Biliary lactoferrin concentrations are increased in active inflammatory bowel disease: a factor in the pathogenesis of primary sclerosing cholangitis?

Abstract

1. One hypothesis for the link between inflammatory bowel disease and primary sclerosing cholangitis is that neutrophil activators, such as bacterial chemotactic peptides or neutrophil granule products themselves, pass from the inflamed colon to the liver via an enterohepatic circulation. However, there are no data on biliary concentrations of neutrophil granule products in patients with active and inactive inflammatory bowel disease.2. Gall bladder bile was obtained at laparotomy from 42 patients with ulcerative colitis and 21 patients with Crohn's disease. Biliary lactoferrin and myeloperoxidase concentrations were quantified by ELISA.3. In active ulcerative colitis, the mean lactoferrin concentration in gall bladder bile of 2.8+/-0.40 mg/l was higher than that seen after colectomy (1.2+/-0.11 mg/l; P<0.0001) or in patients with pouchitis (1.8+/-0.34 mg/l; P=0.06). In active Crohn's colitis, the mean lactoferrin concentration was 3.7+/-0.9 mg/l, compared with 1.1+/-0. 24 mg/l in the post-colectomy group (P<0.05) and 3.1+/-0.71 mg/l in those with active ileitis or ileocolitis. In contrast, biliary myeloperoxidase concentrations were low and comparable in all groups, with a mean concentration in the 42 patients with ulcerative colitis of 11.2+/-1.9 microgram/l.4. In contrast to myeloperoxidase, biliary lactoferrin concentrations are increased in active ulcerative colitis and Crohn's disease, and fall with colectomy and with disease remission. These findings indirectly support the hypothesis that bacterial chemotactic peptides (which induce selective degranulation of neutrophil secondary granules), and/or lactoferrin itself, undergo an enterohepatic circulation.

Targeting Gut Microbiota for the Treatment of Primary Biliary Cholangitis: From Bench to Bedside

“…The gut-liver axis was initially characterized in 1987 17 and was first reported to be implicated in liver pathogenesis in 1998. 18 The portal vein and the bile acid enterohepatic circulation establish bidirectional communication of the gut-liver axis, in which the liver directly receives gut-derived products. 14 , 19 In healthy conditions, the liver’s innate immune system is robust, allowing it to maintain immune tolerance against gut-derived antigens.…”

Cholestasis-Associated Pruritus and Its Pruritogens

“…Since cholestasis-associated pruritus is significantly improved by treatment with the antibiotic rifampicin (169), it seems plausible that gut microbiota are involved in cholestatic liver disease. The first link between gut microbiota and liver pathogenesis was made by Pereira et al, who hypothesized that neutrophil activators involved in inflammatory bowel disease, pass from the inflamed colon to the liver via the enterohepatic circulation (170). Biliary lactoferrin concentrations were increased in active ulcerative colitis and Crohn's disease, and fell with colectomy and disease remission.…”