Toxicological Centre, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium; Natural Products and Food - Research & Analysis (NatuRA), University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium.
Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium.
J Pharm Biomed Anal. 2022 Mar 20;211:114550. doi: 10.1016/j.jpba.2021.114550. Epub 2021 Dec 28.
Obesity is a major public health problem. Gut microbiome dysbiosis has been associated with obesity, however, little is known on the effect of the dysbiosis on the microbiotic bio-transformation of xenobiotics. Fecal samples of lean (n = 9) and obese (n = 4) female volunteers were collected and characterized by 16 S rDNA gene sequencing. The microbiotic biotransformation of chlorogenic acid was studied using the collected fecal samples of lean and obese subjects in the colon stage of the gastro-intestinal dialysis model with colon stage (GIDM-Colon). The concentration of anaerobic bacteria was lower for all obese samples in comparison to the samples of the lean volunteers. Differences in gut microbiome composition and bacterial concentration were observed between the two populations. The obese gut microbiome presented a lower metabolic activity in comparison to the lean population. Chlorogenic acid was completely biotransformed after 24 h colonic dialysis in the lean population while it was still present in the obese population. Furthermore, 23 and 13 biotransformation products were identified in the lean and obese population, respectively; 11 unique biotransformation products from the caffeic, feruoylquinic and quinic acid pathways were identified in the lean population. The results confirm that changes in gut microbiota related to obesity are associated with differences in microbiotic biotransformation of xenobiotics and thus possibly influencing the activity, bioavailability and toxicity of orally administered xenobiotics and drugs.
肥胖是一个主要的公共卫生问题。肠道微生物群落失调与肥胖有关，然而，对于这种失调对异源生物的微生物生物转化的影响知之甚少。收集了 9 名瘦（n=9）和 4 名肥胖（n=4）女性志愿者的粪便样本，并通过 16S rDNA 基因测序进行了表征。使用收集的瘦和肥胖志愿者的粪便样本，在肠道透析模型的结肠阶段（GIDM-Colon）中研究了绿原酸的微生物生物转化。与瘦志愿者的样本相比，所有肥胖样本的厌氧菌浓度都较低。两种人群的肠道微生物群落组成和细菌浓度存在差异。与瘦人群相比，肥胖人群的肠道微生物群代谢活性较低。绿原酸在 24 小时结肠透析后在瘦人群中完全转化，而在肥胖人群中仍存在。此外，在瘦和肥胖人群中分别鉴定出 23 和 13 种生物转化产物；在瘦人群中鉴定出了来自咖啡酸、阿魏酸和奎尼酸途径的 11 种独特的生物转化产物。研究结果证实，与肥胖相关的肠道微生物群变化与异源生物的微生物生物转化差异有关，从而可能影响口服异源生物和药物的活性、生物利用度和毒性。
