Abstract
Since hypobaric hypoxia significantly affects metabolic characteristics of intestinal flora, which plays an important role in the biotransformation of aspirin, high altitudes may influence the pharmacokinetics and therapeutic effects of aspirin in the intestines. In the present study, to test alterations of intestinal microbiota at high altitude comparing to that at low altitude, we analyzed rat feces from plain group and high-altitude group by 16S rRNA analysis. To detect concentrations of aspirin and salicylic acid, we established a reliable liquid chromatography tandem mass spectrometry method to measure aspirin and salicylic acid concentrations in fecal suspensions and plasma. Our study found that the plateau hypoxic environment caused a significant increase in Bacteroides in rat feces, while Corynebacterium, Prevotella, and Coprococcus were declined. In addition, compared with the plain group, the metabolic activity of fecal suspensions from the plateau group on aspirin was significantly reduced. More importantly, these changes in the intestinal microbiota led to increasing absorption of aspirin in the rats after rapidly ascent to the plateau, and a reduction in the pharmacodynamic index TXB2, which would possibly result in bleeding. In conclusion, our research provides new ideas for changes in plateau pharmacokinetics, and then guide the corresponding reduction in aspirin dose for the population quickly entering the plateau.
Highlights
The gut flora is the most momentous and diverse microbial community that functions symbiotically with humans and animals[1]
Most of aspirin is rapidly absorbed in Effects of intestinal flora on the pharmacokinetics and pharmacodynamics of aspirin the small intestine, in our current study, it has been proved that the intestinal flora plays a vital role in the metabolism of aspirin
We demonstrated that the metabolic activity of the plateau fecal suspensions on aspirin is significantly decreased compared with the plain group
Summary
The gut flora is the most momentous and diverse microbial community that functions symbiotically with humans and animals[1]. These complex populations of bacteria, viruses and fungi are crucial for maintaining inherent health, and in metabolizing exogenous xenobiotic[2]. It is worth mentioning that the ability of the intestinal flora to metabolize drugs is efficient but has often been underestimated in the past[3]. The gut microbiota is not static, but rather is highly variable. Any alteration or dysbiosis of the gut microbiota could directly or indirectly influence microbe-mediated bioactivation of the drug[4].
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