吲哚和对甲酚是最重要的尿毒症毒素的前体,通过肠道细菌的蛋白水解群落从氨基酸色氨酸和酪氨酸的发酵产生。本研究侧重于微生物组组成之间的关系,吲哚和对甲酚的粪便水平,以及它们在粪便培养物中的生成/降解动力学。吲哚和对甲酚的浓度,挥发物,干重,并分析了10名健康成年人粪便中铵和碳水化合物的含量。吲哚和对甲酚在样品中差异很大,铺设范围为1.0-19.5μg/g和1.2-173.4μg/g,分别。较高的吲哚和对甲酚的粪便水平与较低的碳水化合物和较高的铵水平有关,它们是更明显的肠道蛋白水解代谢的标志。也观察到与干/湿重比的正相关。粪便肠道滞留时间延长的指标。对甲酚和吲哚与未培养的拟杆菌和Firmicutes的OTU呈统计学显着负相关,前者属于拟杆菌属,后者属于Butyricicocycaceae(Butyricicocus属),单球科(单球属),Lachnospirosaceae(粪杆菌属,罗斯布里亚,和文氏真杆菌组)。在粪便浆液中研究了吲哚和对甲酚的形成和/或降解动力学,在严格的厌氧症中补充前体氨基酸色氨酸和酪氨酸。前体的存在使吲哚的产生破裂,但对对甲酚的形成速率影响较低。另一方面,补充吲哚会降低净形成率。在生物转化实验中,与尿毒症毒素的粪便水平呈正相关的分类单元也与对甲酚的产生率呈正相关。此外,其他细菌组与对甲酚和吲哚的生成率呈正相关,进一步扩大与对甲酚生产相关的分类单元的范围(拟杆菌,Alistipes,木聚糖真杆菌,和Barnesiella)和吲哚(例如,拟杆菌,Ruminococcus扭矩,Balutia,Dialister,Butyricicocus)。本文提供的信息有助于揭示微生物群组成与尿毒症毒素产生之间的关系,这可以为益生菌干预肠道微生物群提供基础,旨在防止发病,阻碍进展,减轻肾病的影响。
Indole and p-cresol are precursors of the most important uremic toxins, generated from the fermentation of amino acids tryptophan and tyrosine by the proteolytic community of intestinal bacteria. The present study focused on the relationship between the microbiome composition, the fecal levels of
indole and p-cresol, and their kinetics of generation/degradation in fecal cultures. The concentration of
indole and p-cresol, the volatilome, the dry weight, and the amount of ammonium and carbohydrates were analyzed in the feces of 10 healthy adults.
Indole and p-cresol widely differed among samples, laying in the range of 1.0-19.5 μg/g and 1.2-173.4 μg/g, respectively. Higher fecal levels of indole and p-cresol were associated with lower carbohydrates and higher ammonium levels, that are markers of a more pronounced intestinal proteolytic metabolism. Positive relationship was observed also with the dry/wet weight ratio, indicator of prolonged intestinal retention of feces. p-cresol and indole presented a statistically significant negative correlation with OTUs of uncultured Bacteroidetes and Firmicutes, the former belonging to Bacteroides and the latter to the families Butyricicoccaceae (genus Butyricicoccus), Monoglobaceae (genus Monoglobus), Lachnospiraceae (genera Faecalibacterium, Roseburia, and Eubacterium ventriosum group). The kinetics of formation and/or degradation of indole and p-cresol was investigated in fecal slurries, supplemented with the precursor amino acids tryptophan and tyrosine in strict anaerobiosis. The presence of the precursors bursted indole production but had a lower effect on the rate of p-cresol formation. On the other hand, supplementation with
indole reduced the net rate of formation. The taxa that positively correlated with fecal levels of uremic toxins presented a positive correlation also with p-cresol generation rate in biotransformation experiments. Moreover other bacterial groups were positively correlated with generation rate of p-cresol and indole, further expanding the range of taxa associated to production of p-cresol (Bacteroides, Alistipes, Eubacterium xylanophylum, and Barnesiella) and indole (e.g., Bacteroides, Ruminococcus torques, Balutia, Dialister, Butyricicoccus). The information herein presented contributes to disclose the relationships between microbiota composition and the production of uremic toxins, that could provide the basis for probiotic intervention on the gut microbiota, aimed to prevent the onset, hamper the progression, and alleviate the impact of nephropaties.