Zabolotneva Anastasia A, Gaponov Andrei M, Roumiantsev Sergey A, Vasiliev Ilya Yu, Grigoryeva Tatiana V, Kit Oleg I, Zlatnik Elena Yu, Maksimov Aleksey Yu, Goncharova Anna S, Novikova Inna A, Appolonova Svetlana A, Markin Pavel A, Shestopalov Aleksandr V
Department of Biochemistry and Molecular Biology, Faculty of Medicine, N. I. Pirogov Russian National Research Medical University, 1 Ostrovitianov Str., Moscow 117997, Russia.
Russian National Medical Research Center for Endocrinology, 11 Dm. Ulyanova Str., Moscow 117036, Russia.
Int J Mol Sci. 2023 Sep 18;24(18):14206. doi: 10.3390/ijms241814206.
Alkylresorcinols (ARs) are polyphenolic compounds with a wide spectrum of biological activities and are potentially involved in the regulation of host metabolism. The present study aims to establish whether ARs can be produced by the human gut microbiota and to evaluate alterations in content in stool samples as well as metabolic activity of the gut microbiota of C57BL, , and LDLR (-/-) mice according to diet specifications and olivetol (5-n-pentylresorcinol) supplementation to estimate the regulatory potential of ARs. Gas chromatography with mass spectrometric detection was used to quantitatively analyse AR levels in mouse stool samples; faecal microbiota transplantation (FMT) from human donors to germ-free mice was performed to determine whether the intestinal microbiota could produce AR molecules; metagenome sequencing analysis of the mouse gut microbiota followed by reconstruction of its metabolic activity was performed to investigate olivetol's regulatory potential. A significant increase in the amounts of individual members of AR homologues in stool samples was revealed 14 days after FMT. Supplementation of 5-n-Pentylresorcinol to a regular diet influences the amounts of several ARs in the stool of C57BL/6 and LDLR (-/-) but not mice, and caused a significant change in the predicted metabolic activity of the intestinal microbiota of C57BL/6 and LDLR (-/-) but not mice. For the first time, we have shown that several ARs can be produced by the intestinal microbiota. Taking into account the dependence of AR levels in the gut on olivetol supplementation and microbiota metabolic activity, AR can be assumed to be potential molecules, which also influence gut microbiota composition and host metabolism.
烷基间苯二酚(ARs)是一类具有广泛生物活性的多酚类化合物,可能参与宿主代谢的调节。本研究旨在确定ARs是否可由人体肠道微生物群产生,并根据饮食规格和橄榄醇(5 - 正戊基间苯二酚)补充情况,评估C57BL、LDLR(-/-)小鼠粪便样本中ARs含量的变化以及肠道微生物群的代谢活性,以估计ARs的调节潜力。采用气相色谱 - 质谱检测法定量分析小鼠粪便样本中的AR水平;将人类供体的粪便微生物群移植(FMT)到无菌小鼠体内,以确定肠道微生物群是否能产生AR分子;对小鼠肠道微生物群进行宏基因组测序分析,随后重建其代谢活性,以研究橄榄醇的调节潜力。FMT后14天,粪便样本中AR同系物的个别成员数量显著增加。在常规饮食中补充5 - 正戊基间苯二酚会影响C57BL/6和LDLR(-/-)小鼠粪便中几种ARs的含量,但对小鼠无影响,并且会导致C57BL/6和LDLR(-/-)小鼠肠道微生物群的预测代谢活性发生显著变化,但对小鼠无影响。我们首次表明,几种ARs可由肠道微生物群产生。考虑到肠道中AR水平对橄榄醇补充和微生物群代谢活性的依赖性,可以认为AR是潜在的分子,其也会影响肠道微生物群组成和宿主代谢。