Objective Although gut dysbiosis is increasingly recognised as a pathophysiological component of metabolic syndrome (MetS), the role and mode of action of specific gut microbes in metabolic health remain elusive. Previously, we identified the commensal butyrogenic Anaerobutyricum soehngenii to be associated with improved insulin sensitivity in subjects with MetS. In this proof-of-concept study, we investigated the potential therapeutic effects of A. soehngenii L2-7 on systemic metabolic responses and duodenal transcriptome profiles in individuals with MetS. Design In this randomised double-blind placebo-controlled cross-over study, 12 male subjects with MetS received duodenal infusions of A. soehngenii / placebo and underwent duodenal biopsies, mixed meal tests (6 hours postinfusion) and 24-hour continuous glucose monitoring. Results A. soehngenii treatment provoked a markedly increased postprandial excursion of the insulinotropic hormone glucagon-like peptide 1 (GLP-1) and an elevation of plasma secondary bile acids, which were positively associated with GLP-1 levels. Moreover, A. soehngenii treatment robustly shaped the duodenal expression of 73 genes, with the highest fold induction in the expression of regenerating islet-protein 1B ( REG1B )-encoding gene. Strikingly, duodenal REG1B expression positively correlated with GLP-1 levels and negatively correlated with peripheral glucose variability, which was significantly diminished in the 24 hours following A. soehngenii intake. Mechanistically, Reg1B expression is induced upon sensing butyrate or bacterial peptidoglycan. Importantly, A. soehngenii duodenal administration was safe and well tolerated. Conclusions A single dose of A. soehngenii improves peripheral glycaemic control within 24 hours; it specifically stimulates intestinal GLP-1 production and REG1B expression. Further studies are needed to delineate the specific pathways involved in REG1B induction and function in insulin sensitivity. Trial registration number NTR-NL6630. All data relevant to the study are included in the article or uploaded as supplementary information.

中文翻译：

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十二指肠 Anaerobutyricum soehngenii 输液刺激 GLP-1 的产生，改善血糖控制并有益地塑造代谢综合征受试者的十二指肠转录组：一项随机双盲安慰剂对照交叉研究

目的虽然肠道菌群失调越来越被认为是代谢综合征（MetS）的一个病理生理组成部分，但特定肠道微生物在代谢健康中的作用和作用方式仍然难以捉摸。以前，我们发现共生丁酸 Anaerobutyricum soehngenii 与 MetS 受试者的胰岛素敏感性改善有关。在这项概念验证研究中，我们研究了 A. soehngenii L2-7 对 MetS 个体的全身代谢反应和十二指肠转录组谱的潜在治疗作用。设计 在这项随机双盲安慰剂对照交叉研究中，12 名 MetS 男性受试者接受十二指肠输注 A. soehngenii/安慰剂，并接受十二指肠活检、混合膳食测试（输注后 6 小时）和 24 小时连续血糖监测。结果 A。soehngenii 治疗引起了促胰岛素激素胰高血糖素样肽 1 (GLP-1) 的餐后漂移显着增加和血浆次级胆汁酸的升高，这与 GLP-1 水平呈正相关。此外，A. soehngenii 处理有力地塑造了 73 个基因的十二指肠表达，其中对再生胰岛蛋白 1B (REG1B) 编码基因的表达具有最高的诱导倍数。引人注目的是，十二指肠 REG1B 表达与 GLP-1 水平呈正相关，与外周葡萄糖变异性呈负相关，后者在 A. soehngenii 摄入后 24 小时内显着降低。从机制上讲，Reg1B 表达是在感应丁酸或细菌肽聚糖时诱导的。重要的是，A. soehngenii 十二指肠给药是安全且耐受性良好的。结论 单剂量 A. soehngenii 可在 24 小时内改善外周血糖控制；它特异性地刺激肠道 GLP-1 的产生和 REG1B 的表达。需要进一步的研究来描述参与 REG1B 诱导和胰岛素敏感性功能的特定途径。试用注册号 NTR-NL6630。所有与研究相关的数据都包含在文章中或作为补充信息上传。