Decreased melatonin secretion is associated with increased intestinal permeability and marker of endotoxemia in alcoholics

• Published in: American journal of physiology: Gastrointestinal and liver physiology Vol. 308; no. 12; p. G1004
• Main Authors: Swanson, Garth R, Gorenz, Annika, Shaikh, Maliha, Desai, Vishal, Forsyth, Christopher, Fogg, Louis, Burgess, Helen J, Keshavarzian, Ali
• Format: Journal Article
• Language: English
• Published: United States 15-06-2015
• Subjects: Acute-Phase Proteins - metabolism; Adult; Aged; Aged, 80 and over; Carrier Proteins - metabolism; Cell Membrane Permeability - drug effects; Circadian Rhythm - physiology; Endotoxemia - etiology; Endotoxemia - metabolism; Female; Humans; Intestinal Absorption - drug effects; Intestinal Absorption - physiology; Intestines - metabolism; Liver Diseases, Alcoholic - complications; Male; Melatonin - metabolism; Membrane Glycoproteins - metabolism; Middle Aged; Sleep - physiology; alcohol; lipopolysaccharide-binding protein; lipopolysaccharide
• ISSN: 1522-1547
• DOI: 10.1152/ajpgi.00002.2015

Chronic heavy alcohol use is known to cause gut leakiness and alcoholic liver disease (ALD), but only 30% of heavy drinkers develop increased intestinal permeability and ALD. The hypothesis of this study was that disruption of circadian rhythms is a potential risk factor in actively drinking alcoholics for gut leakiness and endotoxemia. We studied 20 subjects with alcohol use disorder (AD) and 17 healthy controls (HC, 6 day workers, 11 night workers). Subjects wore a wrist actiwatch for 7 days and underwent a 24-h dim light phase assessment and urine collection for intestinal permeability. The AD group had significantly less total sleep time and increased fragmentation of sleep (P < 0.05). AD also had significantly lower plasma melatonin levels compared with the HC [mean area under the curve (AUC) 322.78 ± 228.21 vs. 568.75 ± 304.26 pg/ml, P = 0.03]. In the AD group, AUC of melatonin was inversely correlated with small bowel and colonic intestinal permeability (lactulose-to-mannitol ratio, r = -0.39, P = 0.03; urinary sucralose, r = -0.47, P = 0.01). Cosinor analysis of lipopolysaccharide-binding protein (marker of endotoxemia) and lipopolysaccharide every 4 h for 24 h in HC and AD subjects had a midline estimating statistic of rhythm of 5,026.15 ± 409.56 vs. 6,818.02 ± 628.78 ng/ml (P < 0.01) and 0.09 ± 0.03 vs. 0.15 ± 0.19 EU/ml (P < 0.05), respectively. We found plasma melatonin was significantly lower in the AD group, and lower melatonin levels correlated with increased intestinal permeability and a marker of endotoxemia. Our study suggests the suppression of melatonin in AD may promote gut leakiness and endotoxemia.