patients with moderately to severely active ulcerative colitis. (Funded by Prometheus Biosciences, a subsidiary of Merck; ARTEMIS-UC ClinicalTrials.gov number, NCT04996797.)

Healthcare Utilization and Geographic Distribution of Advanced Therapy in Minority Race and Ethnic Groups With Inflammatory Bowel Disease.

Biases in healthcare pose challenges for inflammatory bowel disease (IBD) patients from underrepresented races and ethnicities. Our study aimed to assess the quality of and access to care among underrepresented racial and ethnic populations using a diverse database. We used the OneFlorida Data Trust, representing over half of Florida's population. We performed a retrospective study from 2012 to 2020. Advanced IBD therapies included a prescription of at least 1 biologic agent or tofacitinib. Disease activity markers included C-reactive protein (CRP), hemoglobin (Hgb), albumin, and white blood cell (WBC). Regression analyses compared the rates of medication use, healthcare utilization, and disease severity by race and ethnicity. Geographic distribution of advanced IBD therapy was analyzed at the county level. Our study included 10 578 patients. Hispanic patients utilized more biologics than non-Hispanic White (NHW) patients (odds ratio [OR]: 1.3, P<.0001). Non-Hispanic Black patients utilized more steroids than NHW (OR: 1.2, P=.0004). Hispanics had fewer visits to emergency departments (EDs) and fewer admissions compared with NHW (OR: 0.7 and 0.6, respectively; P<.0001). Non-Hispanic Black patients visited ED more frequently than NHW patients (OR: 1.3, P<.0001). Hispanics had lower disease activity markers than NHW based on CRP (OR: 0.5, P=.005), Hgb (OR: 0.4, P<.0001), albumin (OR: 0.7, P<.0001), and WBC (OR: 0.5, P<.0001). Geographic distribution of advanced IBD therapy showed clustered areas in southern and northern Florida. Our data show an improved access to care pattern in Hispanic patients. However, disparities still exist, and this is evident in the healthcare utilization trends observed among non-Hispanic Black patients.

Diagnosis and Management of Inflammatory Bowel Disease-Associated Spondyloarthritis.

Inflammatory bowel disease (IBD)-associated spondyloarthritis (SpA) is common but remains poorly understood. In this review article, we aimed to provide guidance regarding the diagnosis and management of this condition. For diagnosis of IBD-associated peripheral SpA (IBD-pSpA), we recommend collaboration with rheumatology for incorporation of clinical symptoms, physical examination findings, joint imaging if applicable, and available diagnostic criteria. For the management of IBD-pSpA, we first recommend assessment and treatment of underlying luminal IBD disease activity. We provide guidance regarding positioning of advanced therapies for IBD in patients with IBD-pSpA based on the limited available literature. For diagnosis of IBD-associated axial SpA, we recommend rheumatology referral to make the diagnosis based on incorporation of symptoms, laboratory data, imaging findings (sacroiliitis), and available diagnostic criteria. For the management of axial SpA, we recommend comanagement with rheumatology and use of either antitumor necrosis factor agents or Janus kinase inhibitors, when applicable.

Negatively Charged Thermosensitive Hydrogel Loaded with Pectin Microspheres to Recover the Mucosal Barrier for Ulcerative Colitis Therapy.

Ulcerative colitis (UC), a chronic inflammatory bowel disease, poses a heightened colorectal cancer risk due to persistent mucosal inflammation and barrier dysfunction. In this article, a negatively charged thermosensitive hydrogel loaded with pectin microspheres was used as the enema for UC treatment. Succinic acid was immobilized on poly(ε-caprolactone-co-glycolide)-poly(ethylene glycol)-poly(ε-caprolactone-co-glycolide) (PCLGA-PEG-PCLGA) triblock copolymers to preferentially coat on cationic-inflamed sites via electrostatic interaction for reconstructing the mucosal barrier. Anti-inflammation drug 5-aminosalicylic acid (5-ASA) and curcumin-loaded pectin microspheres (Pec@Cur) were dispersed in the hydrogel for the inflammatory treatment of UC. The thermally sensitive hydrogels were rectally injected into UC model mice. The hydrogel effectively adhered to ulcers and prolonged colon retention, enabling sustained drug release and remarkably relieving the symptoms of colitis. The negatively charged hydrogel exhibited excellent significance in the UC treatment.

Harms with placebo in trials of biological therapies and small molecules as induction therapy in inflammatory bowel disease: a systematic review and meta-analysis

Randomised placebo-controlled trials are the gold standard to assess novel drugs in ulcerative colitis and Crohn's disease. However, there might be risks associated with receiving placebo. We aimed to examine the harms associated with receiving placebo in trials of licensed biologics and small molecules for the induction of remission in ulcerative colitis and luminal Crohn's disease in a meta-analysis. We performed a systematic review and meta-analysis. We searched MEDLINE, Embase, Embase Classic, and the Cochrane Central Register of Controlled Trials from database inception to May 30, 2024, for randomised placebo-controlled trials of licensed biologics and small molecules for induction of remission in adults (≥18 years) with moderately to severely active ulcerative colitis or luminal Crohn's disease reporting data on adverse events over a minimum treatment period of 4 weeks. There were no prespecified study exclusion criteria. We extracted summary data and pooled data using a random-effects model for any treatment-emergent adverse event, any drug-related adverse event, infection, worsening of inflammatory bowel disease (IBD) activity, withdrawal due to adverse events, serious adverse events, serious infection, serious worsening of IBD activity, or venous thromboembolic events (VTEs), reporting relative risks (RRs) with 95% CIs. The protocol for this meta-analysis was registered with PROSPERO (CRD42024527341). The search identified 10 826 citations, of which 47 trials including 20 987 patients (14 267 [68·0%] receiving active drug and 6720 [32·0%] receiving placebo) were eligible. The risk of any treatment-emergent adverse event was no different with active drug than with placebo (7660/14 267 [53·7%] patients on active drug vs 3758/6720 [55·9%] on placebo; RR 0·97, 95% CI 0·94-1·00; I2 =36%). However, the risks of worsening of IBD activity (563/13 473 [4·2%] vs 530/6252 [8·5%]; 0·48, 0·40-0·59; I2 =54%), withdrawal due to adverse event (401/13 363 [3·0%] vs 299/6267 [4·8%]; 0·62, 0·48-0·79; I2 =46%), serious adverse event (682/14 267 [4·8%] vs 483/6720 [7·2%]; 0·69, 0·59-0·80; I2 =30%), serious infection (140/14 194 [1·0%] vs 91/6647 [1·4%]; 0·67, 0·50-0·89; I2 =0%), serious worsening of IBD activity (187/11 271 [1·7%] vs 189/5056 [3·7%]; 0·45, 0·34-0·60; I2 =27%), or VTEs (13/7542 [0·2%] vs 12/2981 [0·4%]; 0·45, 0·21-0·94; I2 =0%) were all significantly lower with active drug than placebo. Numbers needed to treat with active drug to avoid these potentially serious adverse events ranged from 23 for worsening of IBD activity to 452 for VTEs. 27 randomised controlled trials were judged as low risk of bias across all domains. Patients with moderately to severely active IBD receiving placebo are more likely to experience significant worsening of IBD activity and some serious adverse events, which might relate to a reduction in risk of these events with active drug. Patients should be counselled about these potential harms, and alternative trial designs to mitigate these harms should be considered. None.

Harms with placebo in trials of biological therapies and small molecules as maintenance therapy in inflammatory bowel disease: a systematic review and meta-analysis

Randomised placebo-controlled trials for the induction of inflammatory bowel disease (IBD) remission involve potential harms to those receiving placebo. Whether these harms are also apparent with placebo during maintenance of remission trials in IBD is unclear. We aimed to examine the potential harms associated with receiving placebo in trials of licensed biologics and small molecules for maintenance of remission of ulcerative colitis and luminal Crohn's disease in a meta-analysis. We performed a systematic review and meta-analysis. We searched several medical literature databases including MEDLINE (from Jan 1, 1946, to May 31, 2024), Embase and Embase Classic (Jan 1, 1947, to May 31, 2024), and the Cochrane Central Register of Controlled Trials from database inception to May 31, 2024, for randomised placebo-controlled trials of licensed biologics and small molecules for maintenance of remission in adults with IBD reporting data on adverse events over a period of 20 weeks or more. There were no language restrictions or prespecified exclusion criteria. We extracted summary data and pooled data using a random-effects model for any treatment-emergent adverse event, drug-related adverse event, infection, worsening of IBD activity, withdrawal due to adverse events, serious adverse events, serious infection, serious worsening of IBD activity, or venous thromboembolic events, reporting relative risks (RRs) for placebo versus active drug with 95% CIs for each outcomes. The protocol for this meta-analysis was registered with PROSPERO (CRD42024542624). Our search identified 10 826 citations, of which 45 trials including 16 562 patients (10 319 [62·3%] receiving active drug and 6243 [37·7%] placebo) were eligible. The risks of any treatment-emergent adverse event (7297/9546 [76·4%] patients on active drug vs 4415/5850 [75·5%] on placebo; RR 1·01, 95% CI 0·99-1·04; I2 =47%), serious infection (260/10 242 [2·5%] vs 155/6149 [2·5%]; 0·97, 0·79-1·19; I2 =0%), or venous thromboembolic event (12/4729 [0·3%] vs 9/2691 [0·3%]; 0·72, 0·31-1·66; I2 =0%) were not significantly lower with active drug than placebo. The risks of any infection (3208/8038 [39·9%] vs 1713/4809 [35·6%]; 1·14, 1·05-1·23; I2 =60%) or any drug-related adverse event (1094/2997 [36·5%] vs 609/1950 [31·2%]; 1·24, 1·02-1·50; I2 =75%) were higher with active drug than placebo. However, the risks of any worsening of IBD activity (1038/8090 [12·8%] vs 1181/5191 [22·8%]; 0·58, 0·52-0·64; I2 =40%), any withdrawal due to adverse events (610/10 282 [5·9%] vs 561/6207 [9·0%]; 0·71, 0·60-0·84; I2 =43%), any serious adverse events (1066/10 292 [10·4%] vs 742/6198 [12·0%]; 0·85, 0·77-0·94; I2 =17%), or any serious worsening of IBD activity (101/5707 [1·8%] vs 143/3640 [3·9%]; 0·55, 0·42-0·71; I2 =0%) were lower with active drug than placebo. 21 randomised controlled trials were judged as low risk of bias across all domains. In maintenance of remission trials in IBD, placebo was associated with some clinically significant potential harms. Patients should be counselled about these before participating in clinical trials and consideration given to alternative designs to test novel drugs in IBD. None.

Functional Ginger-Derived Extracellular Vesicles-Coated ZIF-8 Containing TNF-α siRNA for Ulcerative Colitis Therapy by Modulating Gut Microbiota.

Tumor necrosis factor-α (TNF-α) plays a causal role in the pathogenesis of ulcerative colitis (UC), and anti-TNF-α siRNA shows great promise in UC therapy. However, delivering siRNA with site-targeted stability and therapeutic efficacy is still challenging due to the complex and dynamic intestinal microenvironment. Here, based on the functional plant-derived ginger extracellular vesicles (EVs) and porous ZIF-8 nanoparticles, we propose a novel TNF-α siRNA delivery strategy (EVs@ZIF-8@siRNA) for UC targeted therapy. Ginger EVs show strong colon and macrophage targeting, as well as robust resistance to acidic degradation in the stomach. Moreover, 6-shogaol in ginger-derived EVs displays anti-inflammatory effects, which enhance the treatment efficiency by cooperation with TNF-α siRNA. In vitro experiments reveal that ZIF-8 nanoparticles have high TNF-α siRNA loading capacity and promote siRNA escape from cellular lysosomes. In vivo experiments show that the TNF-α level is reduced more significantly in colonic tissue than other nontargeted inflammation related factors, showing a good targeting of this composite nanoparticle. Furthermore, gut microbiota sequencing results demonstrate that the nanoparticles can promote intestinal barrier repair by regulating the intestinal microbial balance and restoring the intestinal health of UC mice. Therefore, the developed EVs@ZIF-8@siRNA nanoparticles may represent a novel colon-targeted oral drug, providing a promising therapeutic strategy for UC therapy.

Christensenella minuta protects and restores intestinal barrier in a colitis mouse model by regulating inflammation

Christensenella minuta DSM 22607 has recently been suggested as a potential microbiome-based therapy for inflammatory bowel disease (IBD) because it displays strong anti-inflammatory effects both in vitro and in vivo. Here, we aimed to decipher the mechanism(s) underlying the DSM 22607-mediated beneficial effects on the host in a mouse model of chemically induced acute colitis. We observed that C. minuta plays a key role in the preservation of the epithelial barrier and the management of DNBS-induced inflammation by inhibiting interleukin (IL)-33 and Tumor necrosis factor receptor superfamily member 8 (Tnfrsf8) gene expression. We also showed that DSM 22607 abundance was positively correlated with Akkermansia sp. and Dubosiella sp. and modulated microbial metabolites in the cecum. These results offer new insights into the biological and molecular mechanisms underlying the beneficial effects of C. minuta DSM 22607 by protecting the intestinal barrier integrity and regulating inflammation.

The Role of Diet in Inflammatory Bowel Disease Onset, Disease Management, and Surgical Optimization.

The concept of using diet as therapy in inflammatory bowel disease is of interest to clinicians and patients. Once considered to play a minor role, diet is now known to not only affect disease onset but may also serve as a therapeutic tool for inducing and maintaining remission and improving surgical outcomes. Further research is needed to fully elucidate how, when, and in whom diet therapies may be best applied to improve clinical and disease outcomes. The aim of this review was to summarize current research findings and serve as a tool to help facilitate patient-clinician conversations.

Characteristics of Mucosa-Associated Microbiota in Ulcerative Colitis Patients with 5-Aminosalicylic Acid Intolerance.

5-Aminosalicylic acid (5-ASA) is a first-line therapy for ulcerative colitis (UC). This study examined the mucosa-associated microbiota (MAM) in UC patients, distinguishing between those who were 5-ASA tolerant and intolerant. Brushing samples were collected from the sigmoid and ileal end of patients with UC during endoscopic procedures. The samples were profiled by using the Illumina MiSeq platform. The V3-V4 regions of the 16S rRNA gene (460 bp) were amplified by using tailed PCR. A total of 15 patients with 5-ASA intolerance, 38 patients with 5-ASA tolerance, and 19 healthy controls were recruited in this study. The α-diversity indices were remarkably different among the three groups in the ileum mucosa but not in the sigmoid colon. In the ileum mucosa, Alistipes, Ruminococcaceae, and Odoribacter were less abundant in the 5-ASA-intolerant group than in the control and 5-ASA-tolerant groups. On the contrary, Merdibacter, Brevundimonas, and Porphyromonas were more abundant in the 5-ASA-intolerant group than in other groups. The present study showed that the changes in MAM were characterized by a decrease in mucoprotective bacteria rather than an increase in harmful bacteria.

Reactive Oxygen Species Triggered Cleavage of Thioketal‐Containing Supramolecular Nanoparticles for Inflammation‐Targeted Oral Therapy in Ulcerative Colitis

AbstractCombating reactive oxygen species (ROS) and targeted drug delivery to inflammatory sites are considered effective therapeutic strategies for ulcerative colitis (UC), a refractory chronic inflammatory disease. Herein, a ROS‐responsive thioketal (TK) crosslinked cyclodextrin metal‐organic framework (TCOF) is fabricated, to which a non‐ROS‐sensitive vector, sulfur substituted by carbon chain‐crosslinked cyclodextrin metal‐organic framework (CCOF) is parallelly designed as ROS negative reference. Dexamethasone (DEX) loaded in TCOF (TCD) and CCOF (CCD) are investigated to demonstrate the advantages of precision medicine for UC. After the ROS‐induced collapse of nanoparticles, TCD selectively triggered the release of DEX. Moreover, TCD effectively protected cells from oxidative stress damage and reduced inflammation levels in vitro. Remarkably, the TK group of TCD is oxidatively broken by consuming ROS at the inflammatory site, exposing the thiol group to mucosal adhesion, which enhances the retention of TCD at colons. In vivo studies of UC treatment reveals that oral administration of TCD demonstrated excellent inflammation‐targeting properties, remarkably attenuated oxidative stress, and ameliorated both acute and chronic colitis compared to CCD. Furthermore, TCD exhibits an excellent safety profile in mice. These results instill confidence in advancing targeted drug delivery and precision therapy for UC.

Systematic review with meta-analysis of the effectiveness of subcutaneous biologics versus intravenous biologics in inflammatory bowel diseases

Background Biologic therapies are commonly used for inflammatory bowel disease (IBD) patients. Multiple biologic medicines can now be given both intravenously and subcutaneously. The different administration routes present provide different advantages regarding dose escalation, healthcare resource utilisation, pharmacokinetics, convenience and safety. Comparator effectiveness studies between intravenous and subcutaneous administration are lacking. Aim Our primary outcome was to compare the effectiveness between intravenous and subcutaneous biologics in rates of clinical remission. Methods We performed a systematic review and meta-analysis to include all relevant articles from MEDLINE (Ovid), EMBASE, PubMed and Cochrane Central Register of Controlled Trials from 1 January 2003 to 28 January 2024. Studies that compared intravenous and subcutaneous administration of the same biologic therapy in IBD patients and reported effectiveness outcomes were included. This study was registered on PROSPERO (CRD42023442675). Results Twenty studies met the inclusion criteria for the systematic review. Nine vedolizumab cohort studies were meta-analysed for clinical remission and no difference was found in clinical remission rates between intravenous and subcutaneous administration (relative risk = 0.99; 95% confidence interval: 0.88, 1.11). Six infliximab cohort studies were meta-analysed for clinical remission and no difference was found in clinical remission rates between intravenous and subcutaneous administration (relative risk = 0.91; 95% confidence interval: 0.77, 1.08). Conclusions Our findings in the first meta-analysis comparing the effectiveness of intravenous and subcutaneous biologic therapies in IBD suggest there is no difference in the effectiveness between these two administration routes. However, further high-quality studies, particularly head-to-head studies are needed to confirm this finding.

Treatment Related Adverse Events and Monitoring of Patients Receiving Biologic or Small Molecule Therapy for Inflammatory Bowel Disease

Treatment Related Adverse Events and Monitoring of Patients Receiving Biologic or Small Molecule Therapy for Inflammatory Bowel Disease

Closed-loop theranostic microgels for immune microenvironment modulation and microbiota remodeling in ulcerative colitis

Inflammatory bowel disease (IBD) is characterized by the upregulation of reactive oxygen species (ROS) and dysfunction of gut immune system, and microbiota. The conventional treatments mainly focus on symptom control with medication by overuse of drugs. There is an urgent need to develop a closed-loop strategy that combines in situ monitoring and precise treatment. Herein, we innovatively designed the ‘cluster munition structure’ theranostic microgels to realize the monitoring and therapy for ulcerative colitis (a subtype of IBD). The superoxide anion specific probe (tetraphenylethylene-coelenterazine, TPC) and ROS-responsive nanogels consisting of postbiotics urolithin A (UA) were loaded into alginate and ion-crosslinked to obtain the theranostic microgels. The theranostic microgels could be delivered to the inflammatory site, where the environment-triggered breakup of the microgels and release of the nanogels were achieved in sequence. The TPC-UA group had optimal results in reducing inflammation, repairing colonic epithelial tissue, and remodeling microbiota, leading to inflammation amelioration and recovery of tight junction between the colonic epithelium, and maintenance of gut microbiota. During the recovery process, the local chemiluminescence intensity, which is proportional to the degree of inflammation, was gradually inhibited. The cluster munition of theranostic microgels displayed promising outcomes in monitoring inflammation and precise therapy, and demonstrated the potential for inflammatory disease management.

Lactic Acid Bacteria-Gut-Microbiota-Mediated Intervention towards Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD), encompassing ulcerative colitis (UC) and Crohn's disease (CD), arises from intricate interactions involving genetics, environment, and pharmaceuticals with an ambiguous pathogenic mechanism. Recently, there has been an increasing utilization of lactic acid bacteria (LAB) in managing IBD, attributed to their ability to enhance intestinal barrier function, mitigate inflammatory responses, and modulate gut microbiota. This review initiates by elucidating the pathogenesis of IBD and its determinants, followed by an exploration of the mechanisms underlying LAB therapy in UC and CD. Special attention is directed towards their influence on intestinal barrier function and homeostasis regulated by gut microbiota. Furthermore, the review investigates the complex interplay among pivotal gut microbiota, metabolites, and pathways associated with inflammation. Moreover, it underscores the limitations of LAB in treating IBD, particularly in light of their varying roles in UC and CD. This comprehensive analysis endeavors to offer insights for the optimized application of LAB in IBD therapy.

Lactobacillus gasseri ATCC33323 affects the intestinal mucosal barrier to ameliorate DSS-induced colitis through the NR1I3-mediated regulation of E-cadherin.

Inflammatory bowel disease (IBD) is an immune system disorder primarily characterized by colitis, the exact etiology of which remains unclear. Traditional treatment approaches currently yield limited efficacy and are associated with significant side effects. Extensive research has indicated the potent therapeutic effects of probiotics, particularly Lactobacillus strains, in managing colitis. However, the mechanisms through which Lactobacillus strains ameliorate colitis require further exploration. In our study, we selected Lactobacillus gasseri ATCC33323 from the intestinal microbiota to elucidate the specific mechanisms involved in modulation of colitis. Experimental findings in a DSS-induced colitis mouse model revealed that L. gasseri ATCC33323 significantly improved physiological damage in colitic mice, reduced the severity of colonic inflammation, decreased the production of inflammatory factors, and preserved the integrity of the intestinal epithelial structure and function. It also maintained the expression and localization of adhesive proteins while improving intestinal barrier permeability and restoring dysbiosis in the gut microbiota. E-cadherin, a critical adhesive protein, plays a pivotal role in this protective mechanism. Knocking down E-cadherin expression within the mouse intestinal tract significantly attenuated the ability of L. gasseri ATCC33323 to regulate colitis, thus confirming its protective role through E-cadherin. Finally, transcriptional analysis and in vitro experiments revealed that L. gasseri ATCC33323 regulates CDH1 transcription by affecting NR1I3, thereby promoting E-cadherin expression. These findings contribute to a better understanding of the specific mechanisms by which Lactobacillus strains alleviate colitis, offering new insights for the potential use of L. gasseri as an alternative therapy for IBD, particularly in dietary supplementation.

Advancements in Inflammatory Bowel Disease Management: From Traditional Treatments to Monoclonal Antibodies and Future Drug Delivery Systems.

Inflammatory bowel disease (IBD) is a chronic gastrointestinal inflammatory disorder with two main subtypes: ulcerative colitis (UC) and Crohn's disease (CD). The pathogenesis involves genetic predisposition, dysbiosis, and immune dysregulation. Complications include perianal lesions, strictures, fistulas, perforations, and an increased risk of colon cancer. Clinical classification ranges from mild to fulminant and recurrent disease, with common symptoms such as abdominal discomfort, rectal bleeding, diarrhea, and weight loss. Extraintestinal manifestations include arthritis, erythema nodosum, pyoderma gangrenosum, and uveitis. Conventional treatments using aminosalicylates, corticosteroids, and immunomodulators have limitations. Biologics, introduced in the 1990s, offer improved efficacy and specificity, targeting factors like TNF-α, integrins, and cytokines. Monoclonal antibodies play a crucial role in IBD management, aiming to reduce relapses, hospitalizations, and surgeries. In conclusion, this review is aimed at summarizing the latest knowledge, advantages, and drawbacks of IBD therapies, such as small molecules, biologics, and monoclonal antibodies, to provide a basis for further research in the IBD field.

Intestinal and hepatic benefits of BBR-EVO on DSS-induced experimental colitis in mice.

Ulcerative colitis (UC), characterized by disrupted intestinal barrier integrity and chronic inflammation, was modeled in mice via dextran sulfate sodium (DSS) induction. This study explored the therapeutic potential of berberine-evodiamine (BBR-EVO), bioactive components of the traditional Chinese medicine Yulian decoction, in DSS colitis. BBR-EVO intervention ameliorated weight loss, diarrhea, colonic shortening, and histopathological damage in colitic mice. The substance increased antioxidant activity while reducing high levels of pro-inflammatory cytokines in the colon, including as TNF-α, IL-1β, and IL-6. BBR-EVO inhibited the DSS-induced decrease in the tight junction proteins ZO-1 and occludin, according to immunohistochemistry. 16S rRNA sequencing demonstrated BBR-EVO partially attenuated DSS-elicited intestinal dysbiosis, reducing opportunistic pathogens and restoring diminished beneficial taxa. Critically, BBR-EVO alleviated secondary hepatic injury in colitic mice, mitigating immune cell infiltration, oxidative stress, cytokine production, and ultrastructural damage, likely by beneficially modulating gut-liver crosstalk. This study reveals BBR-EVO, derived from a traditional Chinese medicine, confers multi-target protective effects in experimental colitis and associated hepatic pathology, warranting further evaluation as a potential therapy for inflammatory bowel diseases like UC. The mechanisms may involve simultaneous augmentation of intestinal barrier integrity, inhibition of inflammation, microbiota regulation, and gut-liver axis optimization.