Microbially catalyzed conjugation of GABA and tyramine to bile acids.
Microbially catalyzed conjugation of GABA and tyramine to bile acids.
复制标题
DOI：
10.1128/jb.00426-23
复制
发表时间：
2024-01-25
影响因子：
3.2
通讯作者：
Crosson, Sean
中科院分区：
文献类型：
--
作者：
Mullowney, Michael W.;Fiebig, Aretha;Schnizlein, Matthew K.;McMillin, Mary;Rose, Amber R.;Koval, Jason;Rubin, David;Dalal, Sushila;Sogin, Mitchell L.;Chang, Eugene B.;Sidebottom, Ashley M.;Crosson, Sean
关键词：
胆汁酸(BAs)是胆固醇衍生的分子，有助于消化和营养吸收，调节宿主代谢过程，并影响肠道微生物区系的生理。宿主和它的微生物群都有助于酶的修饰，从而塑造肠道中BAs的化学多样性。据报道，有几种细菌能将标准氨基酸与bas结合，但尚不清楚细菌是否会将bas与其他胺类结合。在这里，我们展示了从溃疡性结肠炎患者J袋中的细菌水华中分离出来的脆弱类杆菌P207菌株，它将标准氨基酸与神经活性胺γ-氨基丁酸和酪胺偶联为脱氧胆酸。我们将这一分析扩展到其他人类肠道分离株，并确定了有能力将GABA和酪胺结合到初级和次级BA的物种，并进一步在人类粪便中鉴定了不同的BA-GABA和BA-酪胺酰胺。对分离出脆弱芽孢杆菌P207的患者的J袋内容物进行的纵向代谢分析显示，在膀胱炎发作之前、期间和之后，次级胆汁酸水平显著降低，BA酰胺谱发生变化，包括几种BA-GABA酰胺的时间变化。环丙沙星治疗膀胱炎与J袋中几乎所有BA酰胺的显著减少有关。我们的研究扩展了已知的细菌产生的结合胆汁酸的谱系，包括BA与GABA和酪胺的结合，并证明这些分子存在于人类肠道中。BA被宿主酶和微生物区系以多种方式修饰，以产生一组化学上不同的分子，帮助消化过程并影响许多生理功能。这项研究报告了一种细菌的发现，这种细菌结合了神经活性胺、GABA和酪胺，使其与初级和次级BA结合。我们进一步提出了BA-GABA和BA-酪胺结合物存在于人的肠道中的证据，并记录了在炎症和抗生素治疗之前、期间和之后人类膀胱炎患者中BA-GABA的变化。GABA和酪胺是肠道微生物区系和强大的神经活性分子共同的代谢产物。GABA和酪胺偶联的BA可能会影响人体和肠道微生物的受体介导的调节机制，这些分子的吸收和进入肠肝循环可能会影响远端组织部位的宿主生理。这项研究定义了人体肠道中新的结合胆汁酸。
Bile acids (BAs) are cholesterol-derived molecules that aid in digestion and nutrient absorption, regulate host metabolic processes, and influence physiology of the gut microbiota. Both the host and its microbiome contribute to enzymatic modifications that shape the chemical diversity of BAs in the gut. Several bacterial species have been reported to conjugate standard amino acids to BAs, but it was not known if bacteria conjugate BAs to other amine classes. Here, we show that Bacteroides fragilis strain P207, isolated from a bacterial bloom in the J-pouch of a patient with ulcerative colitis pouchitis, conjugates standard amino acids and the neuroactive amines γ-aminobutyric acid (GABA) and tyramine to deoxycholic acid. We extended this analysis to other human gut isolates and identified species that are competent to conjugate GABA and tyramine to primary and secondary BAs, and further identified diverse BA-GABA and BA-tyramine amides in human stool. A longitudinal metabolomic analysis of J-pouch contents of the patient from whom B. fragilis P207 was isolated revealed highly reduced levels of secondary bile acids and a shifting BA amide profile before, during, and after onset of pouchitis, including temporal changes in several BA-GABA amides. Treatment of pouchitis with ciprofloxacin was associated with a marked reduction of nearly all BA amides in the J-pouch. Our study expands the known repertoire of conjugated bile acids produced by bacteria to include BA conjugates to GABA and tyramine and demonstrates that these molecules are present in the human gut. BAs are modified in multiple ways by host enzymes and the microbiota to produce a chemically diverse set of molecules that assist in the digestive process and impact many physiological functions. This study reports the discovery of bacterial species that conjugate the neuroactive amines, GABA and tyramine, to primary and secondary BAs. We further present evidence that BA-GABA and BA-tyramine conjugates are present in the human gut, and document a shifting BA-GABA profile in a human pouchitis patient before, during, and after inflammation and antibiotic treatment. GABA and tyramine are common metabolic products of the gut microbiota and potent neuroactive molecules. GABA- and tyramine-conjugated BAs may influence receptor-mediated regulatory mechanisms of humans and their gut microbes, and absorption of these molecules and their entry into enterohepatic circulation may impact host physiology at distal tissue sites. This study defines new conjugated bile acids in the human gut.
登录
查看更多内容
影响因子：
3.7
作者：
Gotoh K;Kodama T;Hiyoshi H;Izutsu K;Park KS;Dryselius R;Akeda Y;Honda T;Iida T
通讯作者：
Iida T
影响因子：
5.8
作者：
Horvath, Thomas D.;Ihekweazu, Faith D.;Haidacher, Sigmund J.;Ruan, Wenly;Engevik, Kristen A.;Fultz, Robert;Hoch, Kathleen M.;Luna, Ruth Ann;Oezguen, Numan;Spinler, Jennifer K.;Haag, Anthony M.;Versalovic, James;Engevik, Melinda A.
通讯作者：
Engevik, Melinda A.
影响因子：
28.3
作者：
Foley, Matthew H.;Walker, Morgan E.;Stewart, Allison K.;O'Flaherty, Sarah;Gentry, Emily C.;Patel, Shakshi;Beaty, Violet V.;Allen, Garrison;Pan, Meichen;Simpson, Joshua B.;Perkins, Caroline;Vanhoy, Molly E.;Dougherty, Michael K.;McGill, Sarah K.;Gulati, Ajay S.;Dorrestein, Pieter C.;Baker, Erin S.;Redinbo, Matthew R.;Barrangou, Rodolphe;Theriot, Casey M.
通讯作者：
Theriot, Casey M.
影响因子：
6.4
作者：
Lucas, L. N.;Barrett, K.;Amador-Noguez, D.
通讯作者：
Amador-Noguez, D.
影响因子：
4.8
作者：
Kawamata, Y;Fujii, R;Fujino, M
通讯作者：
Fujino, M