PharmaBiome AG, Schlieren, Switzerland.
Laboratory of Food Biotechnology, Institute of Food, Nutrition and Health, ETH Zurich, Zurich, Switzerland.
Microbiome. 2024 Sep 30;12(1):186. doi: 10.1186/s40168-024-01897-8.
The human gut microbiome produces and consumes a variety of compounds that interact with the host and impact health. Succinate is of particular interest as it intersects with both host and microbiome metabolism. However, which gut bacteria are most responsible for the consumption of intestinal succinate is poorly understood.
We build upon an enrichment-based whole fecal sample culturing approach and identify two main bacterial taxa that are responsible for succinate consumption in the human intestinal microbiome, Phascolarctobacterium and Dialister. These two taxa have the hallmark of a functional guild and are strongly mutual exclusive across 21,459 fecal samples in 94 cohorts and can thus be used to assign a robust "succinotype" to an individual. We show that they differ with respect to their rate of succinate consumption in vitro and that this is associated with higher concentrations of fecal succinate. Finally, individuals suffering from inflammatory bowel disease (IBD) are more likely to have the Dialister succinotype compared to healthy subjects.
We identified that only two bacterial genera are the key succinate consumers in human gut microbiome, despite the fact that many more intestinal bacteria encode for the succinate pathway. This highlights the importance of phenotypic assays in functionally profiling intestinal microbiota. A stratification based on "succinotype" is to our knowledge the first function-based classification of human intestinal microbiota. The association of succinotype with IBD thus builds a bridge between microbiome function and IBD pathophysiology related to succinate homeostasis. Video Abstract.
人类肠道微生物组产生和消耗多种与宿主相互作用并影响健康的化合物。琥珀酸特别引人注目，因为它与宿主和微生物组代谢都有关联。然而，肠道中哪些细菌最负责消耗肠道中的琥珀酸还知之甚少。
我们在基于富集的全粪便样本培养方法的基础上，确定了两种主要的细菌类群，它们负责人类肠道微生物组中琥珀酸的消耗，即 Phascolarctobacterium 和 Dialister。这两个类群具有功能群的标志，在 94 个队列的 21459 个粪便样本中是强烈相互排斥的，因此可以用来为个体分配一个稳健的“琥珀酸型”。我们表明，它们在体外琥珀酸消耗率方面存在差异，这与粪便中琥珀酸浓度较高有关。最后，患有炎症性肠病（IBD）的个体比健康个体更有可能具有 Dialister 琥珀酸型。
尽管许多肠道细菌都编码琥珀酸途径，但我们发现只有两个细菌属是人类肠道微生物组中琥珀酸的主要消耗者。这突出了表型测定在功能上对肠道微生物组进行分析的重要性。基于“琥珀酸型”的分层是我们所知的第一个基于功能的人类肠道微生物组分类。因此，琥珀酸型与 IBD 的关联在微生物组功能和与琥珀酸动态平衡相关的 IBD 病理生理学之间架起了一座桥梁。视频摘要。
