Inflammatory Bowel Disease Phenotype Research Articles

Excessive nucleic acid R-loops induce mitochondria-dependent epithelial cell necroptosis and drive spontaneous intestinal inflammation.

Oxidative stress, which can be activated by a variety of environmental risk factors, has been implicated as an important pathogenic factor for inflammatory bowel disease (IBD). However, how oxidative stress drives IBD onset remains elusive. Here, we found that oxidative stress was strongly activated in inflamed tissues from both ulcerative colitis patients and Crohn's disease patients, and it caused nuclear-to-cytosolic TDP-43 transport and a reduction in the TDP-43 protein level. To investigate the function of TDP-43 in IBD, we inducibly deleted exons 2 to 3 of Tardbp (encoding Tdp-43) in mouse intestinal epithelium, which disrupted its nuclear localization and RNA-processing function. The deletion gave rise to spontaneous intestinal inflammation by inducing epithelial cell necroptosis. Suppression of the necroptotic pathway with deletion of Mlkl or the RIP1 inhibitor Nec-1 rescued colitis phenotypes. Mechanistically, disruption of nuclear TDP-43 caused excessive R-loop accumulation, which triggered DNA damage and genome instability and thereby induced PARP1 hyperactivation, leading to subsequent NAD+ depletion and ATP loss, consequently activating mitochondrion-dependent necroptosis in intestinal epithelial cells. Importantly, restoration of cellular NAD+ levels with NAD+ or NMN supplementation, as well as suppression of ALKBH7, an α-ketoglutarate dioxygenase in mitochondria, rescued TDP-43 deficiency-induced cell death and intestinal inflammation. Furthermore, TDP-43 protein levels were significantly inversely correlated with γ-H2A.X and p-MLKL levels in clinical IBD samples, suggesting the clinical relevance of TDP-43 deficiency-induced mitochondrion-dependent necroptosis. Taken together, these findings identify a unique pathogenic mechanism that links oxidative stress to intestinal inflammation and provide a potent and valid strategy for IBD intervention.

Is the Mediterranean Diet in Inflammatory Bowel Diseases Ready for Prime Time?

The rising incidence of inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), specifically in the developing world, suggests an important environmental effect. Amongst environmental influences, dietary factors, particularly the adoption of a westernized diet, have been specifically noticed. In contrast, the Mediterranean diet (MED), characterized by high intake of fruits, vegetables, whole grains, legumes, nuts, olive oil, and moderate consumption of animal and ultra processed foods, has shown potential positive effects in IBD. Here we conducted a narrative review focusing on the evidence regarding the role of MED in IBD prevention and management. Epidemiological studies suggest inverse association of MED with CD development. Furthermore, adherence to MED has been associated with clinical improvement in active CD and maintenance of lower levels of inflammatory markers in UC, along with improved quality of life and lower mortality rates in IBD patients. Mechanistically, MED promotes a diverse and beneficial gut microbiota, possesses anti-inflammatory properties through polyphenols and dietary fats, and may modulate oxidative stress. In clinical practice, MED may be adapted to diverse disease phenotypes and cultural preferences, and is a sustainable, easy to maintain dietary approach. Current evidence may support the integration of MED into clinical practice in IBD care. In future research, the efficacy of MED in specific IBD phenotypes should be assessed.

Bacteroides acidifaciens and its derived extracellular vesicles improve DSS-induced colitis

Introduction“Probiotic therapy” to regulate gut microbiota and intervene in intestinal diseases such as inflammatory bowel disease (IBD) has become a research hotspot. Bacteroides acidifaciens, as a new generation of probiotics, has shown beneficial effects on various diseases.MethodsIn this study, we utilized a mouse colitis model induced by dextran sodium sulfate (DSS) to investigate how B. acidifaciens positively affects IBD. We evaluated the effects ofB. acidifaciens, fecal microbiota transplantation, and bacterial extracellular vesicles (EVs) on DSS-induced colitis in mice. We monitored the phenotype of mouse colitis, detected serum inflammatory factors using ELISA, evaluated intestinal mucosal barrier function using Western blotting and tissue staining, evaluated gut microbiota using 16S rRNA sequencing, and analyzed differences in EVs protein composition derived from B. acidifaciens using proteomics to explore how B. acidifaciens has a positive impact on mouse colitis.ResultsWe confirmed that B. acidifaciens has a protective effect on colitis, including alleviating the colitis phenotype, reducing inflammatory response, and improving intestinal barrier function, accompanied by an increase in the relative abundance of B. acidifaciens and Ruminococcus callidus but a decrease in the relative abundance of B. fragilis. Further fecal bacterial transplantation or fecal filtrate transplantation confirmed the protective effect of eosinophil-regulated gut microbiota and metabolites on DSS-induced colitis. Finally, we validated that EVs derived from B. acidifaciens contain rich functional proteins that can contribute to the relief of colitis.ConclusionTherefore, B. acidifaciens and its derived EVs can alleviate DSS-induced colitis by reducing mucosal damage to colon tissue, reducing inflammatory response, promoting mucosal barrier repair, restoring gut microbiota diversity, and restoring gut microbiota balance in mice. The results of this study provide a theoretical basis for the preclinical application of the new generation of probiotics.

The Role of Platelets and von Willebrand Factor in the Procoagulant Phenotype of Inflammatory Bowel Disease.

Although the risk of thrombosis is well documented for inflammatory bowel disease [IBD] patients, the underlying pathological mechanism seems to be different from other thrombotic conditions. Determining the factors responsible for the increased risk of thrombosis in IBD would help to improve the management of this frequent complication. We studied the interplay between platelets, coagulation, and von Willebrand factor [VWF] in 193 IBD patients and in experimental models [acute and chronic] of colitis in wild-type and VWF-deficient mice. We found a platelet-dependent increase in thrombin generation in IBD patients and in our mouse model of colitis. Agglutinated platelets were present in the blood of patients and mice. Interestingly, we observed not only a significant increase in total VWF antigen, but we were also able to detect the presence of active VWF [VWF in its platelet-binding conformation; 3.2 ± 2.7 μg/mL] in the plasma of 30% of all IBD patients. In healthy controls, active VWF levels were <0.3 μg/mL. This led us to further explore experimental colitis in VWF-deficient mice and we observed that these mice were protected against the procoagulant state triggered by the colitis. Unexpectedly, these mice also showed a significant worsening of colitis severity in both acute and chronic models. Platelets and VWF [including its active form] appear to be central players in the procoagulant phenotype in IBD. We observed that the role of VWF in haemostasis differs from its role in colonic tissue healing, potentially opening new therapeutic avenues for a life-threatening complication in IBD patients.

Diagnostic utility, disease activity, and disease phenotype correlation of serum ASCA, pANCA, and PR3-ANCA in pediatric inflammatory bowel disease

ObjectiveThis study aimed to evaluate the diagnostic utility, disease activity, and phenotypic association of serum anti-Saccharomyces cerevisiae antibody (ASCA), perinuclear anti-neutrophil cytoplasmic antibody (pANCA), PR3-ANCA, and MPO-ANCA in pediatric patients with inflammatory bowel disease (IBD). MethodsPediatric patients diagnosed with IBD were recruited and classified as Crohn's disease (CD), ulcerative colitis (UC), and IBD-unclassified (IBD-U) through full investigation. The Paris classification was used to evaluate disease phenotypes of pediatric CD and UC. ResultsIn all, 229 pediatric patients with IBD (CD 147, UC 53, IBD-U 29) were included. The ASCA IgG seropositivity significantly differed among the three groups (CD 75.4%, UC 17.5%, and IBD-U 60.0%; p < 0.001). PR3-ANCA positive rates were the highest in UC (24.0%), followed by IBD-U (17.6%), and none in CD (p = 0.002); pANCA-positive rates were higher in IBD-U (33.6%), followed by UC (28.0%) than in CD (1.4%) (p < 0.001). Regarding disease phenotype, perianal disease revealed higher serum ASCA IgG titers (median 36.7 U/mL in P1 vs. 25.2 U/mL in P0, p = 0.019). Serum ASCA IgG and IgA cutoff values to distinguish CD were 32.7 (U/mL) and 11.9 (U/mL), respectively, with a specificity of 80.0%. ConclusionSerological biomarkers of ASCA IgG and IgA were effective for differentiating CD in pediatric IBD patients, and serum pANCA and PR3-ANCA, but not MPO-ANCA, were effective in distinguishing UC and IBD-U. Furthermore, measuring serological titers of ASCA IgG and IgA may help differentiate CD and evaluate the disease activity and phenotype of pediatric IBD in practice.

Therapeutic Granulomonocytapheresis as a Non-pharmacologic Treatment Option for Inflammatory Bowel Disease: Efficacy Reports on a Wide Age Range and Disease Profile.

The major phenotypes of inflammatory bowel disease(IBD) include ulcerative colitis (UC) and Crohn's disease (CD), which cause debilitating symptoms, including bloody diarrhea, abdominal discomfort, and fever. Patients require life-long immunosuppressive medications, which cause adverse side effects as additional morbidity factors. However, IBD is initiated and perpetuated by inflammatory cytokines, and given that in patients with IBDmyeloid lineage leukocytes are elevated with activation behaviorand release inflammatory cytokines, selective depletion of elevated granulocytes and monocytes by granulomonocytapheresis is a relevant therapeutic option for IBD patients. Therefore, a column filled with specially designed beads as granulomonocytapheresiscarriers for selective adsorption of myeloid lineage leukocytes (Adacolumn) has been applied to treat patients with active IBD. Patients receive up to 10 granulomonocytapheresis sessions at one or two sessions per week. During each session, the carriers adsorb up to 60% of the myeloid leukocytes from the blood that passes through the granulomonocytapheresis column. Efficacy rates in the UC setting have been as high as 85% in steroid-naïve patients, and 100% in drug-naïve, first-episode cases, but patients with a long duration of active IBD and extensive colonic lesions that have become refractory to pharmacological treatmenthave not responded well. However, granulomonocytapheresis has a favorable safety profile. Given that immunosuppressive medications used to treat IBDpotentially may increase the risk of severe viral infection, non-drug granulomonocytapheresisshould be a favorable treatment strategy. Further, by targeting granulomonocytapheresisto patients with background features and identifying a patient as a likely responder, futile use of medical resources is avoided.

Growth hormone use in pediatric inflammatory bowel disease.

Impaired linear growth is a known complication of pediatric inflammatory bowel disease (IBD), but theuse of growth hormone (GH) in this population is not well-described. The primary aim of this study is to determine whether growth hormone use in pediatric IBD leads to improved height outcomes. This was a retrospective chart review of patients with IBD aged 0-21 years followed at a single center between 2018 and 2021 treated with at least 1 year of GH. Records collected included demographics, IBD phenotype, IBD disease activity scores, medications, weight z-score, height z-score, bone age, and details of GH therapy including testing for GH deficiency. The primary outcome measure was change in height z-score after 1 year of GH treatment. Forty-six patients were identified and 18 were excluded. Of the 28 patients included (7 female; 25.0 %), 26 (92.9 %) had a diagnosis of Crohn's disease (CD) and 2 (7.1 %) had ulcerative colitis (UC). The mean (SD) age at GH initiation was 9.6 (3.4) years. Among all participants, there was a significant mean difference in height z-score from baseline to 1 year on therapy (-2.25 vs.-1.50, respectively; difference, 0.75; 95 % CI, 0.56 to 0.94; p<0.001). Among the 19 subjects thatcompleted GH therapy there was a significant mean difference between baseline and final height z-scores (-2.41vs.-0.77, respectively; difference, 1.64; 95 % CI, 1.30 to 1.98; p<0.001). GH use was associated with improved height outcomes. The pediatric IBD patients in this cohort had significant improvements in height z-scores both after one year on therapy and at completion of GH therapy.

Adropin deficiency worsens TNBS-induced colitis

The aim of this study was to describe the effects of adropin deficiency on the distribution, phenotype and pathological phenotype of macrophages in colonic and mesenteric tissues of AdrKO (Enho−/−) mice, so as to explore the mechanism of adropin deficiency in spontaneous and experimental colitis. In this study, RNA-seq and metabonomics were used to screen the regulatory mechanism of adropin on the phenotypic transformation of macrophages. We found that adropin levels in active UC patients were significantly lower than those in normal subjects and remission UC patients, and at the same time, a large number of proinflammatory M1-type macrophages were infiltrated in the mesenteric tissue of colonic tissues from UC and CD patients. At the same time, spontaneous colitis occurred in Enho-/- (adropin-deficient)C57BL/6 mice, and there was an imbalance of M2 → M1 polarization of macrophages in colon and mesentery of Enho-/- mice. In vivo, it has showed that adropin deficiency could exacerbate the pathological phenotype of colitis induced by TNBS. In vitro, adropin was used to intervene RAW264.7 macrophages, and then combined analysis of RNA-seq and metabolomics demonstrated that adropin regulated lipid metabolism of macrophages through PPARγ, thus promoting the repolarization of macrophages from M1 to M2. Adropin deficiency led to an imbalance in the phenotypic distribution of macrophages infiltrating the colon and mesenteric tissues, namely, an increase in M1 type, which led to the occurrence and development of colitis.

The dual lipid desaturase/hydroxylase DEGS2 controls phytoceramide levels necessary to counter intestinal inflammation.

Intestinal immunity is dependent on barrier function to maintain quiescence. The mechanisms for the maintenance of this barrier are not fully understood. Delta 4-desaturase, sphingolipid 2 (DEGS2) is a lipid desaturase and hydroxylase that catalyzes the synthesis of ceramide and phytoceramide from dihydroceramide. Using a forward genetic approach, we found and validated a mutation in Degs2 as causative of increasing susceptibility to colitis and altering the phytoceramide balance in the colon. DEGS2 is expressed in the intestinal epithelium, and the colitis phenotype is dependent on the non-hematopoietic compartment of the mouse. In the absence of DEGS2, the colon lacks phytoceramides and accumulates large amounts of the precursor lipid dihydroceramide. In response to dextran sodium sulfate (DSS)-induced colitis, colonic epithelial cells in DEGS2-deficient mice had increased cell death and decreased proliferation compared to those in wild-type mice. These findings demonstrate that DEGS2 is needed to maintain epithelial integrity, protect against DSS-induced colitis and maintain lipid balance in vivo.

A target-based discovery from a parasitic helminth as a novel therapeutic approach for autoimmune diseases

Regulatory T cells (Tregs) can alleviate the development of autoimmune and inflammatory diseases, thereby proposing their role as a new therapeutic strategy. Parasitic helminths have co-evolved with hosts to generate immunological privilege and immune tolerance through inducing Tregs. Thus, constructing a "Tregs-induction"-based discovery pipeline from parasitic helminth is a promising strategy to control autoimmune and inflammatory diseases. The gel filtration chromatography and reverse-phase high-performance liquid chromatography (RP-HPLC) were used to isolate immunomodulatory components from the egg extracts of Schistosoma japonicum. The extracted peptides were evaluated for their effects on Tregs suppressive functions using flow cytometry, ELISA and T cell suppression assay. Finally, we carried out colitis and psoriasis models to evaluate the function of Tregs induced by helminth-derived peptide invivo. Here, based on target-driven discovery strategy, we successfully identified a small 3kDa peptide (SjDX5-53) from egg extracts of schistosome, which promoted both human and murine Tregs production. SjDX5-53 presented immunosuppressive function by arresting dendritic cells (DCs) at an immature state and augmenting the proportion and suppressive capacity of Tregs. In mouse models, SjDX5-53 protected mice against autoimmune-related colitis and psoriasis through inducing Tregs and inhibiting inflammatory T-helper (Th) 1 and Th17 responses. SjDX5-53 exhibited the promising therapeutic effects in alleviating the phenotype of immune-related colitis and psoriasis. This study displayed a screening and validation pipeline of the inducer of Tregs from helminth eggs, highlighting the discovery of new biologics inspired by co-evolution of hosts and their parasites. This study was supported by the Natural Science Foundation of China (82272368) and Natural Science Foundation of Jiangsu Province (BK20211586).

Triclocarban exposure aggravates dextran sulfate sodium-induced colitis by deteriorating the gut barrier function and microbial community in mice.

Triclocarban (TCC) is an antibacterial component widely used in personal care products with potential toxicity possessing public health issues. Unfortunately, enterotoxicity mechanisms of TCC exposure remain largely unknown. Using a combination of 16S rRNA gene sequencing, metabolomics, histopathological and biological examinations, this study systematically explored the deteriorating effects of TCC exposure on a dextran sulfate sodium (DSS)-induced colitis mouse model. We found that TCC exposure at different doses significantly aggravated colitis phenotypes including shortened colon length and altered colonic histopathology. Mechanically, TCC exposure further disrupted intestinal barrier function, manifested by significant downregulation of the number of goblet cells, mucus layer thickness and expression of junction proteins (MUC-2, ZO-1, E-cadherin and Occludin). The gut microbiota composition and its metabolites such as short-chain fatty acids (SCFAs) and tryptophan metabolites were also markedly altered in DSS-induced colitis mice. Consequently, TCC exposure markedly exacerbated colonic inflammatory status of DSS-treated mice by activating NF-κB pathway. These findings provided new evidence that TCC could be an environmental hazards for development of IBD or even colon cancer.

CRP in Outpatients with Inflammatory Bowel Disease Is Linked to the Blood Microbiota.

The circulation is a closed system that has been assumed to be free from bacteria, but evidence for the existence of a low-density blood microbiota is accumulating. The present study aimed to map the blood microbiota of outpatients with Crohn's disease (CD) or with ulcerative colitis (UC) by 16S metagenomics. A diverse microbiota was observed in the blood samples. Regardless of the type of disease, the alpha diversity of the microbiota was positively associated with C-reactive protein (CRP). The blood microbiota had a surprisingly high proportion of Proteobacteria in comparison with human oral and colonic microbiotas. There was no clear difference in the overall pattern of the microbiota between CD and UC. A non-template control (NTC) was included in the whole process to control for the potential contamination from the environment and reagents. Certain bacterial taxa were concomitantly detected in both blood samples and NTC. However, Acinetobacter, Lactobacillus, Thermicanus and Paracoccus were found in blood from both CD and UC patients but not in NTC, indicating the existence of a specific blood-borne microbiota in the patients. Achromobacter dominated in all blood samples, but a minor amount was also found in NTC. Micrococcaceae was significantly enriched in CD, but it was also detected in high abundance in NTC. Whether the composition of the blood microbiota could be a marker of a particular phenotype in inflammatory bowel disease (IBD) or whether the blood microbiota could be used for diagnostic or therapeutic purposes deserves further attention.

The Effect of Sex-Specific Differences on IL-10-/- Mouse Colitis Phenotype and Microbiota.

Sexual dimorphism is an important factor in understanding various diseases, including inflammatory bowel disease (IBD). While females typically exhibit stronger immune responses, the role of sex in IBD remains unclear. This study aimed to explore the sex-dependent differences and inflammatory susceptibility in the most extensively used IBD mouse model as they developed colitis. We monitored IL10-deficient mice (IL-10-/-) up to 17 weeks of age and characterized their colonic and fecal inflammatory phenotype, as well as their microbiota changes. Here, we originally identified IL-10-/- female mice as more prone to developing intestinal inflammation, with an increase in fecal miR-21, and dysbiosis with more detrimental characteristics compared to males. Our findings provide valuable insights into the sex-based differences in the pathophysiology of colitis and emphasize the importance of considering sex in experimental designs. Moreover, this study paves the way for future investigations aiming at addressing sex-related differences for the development of adequate disease models and therapeutic strategies, ideally enabling personalized medicine.

Mutant LRRK2 exacerbates immune response and neurodegeneration in a chronic model of experimental colitis

The link between the gut and the brain in Parkinson’s disease (PD) pathogenesis is currently a subject of intense research. Indeed, gastrointestinal dysfunction is known as an early symptom in PD and inflammatory bowel disease (IBD) has recently been recognised as a risk factor for PD. The leucine-rich repeat kinase 2 (LRRK2) is a PD- and IBD-related protein with highest expression in immune cells. In this study, we provide evidence for a central role of LRRK2 in gut inflammation and PD. The presence of the gain-of-function G2019S mutation significantly increases the disease phenotype and inflammatory response in a mouse model of experimental colitis based on chronic dextran sulphate sodium (DSS) administration. Bone marrow transplantation of wild-type cells into G2019S knock-in mice fully rescued this exacerbated response, proving the key role of mutant LRRK2 in immune cells in this experimental colitis model. Furthermore, partial pharmacological inhibition of LRRK2 kinase activity also reduced the colitis phenotype and inflammation. Moreover, chronic experimental colitis also induced neuroinflammation and infiltration of peripheral immune cells into the brain of G2019S knock-in mice. Finally, combination of experimental colitis with overexpression of α-synuclein in the substantia nigra aggravated motor deficits and dopaminergic neurodegeneration in G2019S knock-in mice. Taken together, our results link LRRK2 with the immune response in colitis and provide evidence that gut inflammation can impact brain homeostasis and contribute to neurodegeneration in PD.

A prospective study of inflammatory bowel disease phenotypes in extremes of age and comparison with adults.

Pediatric and elderly inflammatory bowel disease (IBD) are less explored, often in retrospective studies. The pediatric group has a more extensive and aggressive disease phenotype requiring aggressive treatments, whereas the elderly group may have less aggressive diseases. We prospectively compared disease characteristics of a single center cohort of IBD patients (pediatric age ≤ 16years; adults 17 to 59years; and elderly ≥ 60years) seen between September 2018 and November 2019 with at least sixmonths of follow-up. Total 266IBD patients (137 males) included 47 pediatric, 175 adults and 44 elderly patients. Among ulcerative colitis (UC) patients, pancolitis was more common in the pediatric group (p = 0.018), while the elderly group had more indolent behaviors and infrequent extraintestinal manifestations (p = 0.005). Among patients with Crohn's disease (CD), the pediatric group had more often colonic diseases (p = 0.02) and the elderly, ileal diseases (p = 0.04). The disease behavior was similar in the three age groups. Perianal disease was least common in elderly CD patients (p = 0.03). There was no treatment difference among different age groups in UC. In CD, pediatric patients needed biologics more frequently (p = 0.005), while elderly CD patients less frequently required steroids, biologics, immunosuppressants and surgery (p < 0.05). We noted differences compared to western literature such as colonic location in pediatric CD and ileal location in elderly CD. Perianal disease was less frequent in the elderlyCD group. There was no difference in treatment in the three age groups in UC, while there were no inter-age-group disease behavioral differences for UC and CD.

Extraintestinal manifestations in infl ammatory bowel diseases in children, a modern view of the problem

Inflammatory bowel disease (IBD) is a group of severe systemic diseases with a multiple intestinal and extraintestinal manifestations (EIM). EIM can affect any organ systems, determine the course, therapy and prognosis of the underlying disease. The frequency of EIM (6–80%) differs significantly in studies depending on the cohort of patients (number, age of patients, IBD phenotype). In 6–10% of children EIM are the first symptoms of the disease. The classification of EIM most often depends on the activity of the disease in the intestine. The most commonly affected «target organs» in children and adults are joints, skin and mucous membranes, eyes, and the hepatobiliary system. Physical development delay is specific for children IBD, not always reversible. The article highlights the incidence of ulcerative colitis and Crohn’s disease EIM in children and adults, analyzes the basics of epidemiology, pathogenesis, clinical manifestations, approaches to the diagnosis and treatment of arthritis, growth disorders, mucocutaneous, ocular and hepatobiliary EIM of IBD in children. Therapy of EIM associated with IBD activity is aimed at controlling the underlying disease and includes a wide range of drugs, ФНОα antagonists are the most effective. The treatment protocols for other EIM are not standardized in either adult or pediatric practice and are significantly less successful.

Exit strategies in inflammatory bowel disease: Looking beyond anti-tumor necrosis factors.

The long-term management of patients with inflammatory bowel disease (IBD) is still a matter of debate, and no clear guidelines have been issued. In clinical practice, gastroenterologists often have to deal with patients in prolonged remission after immunomodulatory or immunosuppressive therapies. When planning an exit strategy for drug withdrawal, the risk of disease relapse must be balanced against the risk of drug-related adverse events and healthcare costs. Furthermore, there is still a dearth of data on the withdrawal of novel biologics, such as the anti-α4β7 integrin antibody (vedolizumab) and anti-IL12/23 antibody (ustekinumab), as well as the small molecule tofacitinib. Models for estimating the risk of disease relapse and the efficacy of retreatment should be evaluated according to the patient's age and IBD phenotype. These models should guide clinicians in programming a temporary drug withdrawal after discussing realistic outcomes with the patient. This would shift the paradigm from an exit strategy to a holiday strategy.

Significant Racial and Ethnic Disparities Exist in Health Care Utilization in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

The incidence of inflammatory bowel disease (IBD) is rising worldwide, though the differences in health care utilization among different races and ethnicities remains uncertain. We aimed to better define this through a systematic review and meta-analysis. We explored the impact of race or ethnicity on the likelihood of needing an IBD-related surgery, hospitalization, and emergency department visit. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated with I2 values reporting heterogeneity. Differences in IBD phenotype and treatment between racial and ethnic groups of IBD were reported. Fifty-eight studies were included. Compared with White patients, Black patients were less likely to undergo a Crohn's disease (CD; OR, 0.69; 95% CI, 0.50-0.95; I2 = 68.0%) or ulcerative colitis (OR, 0.58; 95% CI, 0.40-0.83; I2 = 85.0%) surgery, more likely to have an IBD-hospitalization (OR, 1.54; 95% CI, 1.06-2.24; I2 = 77.0%), and more likely to visit the emergency department (OR, 1.74; 95% CI, 1.32-2.30; I2 = 0%). There were no significant differences in disease behavior or biologic exposure between Black and White patients. Hispanic patients were less likely to undergo a CD surgery (OR, 0.57; 95% CI, 0.48-0.68; I2 = 0%) but more likely to be hospitalized (OR, 1.38; 95% CI, 1.01-1.88; I2 = 37.0%) compared with White patients. There were no differences in health care utilization between White and Asian or South Asian patients with IBD. There remain significant differences in health care utilization among races and ethnicities in IBD. Future research is required to determine factors behind these differences to achieve equitable care for persons living with IBD.

Targeting FTO by Dac51 contributes to attenuating DSS-induced colitis

BackgroundsDextran Sulphate Sodium (DSS)-induced colitis in mice is used to mimic human Ulcerative colitis (UC) and has been used to explore the pathogenesis of UC and also to evaluate the effectiveness of the therapeutic agent. Various epigenetic pathways have been shown to play important regulatory roles in UC. Reversible N6-methyladenosine (m6A) methylation represented a new layer of post-transcriptional gene regulation that affected a variety of biological processes. Since UC patients may present the up-regulation of FTO-mediated-the reduced total m6A level, our aim was to determine the effects of Dac51, which is an inhibitor of FTO, in DSS induced colitis in mice. MethodsAcute colitis was induced by 3 % DSS in drinking water for 7 days and Dac51 treatment was administered to intraperitoneal injection from days 4–10. Clinical symptoms were analyzed, and biological samples were further collected for histological analysis and the analysis of m6A, respectively. ResultsDac51 treatment attenuated the colitis of DSS treated mice, characterized by the reduced colon shorting and histological damage. The colitis development was due to the reduced m6A level since the increased FTO expression resulted in the colitis phenotype. Dac51 treatment notably attenuated the colitis development. The inhibition of FTO activity in mice by Dac51 treatment was further confirmed by qPCR and western blotting analysis of colon tissues. ConclusionsThese results indicated that Dac51 improved DSS-induced colitis through suppression of FTO expression and provided a preclinical testing of therapeutic agents for inflammatory bowel disease.

Gut virome-colonising Orthohepadnavirus genus is associated with ulcerative colitis pathogenesis and induces intestinal inflammation in vivo

ObjectivesUlcerative colitis (UC) is a chronic inflammatory disorder of unknown aetiology. Gut virome dysbiosis is fundamental in UC progression, although its role in the early phases of the disease is...