Translational Research Center for Gastrointestinal Disorders and Leuven Food Science and Nutrition Research Centre, University Hospital Gasthuisberg, KU Leven Leuven, Belgium.
PLoS One. 2012;7(12):e52387. doi: 10.1371/journal.pone.0052387. Epub 2012 Dec 20.
Protein fermentation results in production of metabolites such as ammonia, amines and indolic, phenolic and sulfur-containing compounds. In vitro studies suggest that these metabolites might be toxic. However, human and animal studies do not consistently support these findings. We modified protein fermentation in healthy subjects to assess the effects on colonic metabolism and parameters of gut health, and to identify metabolites associated with toxicity.
After a 2-week run-in period with normal protein intake (NP), 20 healthy subjects followed an isocaloric high protein (HP) and low protein (LP) diet for 2 weeks in a cross-over design. Protein fermentation was estimated from urinary p-cresol excretion. Fecal metabolite profiles were analyzed using GC-MS and compared using cluster analysis. DGGE was used to analyze microbiota composition. Fecal water genotoxicity and cytotoxicity were determined using the Comet assay and the WST-1-assay, respectively, and were related to the metabolite profiles.
Dietary protein intake was significantly higher during the HP diet compared to the NP and LP diet. Urinary p-cresol excretion correlated positively with protein intake. Fecal water cytotoxicity correlated negatively with protein fermentation, while fecal water genotoxicity was not correlated with protein fermentation. Heptanal, 3-methyl-2-butanone, dimethyl disulfide and 2-propenyl ester of acetic acid are associated with genotoxicity and indole, 1-octanol, heptanal, 2,4-dithiapentane, allyl-isothiocyanate, 1-methyl-4-(1-methylethenyl)-benzene, propionic acid, octanoic acid, nonanoic acid and decanoic acid with cytotoxicity.
This study does not support a role of protein fermentation in gut toxicity. The identified metabolites can provide new insight into colonic health.
ClinicalTrial.gov NCT01280513.
蛋白质发酵会产生代谢产物，如氨、胺、吲哚、酚和含硫化合物。体外研究表明，这些代谢产物可能具有毒性。然而，人体和动物研究并不一致支持这些发现。我们改变了健康受试者的蛋白质发酵，以评估其对结肠代谢和肠道健康参数的影响，并确定与毒性相关的代谢产物。
在正常蛋白质摄入（NP）的 2 周适应期后，20 名健康受试者以交叉设计的方式进行了 2 周的等热量高蛋白（HP）和低蛋白（LP）饮食。通过尿对甲酚排泄来估计蛋白质发酵。使用 GC-MS 分析粪便代谢物谱，并使用聚类分析进行比较。DGGE 用于分析微生物群落组成。使用彗星试验和 WST-1 试验分别测定粪便水的遗传毒性和细胞毒性，并将其与代谢物谱相关联。
HP 饮食时的膳食蛋白质摄入量明显高于 NP 和 LP 饮食。尿对甲酚排泄与蛋白质摄入量呈正相关。粪便水细胞毒性与蛋白质发酵呈负相关，而粪便水遗传毒性与蛋白质发酵无关。庚醛、3-甲基-2-丁酮、二甲基二硫醚和乙酸 2-丙烯酯与遗传毒性有关，吲哚、1-辛醇、庚醛、2,4-二硫戊烷、烯丙基异硫氰酸酯、1-甲基-4-（1-甲基乙烯基）-苯、丙酸、辛酸、壬酸和癸酸与细胞毒性有关。
本研究不支持蛋白质发酵在肠道毒性中的作用。所鉴定的代谢产物可为结肠健康提供新的见解。
ClinicalTrial.gov NCT01280513。
