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Hepatic inflammation in rats with experimental small intestinal bacterial overgrowth
S N Lichtman1, R B Sartor, J Keku
1Department 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.
Insights
Small bowel bacterial overgrowth causes liver inflammation and fibrosis in susceptible rats. Bacterial toxins, not bacterial invasion or diet, trigger these hepatic lesions, highlighting genetic susceptibility.
Area of Science:
- Gastroenterology
- Hepatology
- Microbiology
Background:
- Intestinal disorders can lead to hepatobiliary inflammation and extraintestinal issues.
- This may be due to increased bacterial proliferation or transport of bacterial components.
Purpose of the Study:
- To investigate if small bowel bacterial overgrowth causes hepatic inflammation.
- To compare biochemical and histological liver inflammation in rat strains with varying responses to bacterial cell wall polymers.
Main Methods:
- Created jejunal self-filling blind loops (SFBL) to induce small bowel bacterial overgrowth in Lewis, Wistar, and Buffalo rats.
- Compared biochemical (plasma aspartate aminotransferase) and histological liver damage markers between SFBL, self-emptying blind loop, and sham-operated rats.
- Performed anaerobic cultures of blood, peritoneum, and liver; assessed diet-restricted controls.
Main Results:
- Lewis and Wistar rats with SFBL showed significant weight loss, hepatomegaly, and hepatic inflammation (bile duct proliferation, fibrosis, inflammation) at 4 and 12 weeks, respectively.
- Elevated plasma aspartate aminotransferase levels and histological abnormalities paralleled SFBL in susceptible strains.
- Buffalo rats with SFBL showed no adverse effects; diet restriction did not cause liver damage, and cultures were negative, ruling out caloric deprivation and bacterial invasion.
Conclusions:
- Experimental small bowel bacterial overgrowth induces significant hepatic inflammation and fibrosis in genetically susceptible rat strains.
- Bacterial cell wall components or toxins from the blind loop are implicated, not caloric deprivation or hepatic bacterial invasion.
- Highlights the role of genetic predisposition in developing liver injury from bacterial overgrowth.
