The incidence of inflammatory bowel diseases is increasing worldwide, suggesting a potential role for dietary factors. Here, we demonstrate that a high fructose diet worsens colitis in a microbiota-dependent manner. Overall, this study highlights the importance of diet-microbe interactions in intestinal inflammation. BACKGROUND & AIMS: The incidence of inflammatory bowel diseases has increased over the last half century, suggesting a role for dietary factors. Fructose consumption has increased in recent years. Recently, a high fructose diet (HFrD) was shown to enhance dextran sodium sulfate (DSS)-induced colitis in mice. The primary objectives of the current study were to elucidate the mechanism(s) underlying the pro-colitic effects of dietary fructose and to determine whether this effect occurs in both microbially driven and genetic models of colitis. METHODS: Antibiotics and germ-free mice were used to determine the relevance of microbes for HFrD-induced worsening of colitis. Mucus thickness and quality were determined by histologic analyses. 16S rRNA profiling, in situ hybridization, metatranscriptomic analyses, and fecal metabolomics were used to determine microbial composition, spatial distribution, and metabolism. The significance of HFrD on pathogen and genetic-driven models of colitis was determined by using Citrobacter rodentium infection and Il10-/mice, respectively. RESULTS: Reducing or eliminating bacteria attenuated HFrDmediated worsening of DSS-induced colitis. HFrD feeding enhanced access of gut luminal microbes to the colonic mucosa

Diet is believed to be an important factor in the pathogenesis of Inflammatory Bowel Disease. High consumption of dietary fructose has been shown to exacerbate experimental colitis, an effect mediated through the gut microbiota. This study evaluated whether dietary alterations could attenuate the detrimental effects of a high fructose diet (HFrD) in experimental colitis. First, we determined whether the pro-colitic effects of a HFrD could be reversed by switching mice from a HFrD to a control diet. This diet change completely prevented HFrD-induced worsening of acute colitis, in association with a rapid normalization of the microbiota. Second, we tested the effects of dietary fiber, which demonstrated that psyllium was the most effective type of fiber for protecting against HFrD-induced worsening of acute colitis, compared to pectin, inulin or cellulose. In fact, supplemental psyllium nearly completely prevented the detrimental effects of the HFrD, an effect associated with a shift in the gut microbiota. We next determined whether the protective effects of these interventions could be extended to chronic colitis and colitis-associated tumorigenesis. Using the azoxymethane/dextran sodium sulfate model, we first demonstrated that HFrD feeding exacerbated chronic colitis and increased colitis-associated tumorigenesis. Using the same dietary changes tested in the acute colitis setting, we also showed that mice were protected from HFrD-mediated enhanced chronic colitis and tumorigenesis, upon either diet switching or psyllium supplementation. Taken together, these findings suggest that high consumption of fructose may enhance colon tumorigenesis associated with long-standing colitis, an effect that could be reduced by dietary alterations.

The most common histological classification of bile duct cancer is adenocarcinoma and squamous cell carcinoma (SCC) is relatively rare. We report a case of a 78-year-old man with SCC of the extrahepatic bile duct associated with metachronous para-aortic lymph node metastasis. He had undergone subtotal stomach-preserving pancreatoduodenectomy. The pathological findings demonstrated moderately differentiated SCC of the distal extrahepatic bile duct (T1N1M0, stage IIB). 6 months after surgery, recurrence of the para-aortic lymph node was shown in abdominal CT. 5 courses of tegafur/gimeracil/oteracil (S-1) plus cisplatin therapy was performed and the para-aortic lymph node disappeared, confirmed as complete response by imaging findings. The patient is alive without recurrence, 10 months after recurrence and chemotherapy.

The western diet has been suggested to contribute to the rising incidence of Inflammatory Bowel Diseases. This has led to the hypothesis that fructose, a component of the western diet, could play a role in the pathogenesis of Inflammatory Bowel Diseases. A high fructose diet is known to exacerbate experimental colitis. This study tested whether the expression of GLUT5, the fructose transporter, is a determinant of the severity of experimental colitis during elevated fructose consumption and whether ileal inflammation is associated with altered GLUT5 expression in Crohn's Disease. Studies in genetically engineered mice showed that in comparison to Glut5+/+ mice, feeding a 15 kcal% fructose diet to Glut5-/- mice led to worse dextran sodium sulfate (DSS)-induced colitis. This effect was associated with elevated levels of colonic fructose and a shift in the fecal microbiota in Glut5-/- mice. Importantly, treatment with broad-spectrum antibiotics protected against the worsening of colitis mediated by dietary fructose in Glut5-/- mice. Gene expression analysis revealed that GLUT5 levels are reduced in patients with Crohn's ileitis. Moreover, levels of GLUT5 negatively correlated with levels of pro-inflammatory mediators. Collectively, these results demonstrate that dietary constituent (fructose)-host gene (GLUT5) interactions can shape the colonic microbiota thereby impacting the severity of colitis.

We report a rare case of visceral injury after totally extraperitoneal endoscopic inguinal hernia repair. A 48-year-old man underwent needlescopic totally extraperitoneal repair of a direct inguinal hernia. Bleeding from a branch of the inferior epigastric vessels occurred at the beginning of the extraperitoneal dissection with a monopolar electrosurgical device. Hemostasis was prolonged. However, herniorrhaphy and mesh repair were successfully performed, and no peritoneal disruption or pneumoperitoneum was visible. The patient was discharged home on the next day. However, 30 h after this operation, he underwent diagnostic and operative laparoscopy because of acute abdominal pain. Ileal perforation was found and repaired, and pathological examination indicated cautery artifact. Thus, thermal damage to the ileum during the initial operation may have caused the bowel perforation. To the best of our knowledge, no other cases of bowel perforation after totally extraperitoneal repair without peritoneal disruption have been reported.