Nordyke, Cynthia K.

Background: Primary sclerosing cholangitis (PSC) is a major risk factor for cholangiocarcinoma (CCA). We investigated biliary and fecal microbiota to determine whether specific microbes in the bile or stool are associated with PSC or CCA. Methods: Bile was obtained from 32 patients with PSC, 23 with CCA with PSC, 26 with CCA without PSC, and 17 controls. Over 90% of bile samples were from patients with perihilar CCA. Stool was obtained from 31 patients with PSC (11 were matched to bile), 16 with CCA with PSC (10 matched to bile), and 11 with CCA without PSC (6 matched to bile). Microbiota composition was assessed using 16SrRNA-marker-based sequencing and was compared between groups. Results: Bile has a unique microbiota distinguished from negative DNA controls and stool. Increased species richness and abundance of Fusobacteria correlated with duration of PSC and characterized the biliary microbiota in CCA. Stool microbiota composition showed no significant differences between groups. Conclusions: We identified a unique microbial signature in the bile of patients with increased duration of PSC or with CCA, suggesting a role for microbiota-driven inflammation in the pathogenesis and or progression to perihilar CCA. Further studies are needed to test this hypothesis.

Low-compliance perfusion manometry and clinical outcome were used to assess the chronic effects of feeding on functional maturation of the preterm intestine in 32 infants. During the first postnatal week, 16 infants received a small volume of formula to supplement their routine parenteral nutrition (24 ml.kg-1.day-1), and 16 received an equal volume of water. After 10 days of enteral "feedings," the manometric tracings of those infants who had received nutrient feedings had more migrating activity (P < 0.01) and less clustered phasic activity (P < 0.05) during fasting than did the tracings of those infants who had received nonnutrient feedings containing sterile water. Infants who received nutrient feedings demonstrated a change in motor activity in response to feeding; infants who had received water feedings failed to show a change in motor activity in response to feeding. After water-fed infants were given formula feedings for 2 wk, their motor activity patterns were similar to those who had initially been fed formula, and their motor responses to feeding were restored. Despite normalization of their motor activity patterns by 1 mo of age, these water-fed infants established full enteral nutrition and full nipple feedings later than did infants who had been fed formula (P < 0.01), suggesting that the delay of enteral feedings in preterm infants does not permit optimal intestinal maturation of nonmucosal functions.