Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.
Caelus Pharmaceuticals, Zegveld, The Netherlands.
Nat Commun. 2021 Aug 10;12(1):4798. doi: 10.1038/s41467-021-25081-w.
We describe the anaerobic conversion of inositol stereoisomers to propionate and acetate by the abundant intestinal genus Anaerostipes. A inositol pathway was elucidated by nuclear magnetic resonance using [C]-inositols, mass spectrometry and proteogenomic analyses in A. rhamnosivorans, identifying 3-oxoacid CoA transferase as a key enzyme involved in both 3-oxopropionyl-CoA and propionate formation. This pathway also allowed conversion of phytate-derived inositol into propionate as shown with [C]-phytate in fecal samples amended with A. rhamnosivorans. Metabolic and (meta)genomic analyses explained the adaptation of Anaerostipes spp. to inositol-containing substrates and identified a propionate-production gene cluster to be inversely associated with metabolic biomarkers in (pre)diabetes cohorts. Co-administration of myo-inositol with live A. rhamnosivorans in western-diet fed mice reduced fasting-glucose levels comparing to heat-killed A. rhamnosivorans after 6-weeks treatment. Altogether, these data suggest a potential beneficial role for intestinal Anaerostipes spp. in promoting host health.
我们描述了丰富的肠道属 Anaerostipes 如何将肌醇立体异构体转化为丙酸和乙酸。通过使用 [C]-肌醇、质谱和 Anaerostipes rhamnosivorans 的蛋白质组学分析，阐明了核磁共振的肌醇途径，确定 3-氧代酸 CoA 转移酶是参与 3-氧代丙酰 CoA 和丙酸形成的关键酶。该途径还允许植酸盐衍生的肌醇转化为丙酸，如用 [C]-植酸盐在添加 Anaerostipes rhamnosivorans 的粪便样本中所示。代谢和（宏）基因组学分析解释了 Anaerostipes spp. 对含肌醇底物的适应，并确定了一个丙酸生成基因簇与（前）糖尿病队列中的代谢生物标志物呈负相关。在西方饮食喂养的小鼠中，与热灭活的 Anaerostipes rhamnosivorans 相比，施用含有肌醇的 Anaerostipes rhamnosivorans 活菌可降低空腹血糖水平，治疗 6 周后效果更为明显。总之，这些数据表明肠道 Anaerostipes spp. 可能对促进宿主健康具有潜在的有益作用。
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