Is a leaky gut involved in the pathogenesis of intrahepatic cholestasis of pregnancy?
Increased gastrointestinal permeability has been demonstrated in several liver diseases. It may facilitate the absorption of gut-derived endotoxin-stimulating Kupffer cells to release proinflammatory cytokines or other potentially hepatotoxic compounds. We examined gastrointestinal permeability, plasma levels of anti-lipopolysacharides (anti-LPS), and four proinflammatory cytokines in 20 patients with intrahepatic cholestasis of pregnancy (ICP) compared with 22 normal pregnant and 29 non-pregnant women. Urinary excretion of sucrose and the urinary lactulose/mannitol (L/M) ratio after a standard oral load were used to assess gastrointestinal permeability. Anti-LPS (IgA, IgM, and IgG) were measured in peripheral blood by Human EndoCAb test kit; TNF-alpha, IL-1beta, IL-6, and IL-10 by Quantikine HS human immunoassays. Sucrose urinary excretion was similar in the three groups, indicating normal gastric permeability. The urinary L/M ratio was significantly higher in ICP than in the other groups [median (interquartile range): 0.018% (0.011-0.023) in ICP, 0.012% (0.009-0.016) in normal pregnancies, and 0.009% (0.008-0.012) in non-pregnant women, P < .01]. No significant differences were found in anti-LPS or cytokines plasma levels except slightly higher levels of IL-6 in ICP patients than in non-pregnant women (P < .05). Four of five women with abnormal urinary L/M ratio during ICP continued to show abnormalities in tests up to 2 years after delivery. In conclusion, an increased intestinal permeability was detected in ICP patients during and after pregnancy. A "leaky gut" may participate in the pathogenesis of ICP by enhancing the absorption of bacterial endotoxin and the enterohepatic circulation of cholestatic metabolites of sex hormones and bile salts.
Departamento de Medicina Oriente, Facultad de Medicina, Universidad de Chile, Santiago de Chile. hreyes@med.uchile.cl
Humberto
H
Reyes
Rodrigo
R
Zapata
Ismael
I
Hernández
Martín
M
Gotteland
Lorena
L
Sandoval
María Isabel
MI
Jirón
Joaquín
J
Palma
Ramón
R
Almuna
Juan Jorge
JJ
Silva
D000328:Adult; D000906:Antibodies / Q000097:blood; D016022:Case-Control Studies; D002780:Cholestasis, Intrahepatic / Q000097:blood / Q000209:etiology* / Q000276:immunology / Q000652:urine; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D007413:Intestinal Mucosa / Q000378:metabolism*; D007792:Lactulose / Q000652:urine; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008353:Mannitol / Q000652:urine; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D010539:Permeability; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood / Q000209:etiology* / Q000276:immunology / Q000652:urine; D011256:Pregnancy Outcome
D000906:Antibodies; D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008353:Mannitol; D007792:Lactulose