Lili Gu

Visceral fat area is associated with a high risk for early postoperative recurrence in Crohn's disease.

Mesenteric hypertrophy has been recognized as an indicator of the complicated course of Crohns disease. The aim of this study was to investigate whether the visceral fat area (VFA) is associated with postoperative clinical and endoscopic recurrence.

Exclusive enteral nutrition ameliorates mesenteric adipose tissue alterations in patients with active Crohn's disease

BACKGROUND & AIMS Mesenteric adipose tissue hypertrophy is a hallmark of Crohns disease and can express various adipokines. Exclusive enteral nutrition could effectively induce remission in Crohns disease with mechanisms largely unknown. We investigated whether exclusive enteral nutrition could modify mesenteric fat in patients with active Crohns disease. METHODS Sixteen patients who underwent resection for ileum Crohns disease were studied. As a control group, eight patients without inflammatory bowel disease were enrolled. Before operation, eight Crohns disease patients received exclusive enteral nutrition for four weeks, and the other patients had no nutritional therapy. The mesenteric fat samples were obtained during operation. Adipocyte size, adipokine production and topical C-reactive protein level were assessed. RESULTS The adipocyte size from patients treated with exclusive enteral nutrition was much larger than that from Crohns disease patients without nutritional therapy. Furthermore, protein levels of proinflammatory adipokines such as TNF-alpha and leptin were lower while protein level of adiponectin was higher in these patients. As to mRNA level, the expression of adiponctin was up-regulated and leptin was down-regulated in the patients received enteral nutrition. CONCLUSIONS Exclusive enteral nutrition could ameliorate mesenteric fat alterations which are associated with intestinal injury in patients with Crohns disease by restoring adipocyte morphology and diminishing the inflammatory environment of mesenteric fat.

Celastrol ameliorates experimental colitis in IL-10 deficient mice via the up-regulation of autophagy.

BACKGROUND Celastrol had been proved effective in the treatment for IBD, probably with the modulation of oxidative stress, inflammatory cytokines and intestinal homeostasis. This study was aimed to investigate whether celastrol could ameliorate the inflammation of IL-10 deficient mice, a murine model of Crohns disease (CD) with the induction of autophagy. MATERIAL AND METHODS The mice included were divided into four groups, ##WT group, IL-10(-/-) group, Cel group and Control group (celastrol+3-Methyladenine). Celastrol (2 mg/kg) treatment by gavage was administered to mice daily over one week. 3-Methyladenine (autophagy inhibitors) was administered at a dose of 30 mg/kg by intraperitoneal injection. The histological evaluation of the colon, tissue myeloperoxidase (MPO), and colon inflammation of mice in the four groups was evaluated and compared. Furthermore, the PI3K/Akt/mTOR pathway and the status of autophagy in intestine affected by celastrol were also assessed. RESULTS The one-week administration of celastrol ameliorated established colitis in IL-10 deficient mice, associated with a reduction of marked histological inflammation, a decreased colon MPO concentration and suppression of colonic proinflammatory cytokine. Furthermore, the decreased neutrophil infiltration in proximal colon and improvement of inflammation in the Cel group was much more obvious than that in the Control group. The Western blotting analysis of the PI3K/Akt/mTOR pathway and autophagy showed that celastrol treatment up-regulated the autophagy of colon tissue by suppressing the PI3K/Akt/mTOR signaling pathway. CONCLUSIONS Celastrol ameliorates experimental colitis in IL-10 deficient mice via the up-regulation of autophagy by suppressing the PI3K/Akt/mTOR signaling pathway.

Cigarette smoking is associated with intestinal barrier dysfunction in the small intestine but not in the large intestine of mice

AIMS To observe the effect of cigarette smoke (CS) on the small bowel and colon in mice and to attempt to explain the potential mechanisms that account for these effects. METHODS Male BALB/c mice age 6-8 weeks were randomly divided into a CS group and a control group (n=10 per group). CS mice were exposed to CS (five cigarettes each time, four times a day for 5 days a week using Hamburg II smoking machine and CS was diluted with air at a ratio of 1:6) for 10 weeks, and control mice were exposed to room air. After 10 weeks, mice were sacrificed for analysis (colon and small bowel). RESULTS CS exposure impaired the intestinal barrier of the small bowel, based on evidence that CS mice exhibited increased intestinal permeability, bacterial translocation, intestinal villi atrophy, damaged tight junctions and abnormal tight junction proteins. These changes were partly mediated through the activated NF-κB (p65) signalling pathway. However, no obvious changes associated with the intestinal barrier were identified in the small bowel of control mice or the colons of control or CS mice. CONCLUSIONS CS is associated with intestinal barrier dysfunction in the small intestine but not in the large intestine of mice.

Oral treatment with SEW2871, a sphingosine-1-phosphate type 1 receptor agonist, ameliorates experimental colitis in interleukin-10 gene deficient mice

SEW2871, a selective sphingosine‐1‐phosphate type 1 receptor (S1P1) agonist, has been shown to be effective in protecting kidneys against ischaemia–reperfusion injury by reducing CD4+ T cell infiltration in mice. However, the effects of SEW2871 on colitis remain unclear. The aim of this study was to investigate the effects of SEW2871 on established colitis in interleukin (IL)‐10 gene‐deficient (IL‐10–/–) mice, a murine model of Crohns disease (CD). SEW2871 was administered by gavage at a dose of 20 mg/kg/day for 2 weeks to IL‐10–/– mice. Severity of colitis, serum amyloid A, tissue myeloperoxidase (MPO), T cells in blood and colon lamina propria (LP) and proinflammatory cytokine productions were evaluated. Furthermore, the phospho‐signal transducer and activator of transcription (STAT)‐3 (p‐STAT‐3) expression in lymphocytes isolated from colon LP was also assessed. The 2‐week administration of SEW2871 ameliorated established colitis in IL‐10–/– mice, associated with a reduction of serum amyloid A concentration, a decreased colon MPO concentration, a depletion of the peripheral CD4+CD45+ T cells and a reduction of the homing of T cells into colon LP. Moreover, typical cytokines of T helper type 1 (Th1) and Th17 cells and p‐STAT‐3 expression were also suppressed by SEW2871 treatment. SEW2871 treatment ameliorates established experimental colitis in IL‐10–/– mice, which may provide a new therapeutic approach for human CD therapy.

Stapled vs hand suture closure of loop ileostomy: a meta-analysis

Loop ileostomies are widely used in colorectal surgery to reduce the consequences of distal anastomotic failure. The optimal surgical technique for their closure has yet not been defined. A meta‐analysis was performed to compare the outcome after stapled or hand sutured ileostomy closure.

Treatment of Slow Transit Constipation With Fecal Microbiota Transplantation: A Pilot Study

Background: Fecal microbiota transplantation (FMT) has been proposed as a therapeutic approach for functional gastrointestinal disease. We launched a clinical study to examine the safety and efficacy of FMT for slow transit constipation (STC). Materials and Methods: Twenty-four patients with STC, aged from 20 to 74 were enrolled in this prospective open-label study. Patients received FMT on 3 consecutive days through nasojejunal tubes and followed up for 12 weeks after treatment. Rate of clinical improvement and remission, Wexner constipation scale, Bowel movement per week, and gastrointestinal quality-of-life index were evaluated. Results: The rate of clinical improvement and remission based on clinical activity at week 12 was 50% (12/24) and 37.5% (9/24), respectively. The patient’s stool frequency increased from a mean of 1.8 (SD 1.3) per week pre-FMT to 4.1 (SD 2.6) at week 12 post-FMT without laxative usage (P<0.01). The stool consistency showed a tendency to improve after FMT administration. Comparison of pre-FMT and post-FMT Wexner constipation scores demonstrated a significant reduction between baseline (14.1±3.3) and the first week (9.8±4.9), which was maintained up to the following 12 weeks (7.5±3.2; P<0.01). Compared with baseline, significant overall improvements were also seen in gastrointestinal quality-of-life index score at week 1, week 2, week 4, week 8, and week 12 of follow-up (P<0.01). The improvements were accompanied by the decline of colonic transit time. No severe adverse events during the whole FMT procedure follow-up except for venting (6/24), abdominal pain (3/24), bloating (2/24), and diarrhea (7/24). Conclusion: This is a pilot study demonstrating that FMT was safe and may have the potential to improve symptoms in patients with STC.

Role of Exclusive Enteral Nutrition in the Preoperative Optimization of Patients With Crohn's Disease Following Immunosuppressive Therapy

AbstractWe conducted a study to evaluate the impact of the exclusive enteral nutrition (EEN) on perioperative outcome in Crohns disease (CD) patients following immunosuppressive therapy.Patients with CD followed at a referral center between January 2001 and March 2014 who underwent abdominal surgery were identified. Patients were divided into 4 groups: patients not exposed to immunosuppressive agents in the previous 8 weeks before surgery (group 1); patients received immunosuppressive medications without preoperative drug-free interval (group 2); patients had preoperative immunosuppressants-free interval (group 3); patients treated with adding EEN to preoperative immunosuppressants-free interval regimen (group 4). Urgent operation requirement, stoma creation, postoperative complications, readmission, and reoperation were compared in patients among groups.Overall, 708 abdominal surgeries performed in 498 CD patients were identified. Three hundred seventy-six (53.11%) surgeries performed in those receiving preoperative immunosuppressive medications. Compared with other groups, group 2 had increased postoperative complications, more frequent urgent operation, and higher rate of stoma creation. Patients in group 4 were found to have better outcome including lower rate of stoma creation (P < 0.05), and decreased incidence of postoperative complications (P < 0.05) compared with group 2 and group 3. Additionally, decreased urgent operation requirement (P < 0.05) and extended preoperative drug-free interval (P < 0.001) were observed in the group 4 than those in the group 3.Preoperative optimization of CD following immunosuppressive therapy by EEN prolongs the immunosuppressants-free interval, reduces the risk of urgent surgery and reoperation, and most importantly, decreases complications after abdominal surgery.

Influence of exclusive enteral nutrition therapy on visceral fat in patients with Crohn's disease.

Background:Mesenteric fat plays an important role in the pathogenesis of Crohns disease (CD), and a higher ratio of visceral fat area (VFA) to subcutaneous fat area (SFA) is related to complicated disease status. Exclusive enteral nutrition (EEN) is an effective treatment option for patients with CD, and the aims of this study were to assess the effects of EEN on abdominal fat in patients with CD. Methods:Patient data were obtained from a prospectively maintained database. The SFA and VFA were measured in 38 patients with CD before and after 8-week EEN therapy, and the mesenteric fat index (MFI), defined as the ratio of VFA to SFA, was calculated. The correlations between MFI and CD activity index and C-reactive protein level were also evaluated. Results:The median age of the patients in our study was 29 years, and the median duration of disease was 3.05 years. Both VFA (P = 0.029) and MFI (P = 0.021) were significantly decreased in patients after EEN, but no significant change was observed in SFA (P = 0.335). MFI was significantly correlated with CD activity index (r = 0.523, P = 0.001) and C-reactive protein (r = 0.634, P < 0.0001) in patients with active CD before EEN, although no positive correlations were observed in patients after EEN treatment. Conclusions:EEN induction therapy was associated with a significant decrease in VFA in patients with CD, and MFI was significantly correlated with CD activity index and C-reactive protein in active CD. Thus, our data reveal additional beneficial therapeutic mechanisms of enteral nutrition treatment in CD.

Tripterygium wilfordii Hook. f. versus azathioprine for prevention of postoperative recurrence in patients with Crohn's disease: a randomized clinical trial.

BACKGROUND Tripterygium wilfordii Hook. f. (TwHF) has been used for many years to induce the remission of Crohns disease in China. AIMS To compare TwHF versus azathioprine for the prevention of postoperative recurrence in Crohns disease. METHODS 90 Crohns disease patients who had undergone resection were treated with TwHF 1.5mg/kg/day or azathioprine 2.0 mg/kg/day. The primary endpoint was clinical recurrence, and the secondary endpoint was endoscopic recurrence. RESULTS 47 patients completed the trial. Clinical recurrence was observed in 6/45 patients in the TwHF group and 4/45 patients in the azathioprine group at week 26 (P=0.74). At week 52, 8/45 azathioprine patients and 12/45 TwHF patients had clinical recurrence (P = 0.45). During the first 26 weeks, 56.8% of the patients in the TwHF group versus 47.7% in the azathioprine group experienced endoscopic recurrence (P = 0.52). However, at week 52, 74.4% of patients in the TwHF group and 50% in the azathioprine group had endoscopic recurrence (P = 0.03). CONCLUSIONS TwHF was less effective in maintaining endoscopic remission at week 52, even though TwHF was comparable to azathioprine for preventing postoperative clinical recurrence.