Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, Russia.
The Laboratory of Ecological Genetics, Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia.
Microbiol Spectr. 2024 Nov 5;12(11):e0063624. doi: 10.1128/spectrum.00636-24. Epub 2024 Sep 30.
Inflammatory bowel diseases are characterized by chronic intestinal inflammation and alterations in the gut microbiota composition. , which secretes outer membrane vesicles (OMVs) with polysaccharide A (PSA), can moderate the inflammatory response and possibly alter the microbiota composition. In this study, we created a murine model of chronic sodium dextran sulfate (DSS)-induced intestinal colitis and treated it with OMVs. We monitored the efficiency of OMV therapy by determining the disease activity index (DAI) and performing histological examination (HE) of the intestine before and after vesicle exposure. We also analyzed the microbiota composition using 16S rRNA gene sequencing. Finally, we evaluated the volatile compound composition in the animals' stools by HS-GC/MS to assess the functional activity of the microbiota. We observed more effective intestinal repair after OMV treatment according to the DAI and HE. A metabolomic study also revealed changes in the functional activity of the microbiota, with a predominance of phenol and pentanoic acid in the control group compared to the group treated with DSS and the group treated with OMVs (DSS OMVs). We also observed a positive correlation of these metabolites with and in the control group, whereas in the DSS group, there was a negative correlation of phenol and pentanoic acid with and . According to the metabolome and sequencing data, the microbiota composition of the DSS-treated OMV group was intermediate between that of the control and DSS groups. OMVs not only have an anti-inflammatory effect but also contribute to the recovery of the microbiota composition.IMPORTANCE vesicles contain superficially localized polysaccharide A (PSA), which has unique immune-modulating properties. Isolated PSA can prevent chemically induced colitis in a murine model. Outer membrane vesicles (OMVs) also contain digestive enzymes and volatile metabolites that can complement the anti-inflammatory properties of PSA. OMVs showed high therapeutic activity against sodium dextran sulfate-induced colitis, as confirmed by histological assays. 16S rRNA sequencing of fecal samples from different inflammatory stages, supplemented with comprehensive metabolome analysis of volatile compounds conducted by HS-GC/MS, revealed structural and functional alterations in the microbiota composition under the influence of OMVs. Correlation analysis of the OMV-treated and untreated experimental animal groups revealed associations of phenol and pentanoic acid with , , , and .
炎症性肠病的特征是慢性肠道炎症和肠道微生物群落组成的改变。 ，它分泌具有多糖 A（PSA）的外膜囊泡（OMV），可以调节炎症反应，并可能改变微生物群落组成。在这项研究中，我们创建了一个慢性葡聚糖硫酸钠（DSS）诱导的肠道结肠炎的小鼠模型，并使用 OMV 进行了治疗。我们通过在暴露囊泡前后确定疾病活动指数（DAI）和对肠道进行组织学检查（HE）来监测 OMV 治疗的效率。我们还使用 16S rRNA 基因测序分析了微生物群落的组成。最后，我们通过 HS-GC/MS 评估动物粪便中的挥发性化合物组成，以评估微生物群落的功能活性。我们观察到 OMV 治疗后肠道修复更有效，根据 DAI 和 HE 得出的结果。代谢组学研究还揭示了微生物群落功能活性的变化，与对照组相比，DSS 组和 DSS OMV 组中酚和戊酸的含量较高。我们还观察到这些代谢物与对照组中的 呈正相关，而在 DSS 组中，酚和戊酸与 呈负相关。根据代谢组学和测序数据，DSS 处理的 OMV 组的微生物群落组成介于对照组和 DSS 组之间。OMV 不仅具有抗炎作用，而且有助于恢复微生物群落组成。
囊泡含有表面定位的多糖 A（PSA），具有独特的免疫调节特性。分离的 PSA 可预防小鼠模型中的化学诱导性结肠炎。外膜囊泡（OMV）还含有消化酶和挥发性代谢物，可补充 PSA 的抗炎特性。OMV 对葡聚糖硫酸钠诱导的结肠炎具有高治疗活性，通过组织学检测得到证实。来自不同炎症阶段的粪便样本的 16S rRNA 测序，补充了通过 HS-GC/MS 进行的挥发性化合物的综合代谢组分析，揭示了在 OMV 影响下微生物群落组成的结构和功能改变。对 OMV 处理和未处理的实验组动物群进行相关分析，揭示了酚和戊酸与 、 、 、 和 的相关性。
