Abstract
Ischemic stroke (IS), as a leading cause of disability worldwide, affects intestinal bacterial communities and their metabolites, while recent discoveries have highlighted the importance of the intestinal microflora in the development of IS. Systematic investigations of complex intestinal bacterial communities and their metabolites during ischemic brain injury contribute to elucidate the promising therapeutic targets for IS. However, the associations between intestinal microbiota and related circulating metabolic processes in IS remained unclear. Hence, to identify the changed microflora and their metabolites in IS of NaoMaiTong (NMT), an effective clinical medication, we established the middle cerebral artery occlusion/reperfusion (MCAO/R) model using conventionalized and pseudo-germ-free (PGF) rats. Subsequently, we systematically screen the microflora and related metabolites changing in IS via an integrated approach of cecal 16S rRNA sequencing combined with plasma metabolomics. We found that NMT relied on intestinal flora to improve stroke outcome in conventionalized rats while the protection of NMT was reduced in PGF rats. Total 35 differential bacterial genera and 26 differential microbial metabolites were regulated by NMT. Furthermore, L-asparagine and indoleacetaldehyde were significantly negatively correlated with Lachnospiraceae_UCG.001 and significantly positively correlated with Lachnoclostridium. Indoleacetaldehyde also presented a negative correlation with Lactobacillus and Bifidobacterium. 2-Hydroxybutyric acid was strongly negatively correlated with Ruminococcus, Lachnospiraceae_UCG.001 and Lachnospiraceae_UCG.006. Creatinine was strongly negatively correlated with Akkermansia. In summary, the research provided insights into the intricate interaction between intestinal microbiota and metabolism of NMT in IS. We identified above differential bacteria and differential endogenous metabolites which could be as prebiotic and probiotic substances that can influence prognosis in stroke and have potential to be used as novel therapeutic targets or exogenous drug supplements.
Highlights
Ischemic stroke (IS), a 80–85% proportion of all types of stroke, is characterized by loss of neurological function and long-term disability (Musuka et al, 2015)
The score of neurological function and beam balance test of the model rats were significantly lower than the sham rats, but significantly enhanced after NMT administration which indicated that NMT improved the spontaneous exercise and balance capability of model rats (Figures 1C,D)
Indoleacetaldehyde presented the negative correlation with Lactobacillus and Bifidobacterium. 2-Hydroxybutyric acid was strongly negatively correlated with Ruminococcus, Lachnospiraceae_UCG.001 and Lachnospiraceae_UCG.006
Summary
Ischemic stroke (IS), a 80–85% proportion of all types of stroke, is characterized by loss of neurological function and long-term disability (Musuka et al, 2015). Due to the complicated and unclear pathological mechanism of IS, it restricts the development of new drugs for the treatment of IS. The reestablishment of intestinal flora feeds back to relieve neuroinflammation and promote stroke prognosis through the communication pathways such as the immune system (Benakis et al, 2016; Sadler et al, 2020), endocranium (Houlden et al, 2016), nervous system (Kurita et al, 2020; Xu et al, 2020), and humoral routes (Benakis et al, 2016; Singh et al, 2016; Kurita et al, 2020; Lee et al, 2020). Exploration of the role of gut bacteria changing in IS was vital for the identification of novel treatments
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
