The small intestine is essential for digestion, nutrient absorption, immune regulation, and microbial balance. Its epithelial lining, containing specialized cells like Paneth cells and tuft cells, is crucial for maintaining intestinal homeostasis. Paneth cells produce antimicrobial peptides and growth factors that support microbial regulation and intestinal stem cells, while tuft cells act as chemosensors, detecting environmental changes and modulating immune responses. Along with immune cells such as intraepithelial lymphocytes, innate lymphoid cells, T cells, and macrophages, they form a strong defense system that protects the epithelial barrier. Disruptions in this balance contribute to chronic inflammation, microbial dysbiosis, and compromised barrier function-key features of inflammatory bowel disease, celiac disease, and metabolic syndromes. Furthermore, dysfunctions in the small intestine and immune cells are linked to systemic diseases like obesity, diabetes, and autoimmune disorders. Recent research highlights promising therapeutic strategies, including modulation of epithelial and immune cell functions, probiotics, and gene editing to restore gut health and address systemic effects. This review emphasizes the pivotal roles of small intestinal epithelia and immune cells in maintaining intestinal homeostasis, their involvement in disease development, and emerging treatments for intestinal and systemic disorders.
Humans ; Intestinal Mucosa/cytology* ; Intestine, Small/cytology* ; Animals ; Inflammatory Bowel Diseases/immunology* ; Celiac Disease/immunology* ; Paneth Cells/immunology*

Objective To analyze the short-term clinical efficacy and influencing factors of ustekinumab monoclonal antibody(UST)in the treatment of Crohn′s disease(CD).Methods Retrospective cohort study was used to collect the clinical data of CD patients treated with UST in the 10th People′s Hospital affiliated to Tongji University from December 2020 to October 2022.The main analysis is the short-term clinical efficacy and influencing factors of UST treatment for CD at weeks 8 and 16,And analyze the endoscopic response rate of some patients.Results A total of 91 CD patients who first used UST were included.The 8-week clinical response rate of UST treat-ment for CD was 61.5%,and the clinical response rate was 45%;The clinical response rate at 16 weeks was 71.4%,and the clinical response rate was 54.9%.56 cases underwent endoscopic re-examination in our hospital,and the endoscopic response rate at 16 weeks was 41.1%.Univariate analysis showed that fistula(including anal fistula,personal history of anal fistula,and intestinal skin fistula)is associated with clinical remission in Crohn′s disease patients at 8/16 weeks.Further multivariate COX regression analysis showed that the presence of a history of anal fistula surgery was an independent protective factor affecting clinical remission in CD patients treated with UST at 8 weeks(HR = 0.04,95%CI:0.00～0.38;P = 0.005)and 16 weeks(HR = 0.04,95%CI:0.01～0.34;P = 0.003)compared to those without fistula;Narrow lesions are an independent risk factor for 16 week clinical remission in CD patients compared to non-narrow and non-penetrating lesions(HR = 1.75,95%CI:1.08～2.84;P = 0.023).No patients were found to have stopped medication due to serious adverse reactions.Conclusions UST can improve the clinical remission and response of CD patients at 8/16 weeks,and has good short-term clinical efficacy.CD patients with a personal history of anal fistula are recommended to use UST monoclonal antibodies,while patients with stenotic lesions should be cautious in using UST monoclonal antibodies.Whether the patient has undergone surgical treatment in the past,as well as whether UST has been used on the first or non-first line,has no significant impact on clinical remission.

Background::Histological healing is closely associated with improved long-term clinical outcomes and lowered relapses in patients with ulcerative colitis (UC). Here, we developed a novel diagnostic criterion for assessing histological healing in UC patients.Methods::We conducted a retrospective cohort study in UC patients, whose treatment was iteratively optimized to achieve mucosal healing at Shanghai Tenth People’s Hospital of Tongji University from January 2017 to May 2022. We identified an inflammatory cell enumeration index (ICEI) for assessing histological healing based on the proportions of eosinophils, CD177 + neutrophils, and CD40L + T cells in the colonic lamina propria under high power field (HPF), and the outcomes (risks of symptomatic relapses) of achieving histological remission vs. persistent histological inflammation using Kaplan-Meier curves. Intrareader reliability and inter-reader reliability were evaluated by each reader. The relationships to the changes in the Nancy index and the Geboes score were also assessed for responsiveness. The ICEI was further validated in a new cohort of UC patients from other nine university hospitals. Results::We developed an ICEI for clinical diagnosis of histological healing, i.e., Y = 1.701X 1 + 0.758X 2 + 1.347X 3 - 7.745 (X 1, X 2, and X 3 represent the proportions of CD177 + neutrophils, eosinophils, and CD40L + T cells, respectively, in the colonic lamina propria under HPF). The receiver operating characteristics curve (ROC) analysis revealed that Y <-0.391 was the cutoff value for the diagnosis of histological healing and that an area under the curve (AUC) was 0.942 (95% confidence interval [CI]: 0.905-0.979) with a sensitivity of 92.5% and a specificity of 83.6% ( P <0.001). The intraclass correlation coefficient (ICC) for the intrareader reliability was 0.855 (95% CI: 0.781-0.909), and ICEI had good inter-reader reliability of 0.832 (95% CI: 0.748-0.894). During an 18-month follow-up, patients with histological healing had a substantially better outcome compared with those with unachieved histological healing ( P <0.001) using ICEI. During a 12-month follow-up from other nine hospitals, patients with histological healing also had a lower risk of relapse than patients with unachieved histological healing. Conclusions::ICEI can be used to predict histological healing and identify patients with a risk of relapse 12 months and 18 months after clinical therapy. Therefore, ICEI provides a promising, simplified approach to monitor histological healing and to predict the prognosis of UC.Registration::Chinese Clinical Trial Registry, No. ChiCTR2300077792.

Objective:To evaluate the efficacy and safety of adalimumab (ADA) in the treatment of Crohn′s disease (CD), and to analyze the predictive factors of ADA efficacy.Methods:From January 2020 to December 2020, 49 CD patients treated with ADA at the Department of Gastroenterology, Tenth People′s Hospital of Tongji University of Shanghai were enrolled. The clinical data before treatment were collected. During 12 weeks of ADA treatment, the patients were followed up every 2 weeks, the laboratory examinations were conducted every 4 weeks, and colonoscopy examination was rechecked at the 12th week. The improvement of the main symptoms of patients was assessed at 2nd, 4th, and 6th week during ADA treatment. At the 12th week after ADA treatment, the clinical response (Crohn′s disease activity index (CDAI) score decreased ≥70 points from baseline), clinical remission (CDAI score < 150 points), endoscopic response (simple endoscopic score for Crohn′s disease (SES-CD) decreased >50% from baseline) and endoscopic remission (SES-CD ≤2 points or Rutgeerts score ≤1 point), closure of anal fistula of CD patients complicated with anal fistula and occurrence of adverse reactions during treatment were recorded. The predictive factors of clinical remission of CD patients after ADA treatment for 12 weeks were analyzed. The Mann-Whitney U test and binary logistic regression analysis were used for statistical analysis. Results:The main symptom improved rates of 49 CD patients received ADA treatment at 2nd, 4th and 6th week were 75.5% (37/49), 95.9% (47/49) and 98.0% (48/49), respectively, and the main symptom improved time was 14.0 d (7.0 d, 17.0 d). After ADA treatment for 12 weeks, the clinical remission rate was 55.1% (27/49), the clinical response rate was 73.5% (36/49), the endoscopic remission rate was 43.3% (13/30), the endoscopic response rate was 55.6% (15/27), the anal fistula closure rate was 7/18, and the overall incidence of adverse reactions was 24.5% (12/49). The baseline of fecal calprotectin (FC) level of patients in the clinical remission group (27 cases) was lower than that of the patients in the active disease group (22 cases) (111.0 μg/g, 26.3 μg/g to 125.6 μg/g vs. 540.5 μg/g, 420.2 μg/g to 866.9 μg/g), and the difference was statistically significant ( Z=-4.44, P<0.001). The results of binary logistic regression analysis showed that baseline FC level was an independent predictive factor of clinical remission in CD patients treated with ADA for 12 weeks ( OR=1.08, 95%confidence interval 1.02 to 1.14, P=0.013). When the baseline FC cut-off value was 172.39 g/g, the sensitivity and specificity of it in predicting clinical remission in CD patients treated with ADA for 12 weeks were 81.48% and 90.91%, and the area under the receiver operator characteristic curve was 0.87 ( P<0.001). Conclusions:ADA is safe and effective in the treatment of CD. The baseline FC level is an independent predictive factor of clinical remission in CD patients treated with ADA for 12 weeks.

Objective:To determine a simpler and more practical scoring standard for predicting mucosal histological healing in ulcerative colitis (UC).Methods:From April 11, 2017 to February 8, 2021, 68 UC patients diagnosed with mucosal healing under endoscopy and hospitalized at Department of Gastroenterology, the Tenth People′s Hospital of Tongji University and during the same period 60 healthy individuals who underwent endoscopy for health checkup were retrospectively analyzed. Modified Mayo score and ulcerative colitis endoscopic index of severity (UCEIS), the modified Nancy index and Robarts histopathology index were determined based on the collected clinical data, endoscopic reports and histopathological evaluation. The proportions of neutrophils, eosinophils, and plasma cells in the colonic mucosal lamina propria were calculated. The proportions of activated neutrophils and T cells in the colonic mucosal lamina were calculated according to CD177 and CD40L, respectively. The new clinical and laboratory diagnostic formulas were determined by multivariate logistic regression analysis, the effectiveness of the equations was evaluated by receiver operating characteristic curve (ROC).Results:Among the 68 patients with UC, the modified Mayo score was 0.7 (0.4, 1.1), the UCEIS was 0.5 (0.3, 0.8), the Nancy index was 5.9±3.2, and the Robarts histopathology index was 2.6±1.7. According to multivariate logistic regression analysis, the formula for clinical diagnosis of histological healing was Y1=-21.09+ 355.9 X1+ 305.8 X2+ 44.91 X3 ( X1, X2 and X3 were the proportions of neutrophils, eosinophils, and plasma cells, respectively). The results of ROC analysis indicated that Y1<-0.747 was the cut-off value of diagnosis of histological healing, and the area under the curve (AUC) was 0.986 and 95% confidence interval ( CI) was 0.922 to 1.000 ( P<0.001), the sensitivity was 97.10% and the specificity was 91.20%. The formula of laboratory diagnosis of histological healing was Y2=-10.57+ 469.1 X1 + 132.7 X2 + 101.2 X3 + 18.56 X4 ( X1, X2, X3, and X4 were the proportions of CD177 + neutrophils, eosinophils, CD40L + T cells and plasma cells, respectively). The results of ROC analysis indicated that Y2<1.960 was the cut-off value of diagnosis of histological healing, and the AUC was 0.980, 95% CI was 0.913 to 0.999 ( P<0.001), the sensitivity was 84.78%, and the specificity was 100.00%. The new clinical and laboratory diagnostic criteria were positively correlated with the Nancy histological index ( r=0.411 and 0.308, P=0.001 and 0.011), and Robarts histopathology index ( r=0.311, 0.273, P=0.010 and 0.024). Conclusions:Compared with the Nancy index, the new clinical and laboratory diagnostic criteria are simpler and more practical. The new clinical diagnostic formula Y1<-0.747 and the new laboratory diagnosis formula Y2<1.960 are the independent factors for predicting histological healing in UC patients.

Immunomodulators and biological agents are widely used in inflammatory bowel disease (IBD), and induce remission effectively. However, these drugs are related to serious adverse events, and coupled with increasing treatment costs. Therefore, once patients with IBD are in remission, the safety and feasibility of drug de-escalation should be considered, and the risk of continuing medical therapy against the risk of disease relapse must be weighed. This review article analyzed the published literatures on de-escalation of immunomodulators and biological agents in patients with Crohn's disease and ulcerative colitis, identifying the risk factors of relapse after drug withdrawal, such as disease activity, prognostic features and previous disease course, and discussed the strategies for de-escalation and use of proactive therapeutic drug monitoring, so as to provide some guidance for clinical practice.

Objective:To investigate the clinical characteristics and change trend of patients with perianal lesions before or after Crohn′s disease (CD) diagnosed.Methods:From January 2008 to September 2018, at The Tenth People′s Hospital Affiliated to Tongji University, the clinical data of 747 hospitalized CD patients were retrospectively collected, 293 patients were PCD patients. The clinical characteristics of PCD patients before or after CD diagnosed were analyzed and the change trend was followed. T test, Mann-Whitney U test, and Chi-square test were performed for statistical analysis. Multivariate logistic regression analysis was used to analyze factors associated with perianal lesions onset time. Spearman correlation analysis was used to analyze the change trend of clinical characteristics. Results:Before CD diagnosis, 86.3% (253/293) PCD patients had perianal lesions. The median follow-up time (range) was 72 months (36 to 108 months). Compared with the patients presented with perianal lesions after CD diagnosis, the onset age of patients with perianal lesions before CD diagnosis was younger ((36.0±12.6) years vs. (24.2±10.2) years), and the rates of male (62.5%, 25/40 vs. 77.9%, 197/253), non-structuring and non-penetrating type (32.5%, 13/40 vs. 56.9%, 144/253) and perianal surgery (55.0%, 22/40 vs.76.7%, 194/253) were high, but low rate of abdominal surgery (37.5%, 15/40 vs. 13.0%, 33/253), and the differences were statistically significant ( t=2.630, χ2=4.442, 8.379, 8.379 and 15.081; all P<0.05). The results of logistic multivariate analysis showed that before CD diagnosis, non-structuring and non-penetrating type was more common than structuring type (odds ratio ( OR)=0.447, 95% confidence interval ( CI) 0.207 to 0.962, P=0.039) and penetrating type ( OR=0.264, 95% CI 0.089 to 0.780, P=0.016). The short disease duration of CD ( OR=0.981, 95% CI 0.968 to 0.995, P=0.008), structuring type ( OR=2.239, 95% CI 1.040 to 4.822, P=0.039) and penetrating type ( OR=3.788, 95% CI 1.281 to 11.198, P=0.016) were the risk factors of perianal lesions after CD diagnosed. The number of PCD patients ( r=0.964, P<0.01) and the proportion of biological agents ( r=0.879, P<0.01) increased with years, while PCD duration ( r=-0.828, P<0.01) and the rate of abdominal surgery significantly decreased with years ( r=-0.882, P<0.01). The proportion of biological agents was negatively correlated with the rate of abdominal surgery ( r=-0.770, P=0.006). Conclusions:The perianal lesions should be closely monitored in adult CD patients with short disease duration, structuring type and penetrating type for early diagnosis and treatment. Biological agents can improve the clinical outcomes of PCD.

Objective:To explore the role of infliximab (IFX) in the repairation of intestinal mucosal barrier in Crohn′s disease (CD).Methods:From January 2018 to October 2019, in Shanghai Tenth People′s Hospital, 382 CD patients were selected. All the patients were treated with IFX. And 103 individuals who underwent colonoscopy were selected as healthy control group. The general clinical data, fasting blood samples and intestinal mucosa tissue samples of CD patients and healthy controls were collected. The body mass index (BMI), hemoglobin, albumin, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and relative inflammation factors, including tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-1, IL-2, IL-6, IL-8, IL-10 and IL-17A, and their mRNA expression levels were detected. Crohn′s disease activity index (CDAI) and simplified endoscopic score for Crohn′s disease (SES-CD) were used to evaluate the disease activity of CD patients. The expression levels of occudin, claudin-1, zonula occluden-1 (ZO-1) and junctional adhesion molecule-A (JAM-A) were measured by Western blotting. The intestinal mucosal epithelial cells were observed by transmission electron microscope. T test was used for statistical analysis. Results:Before treatment, BMI, and hemoglobin and albumin levels of CD patients were all lower than those of healthy control group ((18.3±1.8) kg/m 2 vs. (20.2±1.2) kg/m 2, (95.3±8.4) g/L vs. (129.2±5.7) g/L, (33.2±5.4) g/L vs. (50.3±3.2) g/L), and the differences were statistically significant ( t=3.457, 5.342 and 2.674, all P<0.05). After treatment the BMI and hemoglobin levels of CD patients were higher than those before treatment ((19.5±2.1) kg/m 2 vs. (18.3±1.8) kg/m 2, (117.2±10.3) g/L vs. (95.3±8.4) g/L), and the CRP level, CDAI score and SES-CD score were lower than those before treatment ((16.3±2.3) mg/L vs. (47.2±9.3) mg/L, 113.2±12.5 vs. 245.2±23.5, 5.0±2.1 vs. 10.0±4.3), and the differences were statistically significant ( t=2.090, 2.339, 2.432, 6.345 and 5.234, all P<0.05). The expression levels of TNF-α, IFN-γ, IL-2, IL-6, IL-8, IL-17A and their mRNA levels of healthy control group were lower than those of CD patients before treatment ((1.1±0.4) ng/L vs.(158.2±38.3) ng/L, (3.2±0.8) ng/L vs. (28.3±13.4) ng/L, (2.7±1.3) ng/L vs. (3.3±2.4) ng/L, (5.2±0.3) ng/L vs. (16.3±7.4) ng/L, (16.3±6.3) ng/L vs. (18.9±10.2) ng/L, (10.5±2.3) ng/L vs. (38.5±11.2) ng/L; 1.00±0.00 vs. 4.68±0.34, 7.83±0.32, 1.25±0.46, 8.36±0.44, 2.01±0.89 and 6.83±0.53, respectively), and the differences were statistically significant ( t=2.345, 6.456, 3.008, 4.009, 7.045, 10.223, 8.345, 11.235, 1.114, 12.334, 5.304 and 5.678, all P<0.05). After treatment the TNF-α, IFN-γ, IL-2, IL-6, IL-8, IL-17A expression levels and their mRNA levels of CD patients were lower than those before treatment ((106.4±29.9) ng/L vs. (158.2±38.3) ng/L, (25.7±10.8) ng/L vs. (28.3±13.4) ng/L, (2.9±1.7) ng/L vs. (3.3±2.4) ng/L, (15.4±4.2) ng/L vs. (16.3±7.4) ng/L, (17.2±8.7) ng/L vs. (18.9±10.2) ng/L, (29.9±12.7) ng/L vs. (38.5±11.2) ng/L, 2.45±0.21 vs. 4.68±0.34, 3.75±0.18 vs. 7.83±0.32, 1.09±0.22 vs. 1.25±0.46, 3.78±0.21 vs. 8.36±0.44, 1.67±0.33 vs. 2.01±0.89, 2.96±0.11 vs. 6.83±0.53), and the differences were statistically significant ( t=9.345, 2.456, 2.334, 2.090, 3.009, 8.345, 4.567, 6.445, 2.046, 7.774, 3.008 and 8.867, all P<0.05). The results of Western blotting showed that the expression levels of occudin, claudin-1, ZO-1 and JAM-A in the intestinal mucosa of CD patients before treatment were lower than those of the healthy control group (0.21±0.03 vs. 1.00±0.02, 0.17±0.07 vs. 1.00±0.01, 0.16±0.06 vs. 1.00±0.04, 0.26±0.08 vs. 1.03±0.04). After treatment the expression levels of occudin, claudin-1, ZO-1 and JAM- A mRNA in the intestinal mucosa of CD patients were higher than those before treatment (0.77±0.08 vs. 0.21±0.03, 0.69±0.08 vs. 0.17±0.07, 0.78±0.09 vs. 0.16 ±0.06, 0.72±0.07 vs. 0.26±0.08), and the differences were statistically significant ( t=4.567, 6.346, 5.557, 8.456, 9.678, 8.671, 10.456 and 7.456, all P<0.05). Conclusions:IFX can effectively relieve the disease activity and improve the nutritional status of CD patients. IFX maintains the expression of intestinal epithelial tight junction protein by reducing inflammatory response, and repairs the intestinal mucosal barrier of CD patients.

Objective:To screen the risk factors of psychology problems and quality of life of patients with inflammatory bowel disease (IBD) by questionnaire, and to explore the impact of anxiety and depression on the quality of life and disease of IBD patients, in order to guide the treatment of IBD.Methods:From June 15 to July 15 in 2019, 171 IBD patients diagnosed in the Department of Gastroenterology, the Tenth People′s Hospital of Tongji University in Shanghai were investigated by internet questionnaire. Finally 136 IBD patients (IBD group) were enrolled. During the same period 121 healthy individuals with no difference in age and gender were selected as healthy control group. IBD clinical questionnaire, the generalized anxiety disorder (GAD)-7, patient health questionnare (PHQ)-9 depression screening and the short form 36-item health survey (SF-36) quality of life evaluation scale were used in IBD group. General situation questionnaire, GAD-7, PHQ-9 and SF-36 scale were conducted in healthy control group. Chi-square test, Binary logistic regression analysis, Ordinal logistic regression analysis, and Pearson correlation analysis were used for statistical analysis.Results:In IBD group, 87(64.0%) were males and 49(36.0%) were females; 25 cases (18.4%) were ulcerative colitis (UC) and 111 cases (81.6%) were Crohn′s disease (CD); and the median age was (32(26, 40)) years old. In healthy control group, 68 (56.2%) were males and 53(43.8%) were females; the median age was (32(26, 37)) years old. The incidence of anxiety in UC patients and CD patients was 64.0%(16/25) and 64.9%(72/111), respectively, and the incidence of depression in UC and CD was 72.0%(18/25) and 58.6%(65/111), respectively. There were no significant differences in the incidence of anxiety and depression between UC patients and CD patients (both P>0.05). Role-emotional (odds ratio ( OR)=0.965, 95% confidence interval ( CI) 0.937 to 0.994, P=0.017) and mental health ( OR=0.940, 95% CI 0.896 to 0.985, P=0.010) may be the independent factors of depression. Physiological function ( OR=1.040, 95% CI 1.010 to 2.730, P=0.022) was the independent factors of depression. There was no significant correlation between the duration of disease and the quality of life ( P>0.05). There was no significant correlation between disease activity and quality of life, however it was related to physiological function ( r=0.15, P=0.046). The physiological function of IBD patients in remission stage was better than that of patients in activity stage. Depression was negatively correlated with quality of life ( r=-0.55, P<0.01), and with a linear relationship ( r=19.429, intercept was 744.455, P<0.01). Anxiety was not correlated with quality of life ( P>0.05). Depression was negatively correlated with changes of physical function, role-physical function, physical pain, general health, vitality, social function, emotional function, mental health, and reported health transition ( r=-0.234, -0.358, -0.454, -0.449, -0.566, -0.485, -0.441, -0.597, and -0.193, all P<0.05). Conclusions:IBD patients are prone to anxiety and depression. Depression is negative correlated with quality of life. It is very important to screen and intervene mental disorders in IBD patients, especially in patients with depression. Controlling the activity of IBD and relieving the clinical symptoms of patients may be effective in improving anxiety and depression. The treatment of IBD itself is the basis of IBD psychotherapy.