SLCO1B1 and SLCO1B3 genetic mutations in Taiwanese patients with Rotor syndrome.

Rotor syndrome is a rare, benign, inherited disorder that is commonly associated with mild hyperbilirubinemia. It is caused by bi-allelic pathological variants in both SLCO1B1 and SLCO1B3 genes, causing defective OATP1B1 and OATP1B3 in the sinusoidal membrane and interrupted bilirubin uptake of the hepatocytes. We report five Taiwanese pediatric and adult patients aged 5-32 years presenting with conjugated hyperbilirubinemia, and were found to have genetic variants of SLCO1B1 and SLCO1B3. Two also had history of prolonged neonatal jaundice. Genetic analysis using panel-based next generation sequencing revealed three patients with homozygous mutations c.1738C>T (p.R580∗) in SLCO1B1 and a transposon LINE-1 insertion in SLCO1B3, one patient with homozygous mutations for another haplotype, c.757C>T (p.R253∗) in SLCO1B1 and c.1747+1G>A in SLCO1B3. Another patient had heterozygous c.1738C>T (p.R580∗) in SLCO1B1 linked with a LINE-1 insertion in SLCO1B3, and heterozygous c.757C>T (p.R253∗) in SLCO1B1 linked with c.1747+1G>A in SLCO1B3. In conclusion, we present the first time of genetic diagnosis of Rotor syndrome in Taiwan. Advanced genetic testing has enhanced the diagnosis of rare diseases with mild symptoms.

A survey among healthcare professionals from seven countries reported diverse nutritional practices of late preterm infants.

AIM: To gain insight into nutritional practices and expected growth outcomes of infants born between 34 and 36 gestational weeks defined as late preterm infants (LPT). METHODS: An anonymous online survey among paediatricians and neonatologists from Bangladesh, Indonesia, Mexico, Nigeria, Malaysia, Singapore and Taiwan was conducted from March until October 2020. The questionnaire consisted of 40 questions on the nutritional management and expected growth outcomes of LPT in and after-hospital care. RESULTS: Healthcare professionals from low to high Human Development (HDI) countries (n = 322) and very high HDI countries (n = 169) participated in the survey. Human milk was the preferred feeding, resulting in an adequate growth of LPT (weight, length and occipitofrontal circumference), according to a majority of respondents (low to high HDI, 179/265, 68% vs. very high HDI, 73/143, 51%; p = 0.002). The expected growth outcome was higher after-hospital discharge. Less than half of healthcare professionals started enteral feeding during the 1st hour of life. Lactation difficulties, limited access to human milk fortifiers and donor human milk, especially among low to high HDI countries, were reported as major hurdles. CONCLUSION: Human milk is the first feeding choice for LPT. The diverse opinions on nutritional practices and expected growth outcomes among healthcare professionals indicate the necessity to develop general nutritional guidelines for LPT.

Modulations of probiotics on gut microbiota in a 5-fluorouracil-induced mouse model of mucositis.

BACKGROUND AND AIM: Intestinal mucositis remained one of the most deleterious complications in cancer patients undergoing chemotherapy. 5-FU treatment was reported to affect the abundance of gut microbiota and cause mucositis, which might be ameliorated by probiotics. We investigate the potential changes of 5-FU treatment and the modulations of probiotics on gut microbiota in a mouse model. METHODS: Male BALB/c mice received either 5-FU or saline (S). They were separated and fed saline, Lactobacillus casei variety rhamnosus (Lcr) and Lactobacillus reuteri DSM 17938 (BG). Lcr and BG were simultaneously administered with 5-FU for 5 days. Stool specimens were collected for DNA extraction and pyrosequenced for bioinformatic analysis. RESULTS: Fecal microbial communities were obviously diverse. Bacteroides and Bacteroidaceae were the most abundant microbiota in FU.BG group while S24_7 was the most in S.S group. At phylum and class levels, abundances of Betaproteobacteria, Erysipelotrichi, Gammaproteobacteria, and Verrucomicrobia were significantly increased in the FU groups. Probiotics supplementation did increase the abundances of Enterobacteriales and Turicibacterales. We demonstrated that probiotics did modulate the abundance and diversity of gut microbiota. Bacterial motility proteins were found enriched and upregulated in the S.BG group. No mortality was noted. No bacterial translocation was found in spleen and blood among the six groups. CONCLUSION: Gut microbiota of mice undergoing chemotherapy exhibited a distinct disruption in bacterial composition. Probiotic did modulate the abundance and diversity of gut microbiota. This is the first study to analyze the effects and safety of Lactobacillus strains on 5-FU-induced mucositis systematically and assess changes in the intestinal microbiota after probiotic intervention.

Epidemiology of Pediatric Acute Pancreatitis in Taiwan: A Nationwide Population-based Study.

OBJECTIVE: Pediatric acute pancreatitis (AP) may be different from adult AP in various respects. This study focuses on the epidemiology and medical resource use of pediatric AP in Taiwan. METHODS: Patients aged 0 to 18 years with AP were identified from the Taiwan National Health Insurance Research Database based on the International Classification of Diseases, Ninth Revision code of AP 577.0. The medical resource use was measured by length of hospital stay and hospital charges. RESULTS: Between 2000 and 2013, a total of 2127 inpatient cases of pediatric AP were collected, which represented a hospitalization rate of 2.83 per 100,000 population. The incidence by age had 2 peaks, the first peak was at age 4 to 5 years old, and the second one started rising from 12 to 13 years old until adulthood. The incidence by year increased from 2.33 to 3.07 cases per 100,000 population during the study period. The average hospital stay is steady, but the medical cost is increasing. Girls have longer hospital stays, higher medical expenditures, more use of endoscopic retrograde cholangiopancreatography possibly due to more comorbidities with biliary tract diseases than boys (P < 0.05). The mortality in cases of AP is mostly associated with systemic diseases rather than AP itself. CONCLUSIONS: The incidence of pediatric AP in Taiwan is in a rising trend. There are gender differences in length of hospital stay, medical costs, use of endoscopic retrograde cholangiopancreatography and comorbidities.

Quantitative maternal hepatitis B surface antigen predicts maternally transmitted hepatitis B virus infection.

Despite immunoprophylaxis, hepatitis B virus (HBV) transmission in highly viremic mothers remains a global health issue. Using quantitative maternal surface antigen (HBsAg) to predict HBV infection in infants has not been investigated. We enrolled 526 mother-infant pairs with positive maternal HBsAg under current immunoprophylaxis. Maternal viral load and quantitative HBsAg were measured in the peripartum period. Infant HBsAg seropositivity for more than 6 months was defined as chronic infection. Rates of chronic infection in infants at various maternal HBsAg levels were estimated using a multivariate logistic regression model. Results showed that maternal HBsAg was positively correlated with maternal viral load (r = 0.69; P < 0.001) and accurately predicted maternal viral load above 6, 7, and 8 log10 IU/mL with an area under the receiver operating characteristic curve (AUC) of 0.97, 0.98, and 0.95. Nineteen infants were chronically infected. After adjustment for the other risk factor, maternal HBsAg level was significantly associated with risk of infection (adjusted odds ratio for each log10 IU/mL increase, 15.02; 95% confidence interval [CI], 3.89-57.94; P < 0.001). The AUC for predicting infection by quantitative maternal HBsAg was comparable to that by maternal viral load (0.89 vs. 0.87; P = 0.459). Estimated rates of infection at maternal HBsAg levels of 4, 4.5, and 5 log10 IU/mL were 2.4% (95% CI, 0.1-4.6; P = 0.04), 8.6% (95% CI, 4.5-12.7; P < 0.001), and 26.4% (95% CI, 12.6-40.2; P < 0.001). CONCLUSION: Quantitative maternal HBsAg predicts infection in infants as well as maternal viral load does. Antiviral therapy may be considered in pregnant women with an HBsAg level above 4-4.5 log10 IU/mL to interrupt mother-to-infant transmission. (Hepatology 2016;64:1451-1461).

Quality improvement of pediatric colonoscopy by application of bundle and centralization: A single-center review.

BACKGROUND: To assess the quality change of our single-center pediatric colonoscopy after applying bundle for bowel preparation and general anesthesia and centralize the procedure using terminal ileum (TI) intubation rate as the main indicator. METHODS: All elective colonoscopies performed for patients younger than 18 years old in MacKay Memorial Hospital from July 2015 through June 2020 (assigned to group 1, before bundle) and from August 2020 through July 2021 (assigned to group 2, after bundle) were retrospectively reviewed for demographic characteristics, indications, bowel preparation agent and cleansing level, diagnostic and therapeutic procedures, maximum intestinal level reached, and cecal intubation and total procedure time. Statistical analysis was done using P value < 0.05 considered to be significant. RESULTS: Analysis included 45 and 32 colonoscopies in group 1 and 2, respectively. Bloody stool was the most frequent indication in both groups. Both TI intubation rate (42.2 % vs. 75.0 %, P = 0.004) and biopsy rate (45.0 % vs. 75.9 %, P = 0.01) increased significantly from group 1 to group 2. The narrower standard deviation of bowel preparation score (1.93 vs. 1.15) and total procedure time (37.71 vs. 22.29) in group 2 indicated a more stable quality, although the mean showed no difference. There was no statistical difference in age, gender, body weight, cecal intubation rate, or cecal intubation time. CONCLUSION: A higher TI intubation rate and biopsy rate indicated an improved quality of pediatric colonoscopy after applying bundle including bowel preparation and general anesthesia, with additional centralization.

Localization and Laparoscopic Excision of Gastric Heterotopic Pancreas in a Child by Endoscopic SPOT® Tattooing.

Heterotopic pancreas (HP) is defined as pancreatic tissue lacking vascular or anatomic connection with the normal pancreas. Surgical resection is often indicated for symptomatic gastric HP. However, intraoperative identification of gastric HP is often difficult during laparoscopic surgery. Herein, we describe a patient with gastric HP, which was marked with SPOT® dye (GI Supply, Camp Hill, PA, USA). The dye was seen clearly laparoscopically facilitating total excision of the lesion. The final pathology report confirmed the presence of heterotopic pancreatic tissue including pancreatic acini, small pancreatic ducts tissue with islets of Langerhans in the deep gastric submucosal area. There were no postoperative complications, and the patient was symptom-free. To the best of our knowledge, this was the first case report in the literature in which endoscopic tattooing of gastric HP before laparoscopic resection was performed. This method of localization was simple and reliable in children.

Genetic variability of interleukin4 gene in Taiwanese children with biliary atresia.

Biliary atresia (BA) is a neonatal cholangiopathy of unknown etiology that leads to biliary cirrhosis and is the most common cause of liver transplantation in children. A still undetermined hepatobiliary viral infection may elicit an uncontrollable autoimmune response against the biliary epithelial cells in genetically predisposed children and culminates in atresia of the biliary trees. Interleukin 4 (IL4) is crucial for the differentiation of naive T helper cells into the T helper 2 effector cells that promote humoral immunity. This study aims to investigate whether polymorphisms of the IL4 gene are associated with susceptibility to BA. Genomic DNA was extracted from whole blood samples of 53 Taiwanese children with BA and 904 ethnically-matched healthy controls. The IL4 -590 C/T, -33 C/T, and 8375 A/G polymorphisms were genotyped using the Pre-Developed TaqMan Allelic Discrimination Assay in a real-time polymerase chain reaction system. No significant difference between children with BA and healthy controls were found when comparing genotype, allele, carrier, and haplotype frequencies of these IL4 gene variants. These results suggest that the tested polymorphisms of IL4 gene are unlikely to contribute significantly to BA susceptibility in Taiwanese children.

Different clinical manifestations between primary gastrointestinal malignancies and benign tumors in children.

OBJECTIVE: The purpose of the present study was to review the different clinical manifestations of primary gastrointestinal (GI) malignancies and benign tumors in pediatric patients. METHODS: The demographic data, duration to diagnosis, clinical features, laboratory data, location and pathology of the tumors, and outcomes of pediatric patients from January 1984 to December 2009 were retrospectively reviewed. RESULTS: A total of 24 GI malignancies and 62 benign tumors were diagnosed. Patients in the benign group were mostly diagnosed in the first decade of life (73%), whereas majority of patients with malignancies were older than 10 years (79%). The most common tumor location in the benign group was the colorectum, whereas in the malignant group, tumors were distributed equally in the small intestine and colorectum. The median duration from onset to diagnosis in the benign group was longer than that of the malignant group (P>00.05). There was statistically significant increase in the presence of hematochezia in patients with benign tumor compared with those with malignancy (P<00.05). Among the malignancies, 79% presented with abdominal pain, followed by weight loss (25%), anorexia (25%), palpable mass (25%), and fever (21%), with statistically significant differences compared with the benign group (P<00.05). Anemia was found in 47% to 63% of patients in both groups (P>00.05). Two patients with polyposis subsequently developed malignancy. CONCLUSIONS: Different manifestations of GI malignancies and benign tumors may help pediatricians to detect these early. Patients with polyposis should be aware of the risk of malignant change.

A rare case of pancreatic macrocystic serous cystadenoma in an adolescent: a case report and literature review.

While serous cystadenomas of the pancreas usually consist of small cysts, one rare variant has been reported to be composed of macrocysts. Herein, we present the case of the youngest patient with macrocystic serous cystadenoma (MSC) to be reported in the literature. The patient was a 17-year-old girl who presented with the major symptoms of a palpable abdominal mass accompanied by epigastric pain and vomiting for several months. A potential malignancy could not be excluded on the basis of imaging studies, which showed a large macrocystic pancreatic tumor that was 7 cm in diameter. Owing to the patient's symptoms, after diagnosing the mass as a pancreatic cystic tumor with potential malignancy and large tumor size, surgical intervention was arranged. Pathological analysis of the biopsy sample suggested MSC. By reviewing the literature, we found several unique characters of MSCs that cause them to be frequently misdiagnosed as potential malignancies. Additionally, the age of MSC occurrence was found to be lower than of general serous cystadenomas. The potential of MSC should be kept in mind by clinicians when diagnosing young people with pancreatic macrocystic lesions.

Blue Rubber Bleb Nevus Syndrome (BRBNS): A Rare Cause of Refractory Anemia in Children.

Refractory anemia is not uncommon in pediatric patients, and anemia caused by gastrointestinal tract bleeding should always be kept in mind. Aside from infection or intestinal malrotation related bleeding, vascular malformation should also be considered. Blue rubber bleb nevus syndrome (BRBNS) is a rare vascular disorder consisting of multiple venous malformations. Lack of experience in pediatric BRBNS might lead to delayed diagnosis or misdiagnosis. Herein, we report a case of an eleven-year-old boy with recurrent pallor appearance and weakness diagnosed with BRBNS. After a thorough examination, he was treated with endoscopic polypectomy, and further iron supplements and folic acid. He is now under regular follow-up at our outpatient department. No complication is noted for six months. BRBNS is a rare venous malformation syndrome that mostly involves skin and the gastrointestinal tract. Multidisciplinary approach should be arranged for diagnosis and management. Up to date, no consensus for BRBNS treatment has been reached. Management usually depends on clinical symptoms and severity of damage of involved organs. The options of treatment include conservative, medical, endoscopic, and surgical management.

Coexisting gastrointestinal and hepatobiliary tract anomalies in omphalocele and gastroschisis: A twenty-year experience in a single tertiary medical center.

BACKGROUND: Omphalocele and gastroschisis are the two most common congenital abdominal wall defects; however, no previous study has focused on gastrointestinal and hepatobiliary tract malformations in these two conditions. This study aimed to investigate the demographic characteristics, coexisting congenital gastrointestinal and hepatobiliary tract anomalies, hospital course, and outcomes of patients with gastroschisis and omphalocele. METHODS: This is retrospective chart review of all patients admitted to one tertiary medical center in Taiwan between January 1, 2000 and June 30, 2020 with a diagnosis of gastroschisis or omphalocele. The medical records were reviewed to obtain demographic data regarding coexisting gastrointestinal and hepatobiliary tract anomalies and outcomes. RESULTS: Of the 51 patients included, 21 had gastroschisis and 30 had omphalocele. Gastroschisis was associated with a significantly younger maternal age and a higher incidence of small for gestational age. Of the 30 patients with omphalocele, twelve had associated gastrointestinal and hepatobiliary anomalies. Seven of the 21 patients with gastroschisis had gastrointestinal anomalies, and none had hepatobiliary anomalies. Among the omphalocele patients, three (10%) had documented malrotation, and one developed midgut volvulus. Among gastroschisis patients, four patients (19%) had malrotation, and two developed midgut volvulus. There were no statistically significant differences in postoperative complications or mortality rates between those with and without gastrointestinal/hepatobiliary tract anomalies. CONCLUSION: The diversity of coexisting gastrointestinal and hepatobiliary tract anomalies is higher in the omphalocele than in gastroschisis. In addition, we demonstrate that patients with gastroschisis or omphalocele have a higher rate of intestinal malrotation and midgut volvulus.

Rare presentation in a rare case of pancreatic extraosseous Ewing's sarcoma: A case report.

RATIONALE: Extraosseous Ewing's sarcoma is a rare tumor which is aggressive with poor prognosis; it can occur anywhere in the body, but scantily in the pancreas. Pancreatic Ewing's sarcoma is not reported commonly, with inconsistent clinical manifestations. In this regard, early recognition of this disease is very important for the patient's sake. PATIENT CONCERNS: A 16-year-old boy presented with left lower quadrant abdominal pain for 2 months, and left flank pain with dysuria for 1 month. DIAGNOSIS: Abdominal and renal ultrasonography found a mass between the spleen and left kidney as well as left renal pelvic dilatation. Abdominal computed tomography found a heterogenous mass derived from the tail of the pancreas. Serial examinations revealed that the mass was a pancreatic Ewing's sarcoma. Furthermore, no metastasis was documented. INTERVENTIONS: The tumor was totally excised after 6 months of chemotherapy, which included 10 courses of neoadjuvant chemotherapy with vincristine, epirubicin, and cyclophosphamide, alternating with ifosfamide and etoposide. The patient completed consolidation chemotherapy with vincristine, epirubicin, and cyclophosphamide, alternating with ifosfamide and etoposide for 5 courses. Radiotherapy was applied to the tumor-involved region and tumor bed. OUTCOMES: To date, the malignancy has not recurred since the treatment was completed 4 years ago. There are no complications from the treatment for the patient. LESSONS: The pancreas is a very rare extraosseous location for Ewing's sarcoma. Pancreatic extraosseous Ewing's sarcoma should be regarded as a differential diagnosis of non-urinary originated left flank pain with dysuria in adolescents.

A novel mutation in PYCR1 causes an autosomal recessive cutis laxa with premature aging features in a family.

The autosomal recessive form of type II cutis laxa (ARCL II) is characterized by the appearance of redundant, inelastic skin with wrinkling, an aged look and additional variable systemic involvement including intrauterine growth retardation, failure to thrive, developmental delay, dysmorphism, osseous abnormality, and CNS manifestations. Several genetic defects have been found in patients and families with the clinical manifestations of ARCL II. Recently, mutations in PYCR1 have been linked to cutis laxa with progeroid features. We ascertained two siblings with of ARCL II born to non-consanguineous parents. Mutation analysis of PYCR1 revealed a novel single-base deletion (c.345delC) in exon 4 leading to frame-shift and premature stop of translation. The effect of this mutation results in a strong reduction of PYCR1 expression in skin fibroblasts from affected siblings. These two cases extend the genotypic spectrum of PYCR1-related ARCL II.

Compound heterozygous mutations in PYCR1 further expand the phenotypic spectrum of De Barsy syndrome.

De Barsy syndrome (DBS) is characterized by progeroid features, ophthalmological abnormalities, intrauterine growth retardation, and cutis laxa. Recently, PYCR1 mutations were identified in cutis laxa with progeroid features. Herein, we report on a DBS patient born to a nonconsanguineous Chinese family. The exceptional observation of congenital glaucoma, aortic root dilatation, and idiopathic hypertrophic pyloric stenosis in this patient widened the range of symptoms that have been noted in DBS. Mutation analysis of PYCR1 revealed compound heterozygous PYCR1 mutations, including a p.P115fsX7 null mutation allele and a second allele with two missense mutations in cis: p.G248E and p.G297R. The effect of mutation results in a reduction of PYCR1 mRNA expression and PYCR1 protein expression in skin fibroblasts from the patient. The findings presented here suggest a mutation screening of PYCR1 and cardiovascular survey in patients with DBS.

Association of polymorphisms in the Interleukin-18 gene with susceptibility to biliary atresia.

BACKGROUND AND OBJECTIVE: Biliary atresia (BA) is a destructive inflammatory obliterative cholangiopathy of neonates that affects both intrahepatic and extrahepatic bile ducts. Although the etiology is unknown, immunologically mediated injury of the bile ducts triggered by as yet unidentified infectious agents is likely to play a critical role. Interleukin-18 (IL-18) is a proinflammatory cytokine that plays an important role in immune, infectious, and inflammatory diseases because of its induction of interferon-gamma. In this study, we investigated whether polymorphisms of the IL18 gene were associated with susceptibility to BA. PATIENTS AND METHODS: Genomic DNA was extracted from whole-blood samples of 50 Taiwanese children with BA and 1117 ethnically matched healthy controls. The IL18 -1297 T/C, -607 C/A, -137 G/C, and +105 A/C polymorphisms were genotyped using the TaqMan assay. RESULTS: No statistically significant differences of genotype, allele, carrier, and haplotype frequencies of these IL18 gene variants were found between children with BA and healthy controls. CONCLUSIONS: Our data suggest that the IL18 gene does not play a major role in BA predisposition in Taiwanese children.

Recent advance in infant nutrition: Human milk oligosaccharides.

Breast feeding and human milk are the standards for infant feeding and nutrition. Human milk oligosaccharides (HMOs) are the third most abundant solid component in human milk. To date, more than 200 structural different HMOs have been identified and some can be synthesized by the food industry. HMOs are one of the major differences between human milk and formula milk, and current evidence demonstrates their various beneficial effects toward infants' health: acting as anti-adhesive antimicrobials, immune modulators, and intestinal cell response modulators, as well as providing prebiotics effect and neurodevelopment and cognition effects. HMOs compositions vary among mothers, influenced by the stage of lactation, duration of pregnancy and maternal genetic factors. However, there are still some unknown factors affecting the compositions of HMOs and requiring further research for clarification. A combination of preclinical and clinical cohort studies may help to identify whether an individual HMO contributes to disease protection. In recent years, 2'-fucosyllactose (2'-FL) and lacto-N-neotetraose (LNnT) have been approved as food ingredients by official authorities. Infant formulae supplemented with these HMOs are well-tolerated. However, more prospective clinical studies are warranted to elucidate HMOs' significance in infant nutrition. Breast milk feeding remains the best option for infants nutrition and development. Whenever breast milk is not adequate or unavailable, infant formula supplemented with HMOs might be considered as an alternative.

Immune Modulation Effects of Lactobacillus casei Variety rhamnosus on Enterocytes and Intestinal Stem Cells in a 5-FU-Induced Mucositis Mouse Model.

BACKGROUND: Intestinal mucositis remains one of the most deleterious side effects in cancer patients undergoing chemotherapy. We hypothesize that the probiotics could preserve gut ecology, ameliorate inflammation, and protect epithelia via immune modulations of enterocytes and intestinal stem cells. Our aim is to characterize these changes and the safety of probiotics via a 5-fluorouracil- (5-FU-) induced intestinal mucositis mouse model. METHODS: 5-FU-injected BALB/c mice were either orally administrated with saline or probiotic suspension of Lactobacillus casei variety rhamnosus (Lcr35). Diarrhea scores, serum proinflammatory cytokines, and T-cell subtypes were assessed. Immunostaining analyses for the proliferation of intestinal stem cells CD44 and Ki67 were processed. Samples of blood and internal organs were investigated for bacterial translocation. RESULTS: Diarrhea was attenuated after oral Lcr35 administration. Serum proinflammatory cytokines were significantly increased in the 5-FU group and were reversed by Lcr35. A tremendous rise of the CD3+/CD8+ count and a significant decrease of CD3+CD4+/CD3+CD8+ ratios were found in the 5-FU group and were both reversed by Lcr35. 5-FU significantly stimulated the expression of CD44 stem cells, and the expression was restored by Lcr35. 5-FU could increase the number of Ki67 proliferative cells. No bacterial translocation was found in this study. CONCLUSIONS: Our results showed that 5-FU caused intestinal inflammation mainly via Th1 and Th17 responses. 5-FU could stimulate stem cells and proliferation cells in a mouse model. We demonstrate chemotherapy could decrease immune competence. Probiotics were shown to modulate the immune response. This is the first study to analyze the immune modulation effects and safety of Lactobacillus strain on enterocytes and intestinal stem cells in a mouse model.

Effects of Vitamin D-Deficient Diet on Intestinal Epithelial Integrity and Zonulin Expression in a C57BL/6 Mouse Model.

Background and Aims: Vitamin D (VD) plays an important role not only in mineral balance and skeletal maintenance but also in immune modulation. VD status was found correlated with the pathophysiology and severity of inflammatory bowel diseases and other autoimmune disorders. Epithelial barrier function is primarily regulated by the tight-junction (TJ) proteins. In this study, we try to establish an animal model by raising mice fed VD-deficient diet and to investigate the effects of VD-deficient diet on gut integrity and zonulin expression. Methods: Male C57BL/6 mice were administered either VD-deficient [VDD group, 25(OH)2D3 0 IU/per mouse] or VD-sufficient [VDS group, 25(OH)2D3 37.8 IU/per mouse] special diets for 7 weeks. Body weight and diet intake were recorded weekly. Serum VD levels were detected. After sacrifice, jejunum and colon specimens were collected. The villus length and crypt depth of the jejunum as well as mucosa thickness of the colon were measured. Various serum pro-inflammatory cytokines and intestinal TJ proteins were assessed. The serum level of zonulin and the mRNA expression of jejunum zonulin were also investigated. Results: We found that mice fed a VDD diet had a lower serum level of VD after 7 weeks (p < 0.001). VDD mice gained significant less weight (p = 0.022) and took a similar amount of diet (p = 0.398) when compared to mice raised on a VDS diet. Significantly decreased colon mucosa thickness was found in VDD mice compared with the VDS group (p = 0.022). A marked increase in serum pro-inflammatory cytokine levels was demonstrated in VDD mice. All relative levels of claudin (CLD)-1 (p = 0.007), CLD-3 (p < 0.001), CLD-7 (p < 0.001), and zonulin-1 (ZO-1, p = 0.038) protein expressions were significantly decreased in the VDD group when compared to the VDS group. A significant upregulation of mRNA expression of jejunum zonulin (p = 0.043) and elevated serum zonulin (p = 0.001) were found in the VDD group. Conclusions: We successfully demonstrated that VDD could lead to impaired barrier properties. We assume that sufficient VD could maintain intestinal epithelial integrity and prevent mucosal barrier dysfunction. VD supplementation may serve as part of a therapeutic strategy for human autoimmune and infectious diseases with intestinal barrier dysfunction (leaky gut) in the future. To our knowledge, this is the first study to demonstrate that VDD could lead to a significant upregulation in mRNA expression of the jejunum zonulin level and also a marked elevation of serum zonulin in a mouse model.