The microbiome can predict mucosal healing in small intestine in patients with Crohn's disease.

BACKGROUND: Mucosal healing is the main treatment goal for Crohn's disease. In this situation, some patients have difficulty with endoscopic evaluation of the entire small intestine. Crohn's disease is closely associated with the gut microbiota, but the relationship between the microbiome and disease activity in the small intestine remains unclear. We examined the association between the microbiome and endoscopic findings in the small intestine and determined whether the microbiome can predict mucosal healing. METHODS: The patients with Crohn's disease who were scheduled for capsule or balloon-assisted endoscopy were included in this prospective study. Patients whose entire small intestine was evaluated were divided into two groups based on ulcerative findings. The microbiomes in the fecal samples were analyzed using 16S rRNA sequencing. RESULTS: The 38 enrolled patients were divided into the ulcer group (24) and mucosal healing group (14). The ulcer group exhibited lower α diversity. Six genera, namely Faecalibacterium (P = 0.008), Lachnospira (P = 0.009), Paraprevotella (P = 0.01), Dialister (P = 0.012), Streptococcus (P = 0.025), and Clostridium (P = 0.028) were enriched in the mucosal healing group. A predictive score for mucosal healing was defined using these six genera. The area under the curve was 0.795 and the sensitivity and specificity for predicting mucosal healing were 0.643 and 0.917, respectively. CONCLUSIONS: Fecal microbiome is corelated with disease activity in the entire small intestine in Crohn's disease patients. The predictive score proposed by microbiota characteristics was a potential biomarker for mucosal healing in the small intestine.

Microbiota profile is different for early and invasive colorectal cancer and is consistent throughout the colon.

BACKGROUND AND AIM: Microbiota have been associated with several diseases including colorectal cancer (CRC). This study aimed to evaluate the microbiota in early/invasive CRC utilizing stool and cytological brushes to determine differences in relative abundance (RA). METHODS: Colonoscopy patients referred for endoscopic submucosal dissection or previous to CRC surgery were prospectively enrolled. Stool was collected pre-bowel preparation; and brush samples were taken during colonoscopy (three regions). DNA extraction, 16S rRNA next generation sequencing, and biostatistics (qiime and stamp software packages) followed. Primary outcome was the difference in RA of the Fusobacterium genus between the groups. Secondary outcomes included analyses of other microbiota. RESULTS: Twenty-five patients were included, of which 14 had invasive cancer (≥ 1000 mm into the submucosa). The three major genera for invasive cancer were Bacterioides, Oribacterium, and Fusobacterium, whereas for early cancer were Oribacterium, Bacterioides, and Prevotella (decreasing order of RA). There was a significantly higher RA of Fusobacterium in the invasive cancer group (9.65% vs 0.95%, respectively, P < 0.001). The RA of all genera was similar throughout the colon. In addition to Fusobacterium, the genera Corynebacterium, Enterococcus, Neisseria, Porphyromonas, and Sclegelella showed statistically higher RA in the invasive cancer group. Conversely, the genera Oribacterium, Desulfovibrio, Clostridiales, and Lactobacillus showed lower RA in the invasive cancer group. CONCLUSIONS: The RA of Fusobacterium is higher with invasive CRC than in early CRC patients. In addition, five other bacteria genera were found to be increased, and four decreased in invasive CRC patients. The microbiota per patient was similar throughout the colon.

A case of mucinous cystic neoplasm of the pancreas misdiagnosed as a pancreatic pseudocyst at the initial exam and resected after a 2-year follow-up.

A 44-year-old woman was referred to our hospital because of a cystic lesion in the pancreatic body that was found by computed tomography (CT) as a result of a screening for impaired liver function after the patient presented with a high fever in 2011. Trans-abdominal ultrasonography (US) revealed a 33-mm unilocular cyst within the pancreatic body and a 5-mm hypoechoic mass in the pancreatic neck. Contrast-enhanced CT showed a slight enhancement around the cyst and a mild dilation of the main pancreatic duct, but neither septum nor nodule was detected inside. Contrast-enhanced endoscopic ultrasonography (CE-EUS) revealed a hyperechoic elevated lesion inside the cystic lesion without enhancement in the pancreatic body; CE-EUS also revealed a 5-mm homogeneous hypoechoic mass with a remarkable enhancement in the pancreatic neck with the use of Sonazoid(®) as a contrast medium. These lesions were diagnosed as a pancreatic pseudocyst and a neuroendocrine tumor (NET), respectively, and were followed up with periodic examinations. The cystic lesion showed contraction 6 months after the initial exam. However, US revealed an enlargement of the cystic lesion to 40 mm in diameter 2 years after the initial exam, and EUS showed irregular thickening of the wall with a cyst-in-cyst appearance. The diagnoses of a mucinous cystic neoplasm (MCN) and a concomitant small NET were made after a distal pancreatectomy. We herein report a rare case of MCN that showed various morphological changes over 2 years of observation.

[A case of type 2 autoimmune pancreatitis associated with Crohn disease].

A 45-year-old woman visited our hospital due to upper left quadrant pain and melena. Colonoscopy revealed longitudinal ulcers in the transverse colon. The endoscopic findings and pathological examination of a biopsy specimen led to diagnosis of Crohn disease, and mesalazine was administered. Although the colorectal lesions showed improvement with mesalazine, a blood test revealed elevation of biliary enzymes. Endoscopic retrograde cholangiopancreatography showed diffuse narrowing of the main pancreatic duct and smooth stricture of the distal bile duct. Steroid therapy improved the pancreatic lesion, which was diagnosed as type 2 autoimmune pancreatitis.

Protective role of Gipie, a Girdin family protein, in endoplasmic reticulum stress responses in endothelial cells.

Continued exposure of endothelial cells to mechanical/shear stress elicits the unfolded protein response (UPR), which enhances intracellular homeostasis and protect cells against the accumulation of improperly folded proteins. Cells commit to apoptosis when subjected to continuous and high endoplasmic reticulum (ER) stress unless homeostasis is maintained. It is unknown how endothelial cells differentially regulate the UPR. Here we show that a novel Girdin family protein, Gipie (78 kDa glucose-regulated protein [GRP78]-interacting protein induced by ER stress), is expressed in endothelial cells, where it interacts with GRP78, a master regulator of the UPR. Gipie stabilizes the interaction between GRP78 and the ER stress sensor inositol-requiring protein 1 (IRE1) at the ER, leading to the attenuation of IRE1-induced c-Jun N-terminal kinase (JNK) activation. Gipie expression is induced upon ER stress and suppresses the IRE1-JNK pathway and ER stress-induced apoptosis. Furthermore we found that Gipie expression is up-regulated in the neointima of carotid arteries after balloon injury in a rat model that is known to result in the induction of the UPR. Thus our data indicate that Gipie/GRP78 interaction controls the IRE1-JNK signaling pathway. That interaction appears to protect endothelial cells against ER stress-induced apoptosis in pathological contexts such as atherosclerosis and vascular endothelial dysfunction.