Long-term changes in the gut microbiota after triple therapy, sequential therapy, bismuth quadruple therapy and concomitant therapy for Helicobacter pylori eradication in Chinese children.

BACKGROUND: We previously reported that the administration of 14-day standard triple therapy (TT), sequential therapy (ST), bismuth-based quadruple therapy (BT), and concomitant therapy (CT) as the first-line therapy for Helicobacter pylori infection in Chinese children achieved eradication rates of 74.1%, 69.5%, 89.8%, and 84.6%, respectively. In this follow-up study, we further evaluated the short- and long-term effects of the four regimens on the gut microbiota in these children. METHODS: We prospectively recruited treatment-naïve children with H. pylori infection. Fecal samples were collected at week 0, 2, 6, and 52, and alterations in the gut microbiota were analyzed by 16S rRNA gene sequencing. RESULTS: Sixty-three patients participated in this study (16 with TT, 15 with ST, 16 with BT and 16 with CT). At week 2, the alpha diversity (Shannon and Chao 1 index) was significantly reduced in the TT (p = 0.008, p < 0.001), ST (p < 0.001, p < 0.001), BT (p < 0.001, p < 0.001) and CT groups (p < 0.001, p < 0.001). Some changes persisted in the ST, BT, and CT groups at week 6, and all were restored (expect p = 0.02 with Chao 1 index in the CT group) at week 52. The beta diversity was significantly changed in the BT (p = 0.001) and CT groups (p = 0.001) 2 weeks post-eradication and restored 1 year after therapy. Immediately after therapy, the relative abundance of Proteobacteria was strikingly increased in the ST (p = 0.005), BT (p < 0.001) and CT groups (p < 0.001), and the genus-level analysis showed that the abundances of 23.1%, 43.3%, 78.6%, and 78% of the bacterial genera in the TT, ST, BT, and CT groups were significantly changed. All these changes returned to almost the pre-eradication level 1 year post-eradication. CONCLUSION: Eradication of H. pylori infection can lead to transient dysbiosis of gut microbiota, and these changes almost recovered 1 year post-eradication, which indicates the long-term safety of H. pylori therapy.

Mast Cell Tryptase Contributes to Pancreatic Cancer Growth through Promoting Angiogenesis via Activation of Angiopoietin-1.

Pancreatic cancer is a highly lethal malignancy and one of the leading causes of cancer-related death. During the development and progression of cancer, tumor angiogenesis plays a crucial role. A great deal of evidence has revealed that human mast cells (MCs) contributed to tumor angiogenesis through releasing several pro-angiogenetic factors, among which tryptase is one of the most active. However, the role of mast cell tryptase (MCT) in human pancreatic cancer angiogenesis is still not well documented. In this study, we examined the MCT levels in serum from pancreatic cancer patients and evaluated the correlationship of the MCT level and tumor angiogenesis. In addition, the effect of MCT on endothelial cell proliferation and tube formation was investigated both in vitro and in nude mice bearing pancreatic tumor. It was found that MCT contributes to endothelial cell growth and tube formation via up-regulation of angiopoietin-1 expression. Moreover, using the MCT inhibitor nafamostat, tryptase-induced angiogenesis was obviously suppressed both in vitro and in vivo. Our findings suggest that MCT plays an important role in pancreatic cancer angiogenesis and tumor growth via activating the angiopoietin-1 pathway, and tryptase inhibitors may be evaluated as an effective anti-angiogenetic approach in pancreatic cancer therapy.

The Protective Effects of Exclusive Enteral Nutrition Formulas on Growth Factor Expression and the Proximal Tibial Epiphyseal Growth Plate in a TNBS-Induced IBD Rat Model.

OBJECTIVE: This study aimed to evaluate the effectiveness of different types of nutritional formulas in a rat model of TNBS-induced IBD. METHODS: IBD was induced with TNBS in 4-week-old rats that were then fed different exclusive enteral nutrition diets for 7 days. The length of the tibia and the number of chondrocytes in the proximal tibias were analyzed at 7 days after supplementation. Immunohistochemical analysis, ELISA and real-time PCR were performed to evaluate the levels of growth hormone receptor (GHR) and insulin-like growth factor-I receptor (IGF-IR), the growth factors IGF-I and insulin-like growth factor-binding protein-3 (IGFBP3) , bone morphogenetic protein (BMP)-2 and BMP-6 respectively. RESULTS: The results demonstrated that the tibia length of the peptide formula group was longer than that of the IBD-Modulen(®) formula and normal diet groups (P < 0.05). Furthermore, the number of chondrocytes of the proximal tibial was more pronounced in the peptide formula group compared to the other groups (P < 0.05). The peptide formula was also more effective in increasing the expression of GHR compared to the other groups (P < 0.05), while the expression of IGF-IR was not significantly different (P > 0.05). In addition, the IGF-I and IGFBP3 levels were more pronounced in the peptide formula supplement group (P < 0.05), and the expression of BMP-2 and BMP-6 mRNA in the proximal tibia growth plate from the peptide formula group was higher than that in the ordinary formula and normal diet groups (P < 0.05). CONCLUSIONS: EEN, and particularly a peptide formula, exerted protective effects on the proximal tibial epiphyseal growth plate in a TNBS-induced IBD model.

Text Messages to Promote Physical Activity in Patients With Cardiovascular Disease: A Micro-Randomized Trial of a Just-In-Time Adaptive Intervention.

BACKGROUND: Text messages may enhance physical activity levels in patients with cardiovascular disease, including those enrolled in cardiac rehabilitation. However, the independent and long-term effects of text messages remain uncertain. METHODS: The VALENTINE study (Virtual Application-supported Environment to Increase Exercise) was a micro-randomized trial that delivered text messages through a smartwatch (Apple Watch or Fitbit Versa) to participants initiating cardiac rehabilitation. Participants were randomized 4× per day over 6-months to receive no text message or a message encouraging low-level physical activity. Text messages were tailored on contextual factors (eg, weather). Our primary outcome was step count 60 minutes following a text message, and we used a centered and weighted least squares mean method to estimate causal effects. Given potential measurement differences between devices determined a priori, data were assessed separately for Apple Watch and Fitbit Versa users over 3 time periods corresponding to the initiation (0-30 days), maintenance (31-120 days), and completion (121-182 days) of cardiac rehabilitation. RESULTS: One hundred eight participants were included with 70 552 randomizations over 6 months; mean age was 59.5 (SD, 10.7) years with 36 (32.4%) female and 68 (63.0%) Apple Watch participants. For Apple Watch participants, text messages led to a trend in increased step count by 10% in the 60-minutes following a message during days 1 to 30 (95% CI, -1% to +20%), with no effect from days 31 to 120 (+1% [95% CI, -4% to +5%]), and a significant 6% increase during days 121 to 182 (95% CI, +0% to +11%). For Fitbit users, text messages significantly increased step count by 17% (95% CI, +7% to +28%) in the 60-minutes following a message in the first 30 days of the study with no effect subsequently. CONCLUSIONS: In patients undergoing cardiac rehabilitation, contextually tailored text messages may increase physical activity, but this effect varies over time and by device. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04587882.

ASSESSING TIME-VARYING CAUSAL EFFECT MODERATION IN THE PRESENCE OF CLUSTER-LEVEL TREATMENT EFFECT HETEROGENEITY AND INTERFERENCE.

The micro-randomized trial (MRT) is a sequential randomized experimental design to empirically evaluate the effectiveness of mobile health (mHealth) intervention components that may be delivered at hundreds or thousands of decision points. MRTs have motivated a new class of causal estimands, termed "causal excursion effects", for which semiparametric inference can be conducted via a weighted, centered least squares criterion (Boruvka et al., 2018). Existing methods assume between-subject independence and non-interference. Deviations from these assumptions often occur. In this paper, causal excursion effects are revisited under potential cluster-level treatment effect heterogeneity and interference, where the treatment effect of interest may depend on cluster-level moderators. Utility of the proposed methods is shown by analyzing data from a multi-institution cohort of first year medical residents in the United States.

A randomized trial of a mobile health intervention to augment cardiac rehabilitation.

Mobile health (mHealth) interventions may enhance positive health behaviors, but randomized trials evaluating their efficacy are uncommon. Our goal was to determine if a mHealth intervention augmented and extended benefits of center-based cardiac rehabilitation (CR) for physical activity levels at 6-months. We delivered a randomized clinical trial to low and moderate risk patients with a compatible smartphone enrolled in CR at two health systems. All participants received a compatible smartwatch and usual CR care. Intervention participants received a mHealth intervention that included a just-in-time-adaptive intervention (JITAI) as text messages. The primary outcome was change in remote 6-minute walk distance at 6-months stratified by device type. Here we report the results for 220 participants enrolled in the study (mean [SD]: age 59.6 [10.6] years; 67 [30.5%] women). For our primary outcome at 6 months, there is no significant difference in the change in 6 min walk distance across smartwatch types (Intervention versus control: +31.1 meters Apple Watch, -7.4 meters Fitbit; p = 0.28). Secondary outcomes show no difference in mean step counts between the first and final weeks of the study, but a change in 6 min walk distance at 3 months for Fitbit users. Amongst patients enrolled in center-based CR, a mHealth intervention did not improve 6-month outcomes but suggested differences at 3 months in some users.

Recurrent abdominal pain, vomiting, velvet-like changes in the small intestine in a patient with multiple acyl-CoA dehydrogenase deficiency: a case report.

Multiple acyl-CoA dehydrogenase deficiency (MADD) is an inborn error of metabolism in fatty acid oxidation. We described an unusual case of recurrent vomiting and abdominal pain in a child with MADD, presenting with velvet-like changes in the small intestine. Because of prominent gastrointestinal manifestations and small intestine ulcers, the patient was first diagnosed as Crohn's disease. The patient was admitted to our institution because of recurrent symptoms despite treatment. Upper and lower endoscopy, computed tomography and trios exome sequencing were performed. This patient underwent a repeated video endoscopy, which showed velvet-like changes in the small intestine rather than ulcers. Liver steatosis was identified by computed tomography. Serum tandem mass spectrometry showed elevated C8 and C10. Trios exome sequencing revealed compound heterozygous variants of c.250G>A, 524G>T in ETFDH. The diagnosis of MADD was made. Patient responded to oral riboflavin treatment. With this case, we aimed to highlight the importance of tandem mass spectrometry and genetic sequencing, especially when the endoscopic findings are not pathognomonic in pediatric cases with recurrent gastrointestinal complaints. We confirmed the diagnosis with next generation sequencing, and described unusual findings of velvet-like changes mimicking ulcers in the small intestine in this patient with MADD.

Thalidomide Inhibits Angiogenesis via Downregulation of VEGF and Angiopoietin-2 in Crohn's Disease.

Immune-mediated angiogenesis is important in the pathogenesis of inflammatory bowel disease and targeted treatment could alleviate the disease. Thalidomide is an effective drug in inflammatory bowel disease, which might be related to its multiple role in anti-inflammatory, immunoregulatory, and anti-angiogenesis. This study is to investigate the effect of thalidomide on angiogenesis in tissues from patients and in vitro cells. Angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), VEGF, and CD31 expressions in intestinal mucosa from pediatric CD patients before and after thalidomide treatment were measured by immunohistochemistry. Western blotting and polymerase chain reaction were performed to characterize the change of angiogenic factors before and after treatment in remission. Human umbilical vein endothelial cells (HUVECs) treated by thalidomide were used to examine its effect on endothelial cell proliferation and migration and capillary-like structures. Results showed that VEGF and Ang-2 levels were significantly greater in CD patients over controls. Thalidomide produced a significant reduction in protein expression of Ang-2 and VEGF, along with a decrease in mRNA expression of Ang-2. While, Ang-1 level did not show a statistically significant change. Thalidomide significantly inhibited cell proliferation in a dose-dependent manner. It also suppressed VEGF- and Ang-2-induced cell migration and capillary-like tube formation in HUVECs. Therefore, our study suggests that VEGF and Ang-2 levels are up-regulated in pediatric CD patients. It also indicated that thalidomide can be able to deactivate endothelium by the downregulation effect on angiogenic factors by targeting VEGF and Ang-2.

Effect of Exclusive Enteral Nutrition on the Disease Process, Nutrition Status, and Gastrointestinal Microbiota for Chinese Children With Crohn's Disease.

BACKGROUND: The aim of this study was to prospectively study the effect of exclusive enteral nutrition (EEN) treatment on Chinese pediatric Crohn's disease (CD) patients. METHODS: Thirty-one newly diagnosed CD patients were enrolled in this study and treated with EEN for 8 weeks. Twelve healthy controls (HCs) donated their fecal samples. Statistical methods were used to compare the differences. RESULTS: According to the Simple Endoscopic Score for CD (SES-CD) at the end of the EEN treatment, 21 patients with SES-CD ≤4 were classified into the remission group (CD-RE), and 10 patients with SES-CD >4 were classified into the nonremission group (CD-NRE). After EEN therapy, there was a significant decrease in the SES-CD, the weighted Pediatric Crohn's Disease Activity Index (wPCDAI), and fecal calprotectin (FCP) in the CD-RE group (all P < .001). The wPCDAI and FCP also decreased in the CD-NRE group (both P < .05). In terms of nutrition improvement, the CD-RE group patients showed more improvement in weight gain, hemoglobin, and serum albumin level than the CD-NRE group patients (all P < .05). For the microbiota, the CD patients had a lower bacterial diversity and different bacterial community compared with HCs. EEN increased overall diversity and was able to shift the dysbiosis in CD patients toward a healthier state. Absence of improvement in wPCDAI and Shannon index at 2 weeks predicts poor response at the end of EEN. CONCLUSION: EEN can be used in most Chinese pediatric CD patients to induce remission and improve nutrition.

Potential protein-phenotype correlation in three lipopolysaccharide-responsive beige-like anchor protein-deficient patients.

BACKGROUND: Patients with lipopolysaccharide (LPS)-responsive beige-like anchor protein (LRBA) deficiency have a variety of clinical symptoms, but there is no apparent genotype-phenotype correlation, and patients carrying the same mutations may have different phenotypes. Therefore, it is not easy for doctors to make a decision regarding hematopoietic stem cell transplantation (HSCT) for LRBA-deficient patients. We hypothesized that there may be a protein-phenotype correlation to indicate HSCT for LRBA-deficient patients. AIM: To report on three Chinese LRBA-deficient patients and determine the correlation between residual protein expression and disease phenotypes. METHODS: Clinical data of three Chinese LRBA-deficient patients were collected, and protein levels were detected by Western blot analysis. In addition, LRBA mutation information of another 83 previously reported patients was summarized. RESULTS: All the major clinical findings indicated enteropathy, but patients 1 and 3 presented with more severe symptoms than patient 2. Endoscopy and histology indicated nonspecific colitis for patients 1 and 3 but Crohn's disease-like colitis for patient 2. Compound heterozygous mutations in LRBA were found in patient 1, and homozygous mutations in LRBA were found in patient 2 and patient 3. Only patient 2 responded well to traditional immunosuppressive treatment. Residual expression of the LRBA protein in patients 1 and 3 was very low, but in patient 2, a more than 0.5-fold in expression of the LRBA protein was found compared to that in the control. After HSCT, patient 1 had increased LRBA protein expression. We summarized the genetic information of 86 patients, and the mutations in patients 1 and 3 were novel mutations. CONCLUSION: We described three Chinese LRBA-deficient patients, two of whom carried novel mutations. These patients had no genotype-phenotype correlations, but their residual LRBA protein expression might be associated with disease outcome and could be an indicator for HSCT.

Fecal Microbial Signatures Are Associated With Engraftment Failure Following Umbilical Cord Blood Transplantation in Pediatric Crohn's Disease Patients With IL10RA Deficiency.

OBJECTIVES: Umbilical cord blood transplantation (UCBT) is associated with a relatively high rate of engraftment failure. This study aimed at exploring whether any fecal microbiota could be associated with engraftment failure following UCBT in Crohn's disease patients with IL10RA deficiency. METHODS: Thirteen patients were recruited and their 230 fecal samples were collected longitudinally from immediately before conditioning chemotherapy to 8 weeks post the UCBT. The V3-V4 regions of the bacterial 16S rRNA gene were amplified by PCR and sequenced, followed by bioinformatics analyses. RESULTS: Following the UCBT, 7 out of 13 patients achieved neutrophil and platelet engraftment with a median of 21 and 28 days, respectively (S group), while 6 patients failed to achieve engraftment (F group). In comparison with that in the S group, significantly lower Shannon diversity values on the UCBT day (P = 0.0176) and less abundance of Bifidobacterium longum, Bifidobacterium pseudolongum, Enterobacteriaceae_538000, and one taxon of Lachnospiraceae family was detected in the F group, accompanied by significantly higher abundances of four taxa including Lautropia, Pseudomonas, and species Microvirgula aerodenitrificans during the chemotherapy period as well as UCBT. The abundances of thirty OTUs were correlated significantly with clinical indices. CONCLUSIONS: Microbial indicators of reduced diversity of microbiota and signatures of specific bacterial abundances, such as a lower abundance of Bifidobacterium longum, for engraftment failure would require validation. These indicators may help for the risk stratification in patients with IL10RA deficiency undergoing UCBT.

Phenotypic Characterization of Very Early-Onset Inflammatory Bowel Disease with Interleukin-10 Signaling Deficiency: Based on a Large Cohort Study.

BACKGROUND: Interleukin-10 (IL10)/interleukin-10 receptor (IL10R) deficiency is a rare disease with life-threatening infantile-onset colitis. We sought to accurately phenotype this disorder based on a large cohort of patients with a proven defect of IL10 signaling and to clarify the effects of allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: We analyzed the phenotypes of our 61 patients and reviewed 78 other previously reported cases with identified mutations in the genes encoding IL10 or IL10R. We also compared the clinical features of patients with interleukin-10 receptor B (IL10RB), interleukin-10 receptor A (IL10RA), and IL10 mutations. The therapeutic effects of allogeneic HSCT were evaluated. RESULTS: We found that the disease onset time was extremely early: 70.3% within 30 days postnatal and 94.9% within the first 6 months of life. In addition, 94.2% of patients typically presented with perianal lesions. Oral ulcers and skin rash were common extra-intestinal manifestations (33.8% and 51.8%, respectively). There was no statistically significant difference in disease onset time, perianal lesion involvement, or mortality rate among patients with IL10RB, IL10RA, or IL10 deficiency. However, the surgery rate was higher in patients with IL10RB mutations than in those with IL10 or IL10RA mutations (P < 0.05). Compared with those with IL10RA deficiency, a higher percentage (32%, 9 of 28) of patients with IL10RB mutations developed B-cell lymphoma (P < 0.01). Compared with other regions, a higher percentage (98.7%) of IL10RA mutations was detected among patients in East Asia countries (P < 0.01), with hot-spot mutation sites of c.C301T and c.G537A. Allogeneic HSCT is efficacious but has a high mortality rate (17.5%, 7 of 40). CONCLUSIONS: Our study expands the current knowledge on the genotype-correlated phenotypes with a defect of IL10 signaling. B-cell lymphoma was more frequent than would be expected in patients with IL10RB mutations. There may be a unique genetic architecture among Eastern Asia compared with other populations. Although allogeneic HSCT represents a causal therapeutic approach for IL10-and IL10R-deficient patients, a word of caution is warranted.

The characteristics of 83 giant peptic ulcers in Chinese children: Evaluation and follow-up.

BACKGROUND/AIMS: Giant peptic ulcers (GPUs) are detrimental for all patients, especially for children. However, few reports have described GPUs in children. This study aims to evaluate the characteristics of GPUs in Chinese children and to identify risk factors. PATIENTS AND METHODS: We retrospectively analyzed patients at the Children's Hospital of Fudan University from April 2014 to August 2017. Patients with GPUs (>2.0 cm) were included in the study, and the clinical data, pathological characteristics and presence of Helicobacter pylori (H. pylori) infection were analyzed to evaluate the outcomes. RESULTS: A total of 19208 children underwent gastroscopic examinations, and 83 patients with GPUs were enrolled. The mean age of onset for GPU patients was 9.7 ± 3.2 years(range, 1-15). The main complaints were abdominal pain (92.7%), anemia (53%), retching (45.8%), hematochezia (21.7%) and hematemesis (16.9%). With respect to the types of GPU, 68 patients (81.9%) had duodenal ulcers, and 15 patients (18.1%) had gastric ulcers. Compared to the group <6 years of age, the group ≥6 years was more susceptible to GPU (P < 0.05). Among GPU patients, 71.1% of cases were H. pylori (*) (59/83), and 16.9% (14/83) of patients were H. pylori (-). Compared to the H. pylori (-) group, the H. pylori (*) group showed inflammatory activity, atrophy and lymphoid follicular formation in the gastric mucosa (P < 0.05). CONCLUSIONS: This study suggests that GPUs are strongly associated with H. pylori infection in Chinese children. Duodenal ulcers are the main type of GPU in patients older than 6 years. Appropriate diagnosis, treatment and follow-up are necessary for children with GPUs.

Relationships Between Social Support, Loneliness, and Internet Addiction in Chinese Postsecondary Students: A Longitudinal Cross-Lagged Analysis.

Using the Internet has become one of the most popular leisure activities among postsecondary students in China. Concern about the large number of students using the Internet has led to an increase in research on the influencing factors of Internet addiction and the negative consequences caused by it. This short-term longitudinal study examined the associations among three dimensions of social support [objective support (OS), subjective support (SS), and support utilization (SU)], loneliness, and the four dimensions of Internet addiction (compulsive Internet use [CIU] & withdrawal from Internet addiction [WIA], tolerance of Internet addiction [TIA], time-management problems [TMPs], and interpersonal and health problems [IHPs]) in a Chinese sample. A total of 169 postsecondary first-year students (88 girls and 81 boys; mean age = 18.31 years) participated in the study. The questionnaire measurements were taken at the beginning of the school year (T1), 6 months later (T2), and 1 year later (T3). Cross-lagged and structural equation modeling analyses indicated that (a) OS (T1) and SU (T1) negatively predicted loneliness (T2); and loneliness (T2) negatively predicted OS (T3) and SU(T3); (b) CIU & WIA (T1) and TMPs (T1) positively predicted loneliness (T2); and loneliness (T2) positively predicted CIU & WIA (T3), TIA (T3), TMP (T3), and IHP (T3); (c) SS (T1) directly affected TIA (T3) and TMP (T3); and (d) loneliness (T2) played a mediating role in the relationships between OS (T1) and CIU (T3), OS (T1) and TMP (T3), OS (T1) and IHP (T3), and SU (T1) and IHP (T3). Finally, interventions for Internet addiction and implications for future studies were discussed.

A20 inhibits lipopolysaccharide-induced inflammation in enterocytes.

AIM: To examine the role of A20 in the regulation of intestinal epithelial cells (IECs) inflammation. METHODS: Using gene transfection, both stable overexpression and knockdown A20-expressed HT-29 cell lines were established. Accordingly, the cells were divided into the following groups: The control group, the A20 overexpression group, the A20 knockdown group and the respective controls. A20 was stimulated with lipopolysaccharide (LPS) in a dose- and time-dependent manner and was detected using western blotting and real-time polymerase chain reaction (PCR) analyses. Immunofluorescence and western blotting analyses were performed to investigate the role of A20 in the regulation of nuclear factor (NF)-κB activation and translocation into the nucleus. ELISA and real-time PCR were performed to examine A20 in regulating the release of the following inflammatory cytokines: Tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6 and IL-8. RESULTS: The expression of A20 in IECs was inducible. When intestinal epithelial cells were subjected to the stimulation of LPS, the expression of A20 was increased, and the expression of A20 was induced in a dose- and time-dependent manner. The expression of A20 was very low in HT-29 cells without LPS stimulation but rapidly increased and was maintained at a high level 2-4 h after stimulation with LPS. These levels gradually declined with a change in time-course, and the expression of A20 increased with increasing LPS stimulation. Western blotting and immunofluorescence revealed that overexpression of A20 can inhibit NF-κB activation and its translocation to the nucleus. The overexpression of A20 can reduce the levels of proinflammatory cytokines involved in the pathophysiology of inflammatory bowel disease. There was no significant difference in the expression of IL-8 mRNA in the control group, A20 overexpression group or A20 knockdown group without LPS stimulation (P > 0.05); however, while after 2 h, 4 h and 8 h stimulation with LPS, the expression of IL-8 in the A20 overexpression group was lower than the control group and the A20 knockdown group (P < 0.05 or P < 0.01). The expression of TNF-α was different at different time points after 8 h of LPS stimulation (F = 31.33, DF = 5, P < 0.001), and the expression of TNF-α increased as the LPS stimulation time increased. Upon LPS stimulation, lower levels of TNF-α were detected in the A20 overexpression cell lines (P < 0.05). There were no significant differences in the induction of IL-6 and IL-1ß among the control group, A20 overexpression group and A20 knockdown group (P > 0.05). CONCLUSION: A20 plays an important role in limiting inflammation by inhibiting LPS-induced NF-κB responses in the gut luminal. A20 may be a potential therapeutic tool for inflammatory diseases.