Chyme Reinfusion Restores the Regulatory Bile Salt-FGF19 Axis in Patients With Intestinal Failure.

BACKGROUND AND AIMS: Automated chyme reinfusion (CR) in patients with intestinal failure (IF) and a temporary double enterostomy (TDE) restores intestinal function and protects against liver injury, but the mechanisms are incompletely understood. The aim was to investigate whether the beneficial effects of CR relate to functional recovery of enterohepatic signaling through the bile salt-FGF19 axis. APPROACH AND RESULTS: Blood samples were collected from 12 patients, 3 days before, at start, and 1, 3, 5, and 7 weeks after CR initiation. Plasma FGF19, total bile salts (TBS), 7-α-hydroxy-4-cholesten-3-one (C4; a marker of bile salt synthesis), citrulline (CIT), bile salt composition, liver tests, and nutritional risk indices were determined. Paired small bowel biopsies prior to CR and after 21 days were taken, and genes related to bile salt homeostasis and enterocyte function were assessed. CR induced an increase in plasma FGF19 and decreased C4 levels, indicating restored regulation of bile salt synthesis through endocrine FGF19 action. TBS remained unaltered during CR. Intestinal farnesoid X receptor was up-regulated after 21 days of CR. Secondary and deconjugated bile salt fractions were increased after CR, reflecting restored microbial metabolism of host bile salts. Furthermore, CIT and albumin levels gradually rose after CR, while abnormal serum liver tests normalized after CR, indicating restored intestinal function, improved nutritional status, and amelioration of liver injury. CR increased gene transcripts related to enterocyte number, carbohydrate handling, and bile salt homeostasis. Finally, the reciprocal FGF19/C4 response after 7 days predicted the plasma CIT time course. CONCLUSIONS: CR in patients with IF-TDE restored bile salt-FGF19 signaling and improved gut-liver function. Beneficial effects of CR are partly mediated by recovery of the bile salt-FGF19 axis and subsequent homeostatic regulation of bile salt synthesis.

Dietary pattern, a modifiable risk factor that can be easily assessed for atherosclerosis vascular disease prevention in clinical practice.

OBJECTIVES: Nutrition is one of the modifiable risk factors of atherosclerosis vascular diseases (VD). We aimed to (i) evaluate the dietary patterns associated with VD in clinical practice using a validated FFQ; and (ii) determine potential independent sociodemographic and behavioural factors that are involved in such dietary patterns. The FFQ determined the vascular dietary score (VDS; ranges from -17 to 19) for each subject. DESIGN: Cross-sectional study. SETTING: A general practitioner's (GP) office in 2009. SUBJECTS: A total of 250 French subjects (18-84 years old). RESULTS: A total of 21 % had a favourable vascular diet (VDS ≥ 8), 79 % needed to improve their diet (VDS < 8) and 21 % had a risky vascular diet (VDS ≤ -1). A step-by-step multivariate linear regression analysis with stepwise selection was performed using the VDS as a dependent variable. Significant variables were: age (ß = 0·495, P < 0·0001), men (ß = -0·282, P < 0·0001), 'sport ≥ 1 h/week' (ß = 0·253, P = 0·001), 'walking 20 min/d' (ß = 0·161, P = 0·012), 'former smoker' (ß = 0·118, P = 0·029), previous nutritional advice (ß = 0·105, P = 0·049), 'alcohol ≥ 20 g/d' (ß = -0·216, P < 0·0001) and 'primary school' (ß = -0·156, P = 0·010). The R2 coefficient of this model was 0·347 (P < 0·0001). In all, 88·7 % of the subjects found the evaluation very interesting and 89·6 % believed that the GP should perform it. CONCLUSIONS: Simple dietary assessment for VD prevention can be easily performed in clinical practice to allow physicians to give objective and rapid advice for each patient. Age, educational status, alcohol consumption, gender and physical activity are associated with the VDS. Compliance with such evaluation was found to be very high, which should encourage larger dietary screening in the population in order to reduce the impact of VD.