Gastroenterology 1990 Feb;98(2):414-23

Hepatic inflammation in rats with experimental small intestinal bacteria
overgrowth

Lichtman SN, Sartor RB, Keku J, Schwab JH
Department of Pediatrics, University of North Carolina, Chapel Hill

Abstract
Hepatobiliary inflammation and other extraintestinal manifestations accompany
certain intestinal disorders, perhaps because of proliferation or enhanced
transport of luminal bacteria or their phlogistic cell-wall components. Using
jejunal self-filling blind loops to create small bowel bacterial overgrowth, we
compared biochemical and histological evidence of hepatic inflammation in 3 rat
strains chosen for their variable inflammatory responses to bacterial cell wall
polymers. Lewis and Wistar rats developed weight loss, hepatomegaly, and hepatic
inflammation 4 and 12 wk, respectively, after creation of SFBL. Plasma aspartate
aminotransferase levels in Lewis rats 4 wk (578 +/- 77 U/L) and Wistar rats 12
wk (220 +/- 35 U/L) after self-filling blind loops were significantly greater
than in rats with self-emptying blind loops (112 +/- 24 U/L, p less than 0.001;
104 +/- 22, p less than 0.05) or sham-operated Lewis (84 +/- 24, p less than
0.001) or Wistar (78 +/- 10, p less than 0.001) rats. Randomized comparison
using a histology grading score showed abnormalities that paralleled
aminotransferase values. Lewis and Wistar rats with self-filling blind loops had
hepatic injury with bile duct proliferation, fibrosis and acute and chronic
periportal and focal parenchymal inflammation. Lewis and Wistar rats with
self-emptying blind loops developed occasional mild histologic lesions. 50% of
Lewis rats with self-filling blind loops for 4 wk died compared with only 15% in
other groups. However, Buffalo rats with self-filling blind loops developed no
weight loss, hepatomegaly, or hepatic injury. Anaerobic cultures of blood,
peritoneum and liver were negative in all strains. Diet-restricted,
sham-operated Wistar rats with weights similar to the Wistar rats with
self-filling blind loops did not develop histologic abnormalities or elevated
aminotransferase levels (76 +/- 31 U/L). These results show that experimental
small bowel bacterial overgrowth causes significant hepatic inflammation leading
to fibrosis in susceptible rat strains. Caloric deprivation and hepatic
bacterial invasion are not etiologically responsible. We suggest that bacterial
cell wall polymers or other bacterial toxins from the blind loop cause hepatic
lesions in genetically susceptible hosts