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Evidence for peptidoglycan absorption in rats with experimental small bowel bacterial overgrowth
S N Lichtman1, J Keku, J H Schwab
1Department of Pediatrics, University of North Carolina, Chapel Hill 27599-7220.
Abstract:
Surgical creation of jejunal self-filling blind loops (SFBL) causes small bowel bacterial overgrowth which is associated with hepatobiliary inflammation in the susceptible Lewis and Wistar rat strains. Since hepatic injury occurs when small bowel anaerobic bacterial concentrations are increased 4 to 6 log10 units per ml and hepatic bacterial cultures are negative, we postulate that the inflammation is caused by absorption of phlogistic cell wall polymers originating from bacteria within the loop. To demonstrate absorption of bacterial cell wall polymers, we measured plasma and hepatic levels of immunoreactive peptidoglycan-polysaccharide (PG-PS) following intraluminal injection as well as anti-PG antibodies as an indirect measure of absorption and/or accumulation of endogenous PG. PG-PS purified from group A streptococci was detected in plasma by enzyme-linked immunosorbent assay after intraluminal injection; rats with SFBL showed significantly more uptake into plasma and the liver than sham-operated rats or SFBL rats which were treated with metronidazole (P less than 0.025). Total plasma immunoglobulin A (IgA), IgG, and IgM levels did not differ among sham-operated rats and those with self-emptying blind loops or SFBL, but plasma anti-PG IgA (P less than 0.05), IgG, and IgM (P less than 0.01) levels were increased in rats with SFBL. Metronidazole and tetracycline prevented the elevation of anti-PG antibody, but gentamicin and polymyxin B did not. Anti-lipid A, anti-soy protein, and anti-chow antibodies in plasma were not consistently increased in rats with SFBL indicating the lack of a generalized antibody response to luminal antigens. These data suggest that PG from normal flora bacteria is absorbed from the intestinal lumen and that mucosal injury and/or increased luminal concentrations of PG, such as those induced by small bowel bacterial overgrowth, lead to enhanced absorption of potentially inflammatory bacterial polymers.
Insights
Bacterial cell wall polymers from small intestinal bacterial overgrowth are absorbed and cause liver inflammation. Antibiotics like metronidazole prevent this inflammatory response by reducing bacterial overgrowth.
Area of Science:
- Gastroenterology
- Immunology
- Hepatology
Background:
- Surgical creation of jejunal self-filling blind loops (SFBL) in rats leads to bacterial overgrowth.
- This overgrowth is associated with hepatobiliary inflammation, even with negative hepatic bacterial cultures.
Purpose of the Study:
- To investigate the hypothesis that absorbed bacterial cell wall polymers cause inflammation in SFBL rats.
- To measure plasma and hepatic levels of peptidoglycan-polysaccharide (PG-PS) and anti-PG antibodies.
Main Methods:
- Intraluminal injection of PG-PS from group A streptococci.
- Enzyme-linked immunosorbent assay (ELISA) to detect PG-PS in plasma and liver.
- Measurement of plasma immunoglobulin A (IgA), IgG, IgM, and anti-PG antibodies.
- Treatment with antibiotics (metronidazole, tetracycline, gentamicin, polymyxin B).
Main Results:
- PG-PS was detected in plasma and liver of SFBL rats, with significantly higher levels compared to controls.
- SFBL rats showed increased plasma anti-PG IgA, IgG, and IgM levels.
- Metronidazole and tetracycline prevented the rise in anti-PG antibodies, while other antibiotics did not.
- No generalized antibody response to other luminal antigens was observed.
Conclusions:
- Bacterial peptidoglycan from normal flora is absorbed from the gut lumen.
- Increased luminal concentrations of PG, due to small intestinal bacterial overgrowth, enhance the absorption of these potentially inflammatory bacterial polymers.
- This absorption contributes to mucosal injury and hepatobiliary inflammation.