Colonic fermentation as affected by antibiotics and acidic pH: Application of an in vitro model

Summary: Antimicrobial substances such as vancomycin or metronidazole suppress normal gut flora, thereby preventing physiological fermentation of colonic substrates that may promote mucosal inflammation. This study was designed to establish an in vitro model of microbial metabolism in the colon under control and disturbed conditions (acidic pH) to investigate specific effects of vancomycin and metronidazole on the production of short chain fatty acids (SCFA), which play a pivotal role in maintaining homeostasis in the colon. The experiments were carried out with the colon simulation technique (Cositec) representing an in vitro model for the semi-continuous incubation of defined colon contents. Inocula and fermentable substrates were sampled from cecal contents of fistulated pigs. Disturbed microbial metabolism was generated by reduction of pH in the fermentation vessels from 6.7 to 5.8 and 5.1. In general, application of either vancomycin or metronidazole resulted in a significant decrease of SCFA production rates indicating substantial disturbance of the homeostasis of microbial metabolism. With low doses of vancomycin acetate and butyrate production rates were reduced and with high doses of the antibiotic propionate production was inhibited to a greater extent. Treatment with metronidazole inhibited butyrate production almost completely. Similarly, low pH caused a reduction in total SCFA production, which was mainly due to respective decrease of acetate synthesis. Metronidazole effects were not consistently changed at low pH. The Cositec system provides an excellent facility to test the effects of different antibiotics under defined conditions. In this study, both vancomycin and metronidazole affected microbial metabolism to a considerable extent. Both substances may thus be responsible for disturbances of colon function in vivo.

Beeinflussung des mikrobiellen Dickdarmstoffwechsels durch Antibiotika und sauren pH-Wert: Untersuchung in einem In-vitro-Modell

Mithilfe der Kolon-Simulationstechnik (Cositec), einer semikontinuierlichen In-vitro-Inkubationsmethode, wurden die Auswirkungen des Antibiotikums Vancomycin und des Chemotherapeutikums Metronidazol auf den Stoffwechsel der Dickdarmflora des Schweines untersucht. Als Spendertiere für die Inokula und fermentierbaren Substrate dienten Mastschweine, die mit einer Zökumkanüle versehen waren. Des Weiteren wurde ein Modell zur Störung des mikrobiellen Stoffwechsels im Cositec-System ohne Zusatz von Antibiotika etabliert. Dazu wurde der pH-Wert im Cositec-System von pH 6,7 auf 5,8 bzw. 5,1 erniedrigt. Schließlich wurde die gleichzeitige Wirkung von saurem pH und Metronidazol auf den Dickdarmstoffwechsel geprüft. Beide antimikrobiellen Wirkstoffe verursachten eine signifikante Störung des mikrobiellen Stoffwechsels, die sich vor allem in einer Abnahme der Produktion kurzkettiger Fettsäuren (SCFA) manifestierte. Bei niedrigen Vancomycin-Konzentrationen waren die Produktionsraten von Acetat und Butyrat erniedrigt, während die Propionat-Produktionsrate bei höheren Dosen vermindert war. Bei Metronidazol-Gabe war die Butyratbildung fast vollständig unterbunden. In ähnlicher Weise wurde die SCFA-Produktion durch die alleinige pH-Absenkung vermindert, wobei dies insbesondere mit einer Hemmung der Azetatbildung einherging. Bei saurem pH war der Metronidazol-Effekt nicht wesentlich verändert. Das Cositec-System stellt eine gut geeignete Technik zur Untersuchung von Antibiotikaeffekten auf den Dickdarmstoffwechsel unter definierten Bedingungen dar. Die Ergebnisse zeigen, dass Vancomycin und Metronidazol den mikrobiellen Dickdarmstoffwechsel in erheblichem Maße beeinträchtigen. Eine Übertragung dieser In-vitro-Ergebnisse auf In-vivo-Verhältnisse könnte zu einem größeren Verständnis der unter Vancomycin- und Metronidazol-Anwendung beobachteten Störungen der Dickdarmfunktion beitragen.

Key words

Vancomycin - Metronidazole - Colon - Colon Simulation Technique - Short Chain Fatty Acids

Schlüsselwörter

Vancomycin - Metronidazol - Kolon - Cositec - kurzkettige Fettsäuren

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