| Yin J, et al. (2015) (48) |
322 patients vs. 231 controls |
16S rRNA (V4) sequencing & LC-MS |
Patients with stroke and transient ischemic attack presented the gut microbiota dysbiosis, which increased Enterobacter, Megasphaera, Oscillibacter, and Desulfovibrio and decreased Bacteroides, Prevotella, and Faecalibacterium. Patients with stroke and the transient ischemic attack had lower trimethylamine N-oxide (TMAO) compared with asymptomatic patients.
|
| Stanley D, et al. (2016) (52) |
36 patients vs. 9 hospital-based controls vs. 10 healthy controls;
middle cerebral artery occlusion (MCAO) mice |
16S rRNA sequencing |
Common commensal bacteria resided in the intestinal tracts contributed to the post-stroke infections in patients with ischemic stroke. This was also observed in a mouse model of ischemic stroke. In the experimental stroke, post-stroke infection was only seen in specific pathogen-free (SPF) mice, not germ-free (GF) mice.
|
| Nie J, et al. (2018) (51) |
622 patients vs. 622 controls |
LC-MS |
|
| Zeng X, et al. (2019) (50) |
141 patients |
16S rRNA sequencing & GS-MS |
Compared with the low-risk group, opportunistic pathogens (e.g., Enterobacteriaceae and Veillonellaceae) and lactate-producing bacteria (e.g., Bifidobacterium and Lactobacillus) were increased, as well as butyrate-producing bacteria (e.g., Lachnospiraceae and Ruminococcaceae) were decreased in the high-risk group. The fecal butyrate concentrations in the high-risk group were lower than those in the low-risk group. Moreover, the concentrations of other short-chain fatty acids (SCFAs) (e.g., acetate, propionate, isobutyrate, isovalerate, and valerate) in the feces were significantly different between the three groups.
|
| Haak BW, et al. (2020) (49) |
349 patients vs. 51 controls |
16S rRNA (V3-V4) sequencing & LC-MS |
The TMAO level in stroke patients was two-fold lower than that of the healthy controls. Lower abundance of butyrate-producing bacteria within 24h of hospital admission was an independent predictor of enhanced risk of post-stroke infection, but not of mortality or functional patient outcome.
|
| Xu DJ, et al. (2021) (60) |
61 large artery atherosclerotic (LAA) stroke vs. 20 cardioembolic (CE) stroke vs. 51 asymptomatic controls |
16S rRNA (V4-V5) sequencing & LC-MS |
The TMAO levels in the plasma of patients with LAA and CE strokes were significantly higher than those in controls. Moreover, the plasma TMAO level in the LAA stroke patients was positively associated with the carotid plaque area. The composition and the function of gut microbiota in the patients with LAA stroke were significantly different from those in the asymptomatic controls. In contrast, no significant difference between CE stroke patients and the asymptomatic controls was observed in the present study.
|
| Ling Y, et al. (2020) (61) |
53 patients with post-stroke cognitive impairment (PSCI) vs. 40 patients with post-stroke non-cognitive impairment (PSNCI) |
16S rRNA (V3-V4) sequencing |
Compared with the patient with PSNCI, the abundance of Proteobacteria was highly increased in the patients with PSCI. The abundances of Clostridia, Clostridiales, Lachnospiraceae, and Lachnospiraceae_other were significantly decreased in the patients with PSCI after adjusting to age. The Kyoto Encyclopedia of Genes and Genomes analysis showed the progressive enriched module for folding, sorting, and degradation (chaperones and folding catalysts) and the significantly decreased modules related to metabolisms of cofactors and vitamins, amino acid, and lipid in patients with PSCI.
|
| Xiang L, et al. (2020) (62) |
20 patients vs. 16 controls |
16S rRNA (V3) sequencing |
Stroke patients had fewer Firmicutes than controls. Two optimal bacterial species, Lachnospiraceae (OTU_45) and Bacteroides served as markers of lacunar infarction. Two optimal bacterial species, Bilophila and Lachnospiraceae (OTU_338)), served as markers of non-lacunar acute ischemic infarction. Three optimal bacterial species, Pseudomonas, Sphingomonadaceae, and Akkermansia, served as markers of post-ischemic stroke patients with 15 days of treatment.
|
| Tan C, et al. (2021) (67) |
140 patients vs. 92 controls |
16S rRNA (V4) sequencing & GS-MS |
Patients with acute ischemic stroke are characterized by a lack of SCFAs-producing bacteria (Roseburia, Bacteroides, Lachnospiraceae, Faecalibacterium, Blautia, and Anaerostipes) and an overload of Lactobacillaceae, Akkermansia, Enterobacteriaceae, and Porphyromonadaceae in their feces. The SCFAs levels were negatively related to stroke severity and prognosis. Reduced fecal SCFAs level, especially acetate, was correlated with an increased risk of 3-month unfavorable outcomes.
|
| Zhang J, et al. (2021) (68) |
351 patients vs. 150 controls |
LC-MS |
Patients with an unfavorable outcome had significantly increased plasma TMAO levels on admission. Plasma TMAO levels on admission were an independent predictor of functional outcome and mortality after acute ischemic stroke.
|
| Guo Q, et al. (2021) (69) |
49 patients vs. 30 controls |
16S rRNA (V3-V4) sequencing |
The acute ischemic stroke patients treated with Tanhuo Decoction had a better outcome than the controls on both clinical outcome and gut microbiota characteristics. Tanhuo Decoction treatment significantly decreased the lipopolysaccharide (LPS)-producing bacteria (Bacteroidaceae and Bacteroides) to reduce LPS biosynthesis. The acute ischemic stroke patients treated with Tanhuo Decoction also exhibited the potential to decrease the biosynthesis of trimethylamine (TMA), the precursor of TMAO, and increase TMA’s degradation.
|
| Huang Y, et al. (2021) (63) |
76 patients vs. 19 controls |
16S rRNA (V3-V4) sequencing |
Stroke patients had a significantly higher abundance of Enterococcus and lower abundances of Bacteroides, Escherichia-Shigella, and Megamonas. Compared with stroke patients, patients with post-stroke cognitive impairment had a significantly higher proportion of Enterococcus, Bacteroides, and Escherichia-Shigella and a lower content of Faecalibacterium. Patients with the post-stroke affective disorder had a significantly higher proportion of Bacteroides and Escherichia-Shigella and a lower proportion of Enterococcus and Faecalibacterium.
|
| Sun T, et al. (2021) (70) |
953 patients vs. 953 controls |
LC-MS/MS |
Plasma TMAO levels in patients with ischemic stroke were significantly increased. Higher plasma TMAO levels were correlated with increased odds of ischemic stroke. The adjusted odds ratios for ischemic stroke per 1 μmol/L increase of plasma TMAO was 1.05.
|
| Xu K, et al. (2021) (64) |
Cohort 1: 28 patients vs. 28 controls;
Cohort 2: 124 patients;
MCAO mice |
16S rRNA sequencing |
Enriched Enterobacteriaceae was an independent risk factor for acute ischaemic stroke patients in early-stage recovery. MCAO mice showed rapid gut dysbiosis with Enterobacteriaceae blooming, associated with intestinal ischemia and nitrate production. Enterobacteriaceae exacerbates brain infarction by accelerating LPS/toll-like receptor 4(TLR4)-mediated systemic inflammation. Inhibiting Enterobacteriaceae overgrowth by diminishing nitrate generation or inhibiting nitrate respiration alleviates brain infarction.
|
| Houlden A, et al. (2016) (21) |
MCAO mice |
16S rRNA PCR |
The alteration of the caecal microbiota composition following stroke could be mediated by noradrenaline release from the autonomic nervous system, changing caecal mucoprotein production and goblet cell numbers. Specific changes in Peptococcaceae and Prevotellaceae after stroke were correlated with the severity of the injury.
|
| Singh V, et al. (2016) (54) |
MCAO mice |
16S rRNA (V1-V3) sequencing |
Reduced species diversity and bacterial overgrowth of bacteroidetes were associated with intestinal barrier dysfunction and reduced intestinal motility. GF mice recolonized with poststroke gut microbiota exacerbates infarct volume and functional deficits following stroke, mediated by the migration of intestinal pro-inflammatory T cells to the ischemic brain. Fecal microbiota transplantation (FMT) could normalize brain lesion-induced dysbiosis and improve stroke outcomes.
|
| Benakis C, et al. (2016) (55) |
MCAO mice |
16S rRNA (V4-V5) sequencing |
Antibiotic-induced alterations in the gut microbiota reduced brain injury after ischemic stroke. Dysbiosis following ischemic stroke changed intestinal immune homeostasis, leading to an increase in regulatory T(Treg) cells and a reduction in IL-17+ γδ T cells through altered dendritic cell activity. Moreover, dysbiosis blocked the migration of effector T cells from the gut to the leptomeninges.
|
| Winek K, et al. (2016) (59) |
MCAO mice |
– |
Microbiota-depleted mice stopped the antibiotic cocktail pretreatment 3 days before surgery significantly decreased survival after MCAO. Microbiota-depleted animals treated by continuous antibiotic treatment or colonized with SPF microbiota before surgery rescued from severe acute colitis.
|
| Spychala MS, et al. (2018) (53) |
MCAO mice |
16S rRNA (V4-V5) sequencing |
The Firmicutes to Bacteroidetes ratio in aged mice increased ∼9-fold compared to young. The gut microbiota in the young manipulated by fecal from aged mice increased mortality, decreased behavioral performance, and increased cytokine levels following MCAO, altering the microbiota in the aged by fecal gavage to resemble that of young increased survival and improved recovery following MCAO.
|
| Singh V, et al. (2018) (23) |
MCAO mice |
16S rRNA (V1-V3) sequencing |
Bacterial colonization reduces stroke volumes by increasing cerebral expression of cytokines and microglia/macrophage cell counts. The gut microbiota-mediated neuroprotection was absent in lymphocyte-deficient mice.
|
| Benakis C, et al. (2020) (56) |
MCAO mice |
16S rRNA (V4) sequencing |
Single antibiotic treatment with either ampicillin or vancomycin, but not neomycin, significantly reduced the infarct volume and improved motor sensory function 3 days after stroke. Bacteroidetes S24.7 and the enzymatic pathway for aromatic metabolism were correlated with infarct size. The gut microbiota composition in the ampicillin-treated mice was associated with reduced gut inflammation, a long-term favorable outcome, and a reduction of brain tissue loss. Regulation of SCFAs and tryptophan pathways induced by ampicillin could be predictive of stroke outcomes.
|
| Sadler R, et al. (2020) (57) |
MCAO and photothrombotic (PT) mice |
GC-MS |
SCFAs supplementation in the drinking water significantly improved recovery of limb motor function by altering contralesional cortex connectivity, which is related to SCFAs-dependent changes in spine and synapse densities. A substantial impact of SCFAs on microglial activation contributes to the structural and functional remodeling, mediated by the recruitment of T cells to the infarcted brain.
|
| Lee J, et al. (2020) (58) |
MCAO mice |
16S rRNA (V4) sequencing & LC-MS |
Aged stroke mice transplanted the young fecal improved post-stroke neurological deficits and inflammation, which correlated with higher SCFAs levels and SCFAs-producers such as Bifidobacterium longum, Clostridium symbiosum, Faecalibacterium prausnitzii, and Lactobacillus fermentum.
|
| Jeon J, et al. (2020) (65) |
MCAO pig |
16S rRNA (V3-V4) sequencing |
Compared with pre-stroke populations, the abundance of the Proteobacteria was significantly increased, while the abundances of Firmicutes and lactic acid bacteria Lactobacillus decreased at 3 days poststroke. The gut microbial pattern returned to similar values as prestrike at 5 days poststroke.
|
| Benakis C, et al. (2020) (56) |
MCAO mice |
16S rRNA (V4) sequencing |
Mice treated with a cocktail of antibiotics significantly reduced infarct volume in the acute phase of stroke. Single antibiotic treatment with either ampicillin or vancomycin, but not neomycin, significantly reduced infarct volume and improved neurological function 3 days after stroke. Bacteroidetes S24.7 and the enzymatic pathway for aromatic metabolism were associated with infarct size after stroke. The gut microbiota signature in the ampicillin-treated mice was correlated with reduced intestinal inflammation, long-term favorable outcome and was predictive of SCFAs and tryptophan pathways.
|
| Huang Q, et al. (2021) (71) |
MCAO rat |
16S rRNA (V3-V4) sequencing & GC-MS |
Compared with non-hemorrhagic transformation (HT) rats, the relative abundances of Proteobacteria and Actinobacteria were enriched in HT rats. Total SCFAs levels, especially butyrate and valeric acid, were significantly decreased in the cecal contents of HT rats. The rats colonized with gut microbiota from HT rats showed increased susceptibility to HT.
|
| Zhang P, et al. (2021) (72) |
MCAO mice |
16S rRNA sequencing & HPLC-MS |
Atorvastatin significantly ameliorated neurological defects and reduced microglia-mediated neuroinflammation after experimental stroke. Atorvastatin increased the abundance of Firmicutes and Lactobacillus, decreased Bacteroidetes abundance, increased fecal butyrate level, promoted intestinal barrier function by elevating the expression of claudin-1, occludin and mucoprotein 2, as well as regulated intestinal immune function. Transplantation of atorvastatin-treated mice fecal microbiota alleviated neuroinflammation in MCAO mice.
|
| Huang JT, et al. (2021) (73) |
MCAO mice |
16S rRNA sequencing |
The transplantation of gut microbiota collected from calorie-restriction-treated mice was eligible to have better long-term rehabilitation. Bifidobacterium was enriched in calorie-restriction mice. Bifidobacterium administration improved the long-term rehabilitation of stroke mice
|
| Zhu W, et al. (2021) (74) |
MCAO mice |
16S rRNA (V4) sequencing & LC-MS |
The human fecal microbial transplantation study showed TMAO production and stroke severity are transmissible traits. TMAO and choline supplementation exacerbated infarct size and functional impairment. Gut microbial CutC increased host TMAO levels and aggravated cerebral infarct size and functional deficits after stroke.
|
| Wu W, et al. (2021) (66) |
MACO rat |
16S rRNA (V3-V4) sequencing & LC-MS |
The abundance of the Firmicutes phylum was decreased, whereas Proteobacteria and Deferribacteres were increased after stroke. Ruminococcus_sp_15975 might serve as a biomarker for the stroke. Many metabolites, such as L-leucine, L-valine, and L-phenylalanine, differed between the stroke and sham groups, mainly involved in mineral absorption and cholinergic synapse pathways.
|
| Yuan Q, et al. (2021) (75) |
MCAO mice |
16S rRNA sequencing & GC-MS |
Lactulose supplementation significantly improved the functional outcome after stroke by downregulating inflammatory reaction and increased anti-inflammatory factors in the brain and gut. Lactulose supplementation improved intestinal barrier injury and restored gut microbiota dysbiosis after stroke.
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