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At least 37 records · Page 2Linked to original sources
PubMed1997

Metabolism of azetirelin, a new thyrotropin-releasing hormone (TRH) analogue, by intestinal microorganisms.

PURPOSE: We evaluated the effect of luminal bacterial metabolism on intestinal absorption of azetirelin in rats. In vitro characteristics of bacterial metabolism of azetirelin were also investigated with the goal of overcoming the low stability of the peptidic drug against luminal microorganisms. METHODS: Plasma azetirelin levels after oral administration to antibiotic-pretreated rats was examined. In vitro incubation experiments with bacterial suspensions were also performed to clarify the location of azetirelin breakdown activity as well as the effects of oxygen, pH, and various protease inhibitors on drug metabolism. RESULTS: Plasma azetirelin levels were sustained after oral administration to antibiotic-treated rats. Incubation with rat luminal contents demonstrated that azetirelin was metabolized by anacrobic bacteria, which are predominant in the distal intestine. Fecal suspensions from rats, dogs, and humans showed comparable metabolic activity. Azetirelin breakdown in the bacterial suspension was pH-dependent and was inhibited in the presence of bacitracin or puromycin. CONCLUSIONS: Bacterial metabolism influences the degree of absorption of azetirelin in the distal intestine. Control of the luminal pH environment may be a practical method for improving the stability of azetirelin against intestinal microorganisms.

Animals↗
PubMed2000

Linoleic acid conjugation by human intestinal microorganisms is inhibited by glucose and other substrates in vitro and in gnotobiotic rats.

The anticarcinogen conjugated linoleic acid (CLA) is a product of bacterial activity that isomerizes linoleic acid (LA) in the rumen of herbivores. Therefore, fatty dairy products in the human diet are enriched with CLA. Although bacteria capable of in vitro LA conjugation were detected in the human intestinal tract, CLA synthesis from dietary sunflower seed oil was not observed in gnotobiotic rats associated with these intestinal bacteria. The objective of the study was to investigate variables that affect LA conjugation. In vitro, LA conjugation was strongly inhibited by glucose and other substrates. Concentrations of 1.5 mmol glucose/L inhibited LA conjugation by 50%. Methyl-alpha-D-glucoside was a less effective inhibitor than glucose, and 2-deoxy-D-glucose did not inhibit LA conjugation at all. To analyze the concentration of carbohydrates in intestinal contents, the LA-conjugating bacterial mixed culture and human fecal microorganisms were introduced into germ-free rats. Samples of feces and cecum and colon contents of both groups exhibited in vitro LA-conjugating activity. Rats associated with human intestinal microorganisms contained 5.7 +/- 1. 3 mmol glucose/L in the cecal contents and 6.6 +/- 1.0 mmol glucose/L in the colonic contents. Rats associated with CLA-producing bacterial culture contained 3.4 +/- 1.3 mmol glucose/L in the cecal contents and 4.2 +/- 1.0 mmol glucose/L in the colonic contents. These values are within a range that may explain the observed inhibition of LA conjugation in vivo.

Animals↗
PubMed1980

Heterotrophic nitrification by intestinal microorganisms.

From studies of nitrate balance in man and analyses of fecal and ileostomy samples, the possibility that nitrite and nitrate are formed de novo in the intestine, possibly by heterotrophic nitrification has emerged. This proposition significantly alters our previous conceptions of man's exposure to nitrite and suggests that nitrite may play a role in the cause of intestinal cancer. Heterotrophic nitrification has been demonstrated in various microorganisms. Our work has shown that intestinal heterotrophic microbial isolates from man are able to oxidize nitrogenous compounds to nitrite. These isolates include both procaryotes and eucaryotes.

Actinomyces↗
PubMed1981

Evaluation of nitrate synthesis by intestinal microorganisms in vivo.

The nitrate balance of germfree and conventional rats was assessed to determine whether the intestinal flora produces nitrate in vivo. The results indicate that there can be excess nitrate in the urine of germfree as well as conventional rats. This nitrate is apparently of host origin, and the presence of intestinal flora decreases the output of nitrate in urine.

Animals↗
PubMed1993

Steroid metabolism with intestinal microorganisms.

As a result of the metabolic activities of numerous anaerobic microorganisms with sterols, bile acids and steroid hormones as substrates in connection with the enterohepatic circulation of these compounds, the intestine may be considered as an "endocrine" active site or organ. The review summarizes transformations of steroids by anaerobic intestinal bacteria, the physiological and supposed pathophysiological meaning thereof. The aim is to recommend further investigation in this field with respect to both the elucidation of the reactions and biological responses.

Animals↗