Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis.

Commensal gut microflora and dietary fiber protect against colonic inflammation and colon cancer through unknown targets. Butyrate, a bacterial product from fermentation of dietary fiber in the colon, has been implicated in this process. GPR109A (encoded by Niacr1) is a receptor for butyrate in the colon. GPR109A is also a receptor for niacin, which is also produced by gut microbiota and suppresses intestinal inflammation. Here we showed that Gpr109a signaling promoted anti-inflammatory properties in colonic macrophages and dendritic cells and enabled them to induce differentiation of Treg cells and IL-10-producing T cells. Moreover, Gpr109a was essential for butyrate-mediated induction of IL-18 in colonic epithelium. Consequently, Niacr1(-/-) mice were susceptible to development of colonic inflammation and colon cancer. Niacin, a pharmacological Gpr109a agonist, suppressed colitis and colon cancer in a Gpr109a-dependent manner. Thus, Gpr10a has an essential role in mediating the beneficial effects of gut microbiota and dietary fiber in colon.

Branch-specific sialylation of IgG-Fc glycans by ST6Gal-I.

Sialylated forms of the Fc fragment of immunoglobulin G, produced by the human alpha2-6 sialyltransferase ST6Gal-I, were identified as potent anti-inflammatory mediators in a mouse model of rheumatoid arthritis and are potentially the active components in intravenous IgG anti-inflammatory therapies. The activities and specificities of hST6Gal-I are, however, poorly characterized. Here MS and NMR methodology demonstrates glycan modification occurs in a branch-specific manner with the alpha1-3Man branch of the complex, biantennary Fc glycan preferentially sialylated. Interestingly, this substrate preference is preserved when using a released glycan, suggesting that the apparent occlusion of glycan termini in Fc crystal structures does not dominate specificity.

The utility of early cross-sectional imaging to evaluate suspected acute mild pancreatitis.

BACKGROUND: There are roughly 300,000 hospitalizations for acute pancreatitis annually in the United States. Many of the affected patients at our institution undergo computed tomography (CT) or magnetic resonance imaging (MRI) unnecessarily early during their admissions. We hypothesize that cross-sectional imaging within 48 h of admission in patients meeting the criteria for acute, mild pancreatitis is over-utilized and does not change management. METHODS: We performed a retrospective analysis of patients with a discharge diagnosis of acute pancreatitis from our tertiary care institution from January 1, 2010 to December 31, 2015. Inclusion criteria were a lipase more than three times the upper limit of normal and clinical suspicion of pancreatitis. Exclusion criteria were an etiology of pancreatitis following endoscopic retrograde cholangiopancreatography, recurrent or chronic pancreatitis, severe pancreatitis, and ultrasound findings being the reason for imaging. RESULTS: Of the 166 patients who met the criteria for analysis, 105 (63.3%) underwent cross-sectional imaging within 48 h of presentation (CT: 104, MRI: 1). Of the examined CTs, 27 (26.0%) showed no abnormality and 55 (52.9%) revealed uncomplicated pancreatitis. The remaining 22 (21.2%) demonstrated at least one of the following: local complications, biliary ductal dilatation or other findings. On thorough chart review, only two patients received a beneficial change in management as a result of the early imaging. CONCLUSIONS: This analysis supports current guidelines that early cross-sectional abdominal imaging (CT or MRI) in patients with suspected acute mild pancreatitis does not alter medical management. Early imaging may lead to unnecessary resource use and patient irradiation.