Role of intestinal bacterial overgrowth in ethanol production and metabolism in rats

doi:10.1016/0016-5085(86)90081-8

Gastroenterology

Volume 90, Issue 1, January 1986, Pages 103-110

https://doi.org/10.1016/0016-5085(86)90081-8 Get rights and content

Abstract

To investigate the role of intestinal bacterial overgrowth on the production and metabolism of ethanol, rats with a jejunal self-filling diverticulum (blind-loop) were compared to controls with a selfemptying diverticulum. Both endogenous ethanol and acetaldehyde were found in the blind-loop contents. Intragastric administration of sucrose produced a marked increase in acetaldehyde and acetate in the portal venous blood, with only a modest elevation of ethanol. Blind-loop contents readily oxidized ethanol to acetaldehyde in a concentration-dependent manner and more actively under aerobic than anaerobic conditions. This oxidation was inhibited by antibiotics and was reproduced with isolated microorganisms. Intragastric administration of ethanol to rats With blind-loops markedly increased acetaldehyde and acetate concentrations in the portal vein and, to a lesser extent, in the systemic blood, compared with the controls. By contrast, both portal and systemic blood ethanol concentrations were lower in the rats with a blindloop compared with controls, even though the amounts of ethanol retained in the digestive tract were similar. A dose of ethanol about twice as large as in controls was required to produce similar systemic blood levels. Both in rats with a blind-loop and in the controls, the areas under the curve of blood ethanol concentrations were smaller after intragastric than after intravenous ethanol administration (1 g ethanol/kg body wt). This difference was exaggerated in the rats with a blind-loop. Thus, a considerable amount of ethanol is oxidized in the gastrointestinal lumen of rats with a blind-loop. The resulting high concentrations of acetaldehyde, both in the intestinal lumen and the portal blood, may have deleterious effects on the gastrointestinal mucosa and the liver.

References (24)

CE King et al.
Small intestinal bacterial overgrowth
Gastroenterology
(1979)
WS Ruddell et al.
Effect of cimetidine on the gastric bacterial flora
Lancet
(1980)
E Mezey et al.
Endogenous ethanol production and hepatic disease following jejunoileal bypass for morbid obesity
Am J Clin Nutr
(1975)
RM Donaldson et al.
Malabsorption of Co⁶⁰-labeled cyanocobalamin in rats with intestinal diverticula. II. Studies on contents of the diverticula
Gastroenterology
(1962)
RW Guynn et al.
Enzymatic determination of acetate
RW Guynn et al.
Direct enzymic determination of acetate in tissue extracts in the presence of labile acetate esters
Anal Biochem
(1974)
RJK Julkunen et al.
First pass metabolism of ethanol: an important determinant of blood levels after alcohol consumption
Alcohol
(1985)
RJK Julkunen et al.
First pass metabolism of ethanol: a gastrointestinal barrier against the systemic toxicity of ethanol
Life Sci
(1985)
RL Peters et al.
Post-jejunoileal-bypass hepatic disease. Its similarity to alcoholic hepatic disease
Am J Clin Pathol
(1975)
JC Bode et al.
The effect of cimetidine treatment on ethanol formation in human stomach
Scand J Gastroenterol
(1984)

FA Klipstein et al.

Enterotoxigenic intestinal bacteria in tropical sprue

Ann Intern Med

(1973)

HA Krebs et al.

The physiological role of liver alcohol dehydrogenase

Biochem J

(1970)

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Citation Excerpt :
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: This research was supported by the Veterans Administration and by grant No. AA 03508 from the Department of Health and Human Services.

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Role of intestinal bacterial overgrowth in ethanol production and metabolism in rats

Abstract

Gastroenterology

Lancet

Am J Clin Nutr

Gastroenterology

Anal Biochem

Alcohol

Life Sci

Post-jejunoileal-bypass hepatic disease. Its similarity to alcoholic hepatic disease

Am J Clin Pathol

The effect of cimetidine treatment on ethanol formation in human stomach

Scand J Gastroenterol

Enterotoxigenic intestinal bacteria in tropical sprue

Ann Intern Med

The physiological role of liver alcohol dehydrogenase

Biochem J