The Bridge Between Ischemic Stroke and Gut Microbes: Short-Chain Fatty Acids.
Cellular and molecular neurobiology
Short-chain fatty acids (SCFAs) are monocarboxylates produced by the gut microbiota (GM) and result from the interaction between diet and GM. An increasing number of studies about the microbiota-gut-brain axis (MGBA) indicated that SCFAs may be a crucial mediator in the MGBA, but their roles have not been fully clarified. In addition, there are few studies directly exploring the role of SCFAs as a potential regulator of microbial targeted interventions in ischemic stroke, especially for clinical studies. This review summarizes the recent studies concerning the relationship between ischemic stroke and GM and outlines the role of SCFAs as a bridge between them. The potential mechanisms by which SCFAs affect ischemic stroke are described. Finally, the beneficial effects of SFCAs-mediated therapeutic measures such as diet, dietary supplements (e.g., probiotics and prebiotics), fecal microbiota transplantation, and drugs on ischemic brain injury are also discussed.
10.1007/s10571-022-01209-4
Is on-admission capillary blood beta-hydroxybutyrate concentration associated with the acute stroke severity and short-term functional outcome?
Pikija Slaven,Trkulja Vladimir,Simundic Ana-Maria,Vrcek Emina,Boskovic Katarina,Bacani Suzana
Neurological research
OBJECTIVES:In conditions with reduced glucose levels/inability of glucose utilization, ketone bodies, especially beta-hydroxybutyrate (BHB), become a major energy source in the brain. In animal models, BHB infusion shows acute beneficial effects on the hypoxic brain. The present prospective observational study is the first to assess the relationship between on-admission capillary blood BHB levels and acute stroke severity/short-term functional outcomes. METHODS:A total of 51 consecutive first-ever stroke patients (46 ischemic stroke) admitted within 24 hours since the symptom onset and ≤ 44 hours since the last meal were evaluated for stroke severity (National institutes of health stroke scale, NIHSS) and for disability (modified Rankin scale, mRS) 3 months post-stroke. RESULTS:On-admission BHB values ranged between 0 and 1.6 mmol/l, with 43 (84.3%) values ≤ 0.4 mmol/l (normal). Higher BHB values were independently associated with longer fasting and hyperglycemia, whereas lower values were associated with dyslipidemia and diabetes. No association between on-admission BHB levels and NIHSS scores at presentation or day 5 was observed. The BHB levels considered either as continuous or as binary (> 0.4 vs ≤ 0.4 mmol/l) variables were independently (adjustment for age, NIHSS score at presentation, fasting period, stroke type, hyperglycemia, diabetes, and dyslipidemia) associated with lower odds of mRS 0-2 (non-to-mild disability) 3 months post-stroke: OR = 0.09 (95% CI 0.00-0.97, P = 0.047) and OR = 0.07 (95% CI 0.00-0.78, P = 0.028), respectively. DISCUSSION:This preliminary study suggests that higher on-admission BHB values are associated with poorer stroke outcomes and emphasizes the need for further investigations.
10.1179/1743132813Y.0000000239
Study on the correlation between serum indole-3-propionic acid levels and the progression and prognosis of acute ischemic stroke.
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association
OBJECTIVE:This study aimed to explore the correlation between the serum level of indole-3-propionic acid (IPA) and the progression and prognosis of acute cerebral infarction (ACI). METHODS:This study enrolled 197 patients with ACI, and 53 participants from a community-based stroke screening program during the same period were included as the control group. The patients with ACI were divided into quartiles of serum IPA. A logistic regression model was used for comparison. Receiver operating characteristic (ROC) curves were drawn to evaluate the predictive value of the IPA. RESULTS:Compared with the healthy control group, the ACI group had lower serum IPA (P < 0.05). The serum IPA was an independent factor for acute ischemic stroke (OR=0.992, 95% CI: 0.984-0.999, P=0.035). The serum IPA was lower in patients with progressive stroke or poor prognosis than in patients with stable stroke or good prognosis (P < 0.05). Patients with ACI with low serum IPA are prone to progression and poor prognosis. The best cutoff value for predicting progression was 193.62 pg/mL (sensitivity, 67.5%; specificity 83.7%), and that for poor prognosis was 193.77 pg/mL (sensitivity, 71.1%; specificity, 72.5%). CONCLUSION:The serum level of IPA was an independent predictor of ACI and had certain clinical value for predicting stroke progression and prognosis in patients with ACI.
10.1016/j.jstrokecerebrovasdis.2024.107680
Gut microbiota-derived acetate promotes long-term recovery through angiogenesis guided by lymphatic ingrowth in older adults with stroke.
Frontiers in neuroscience
Introduction:Ischemic stroke is a leading cause of morbidity and mortality in older adults. Therefore, in this study, we sought to understand the interplay between the microbiota, gut, and brain in the context of stroke in older adults. Objective:To determine whether gut microbiota from younger individuals promotes recovery through angiogenesis in both elderly stroke patients and aged stroke mice, we explored the changes in gut microbiota and the correlation between short-chain fatty acids (SCFAs) and angiogenesis in the aged stroke population. Then, we altered the gut microbiome in aged mice by transplanting microbiota from younger donors before inducing experimental stroke to explore the mechanism by which gut microbiota-derived SCFAs promote angiogenesis. Methods:Part I: We conducted a single-center, double-blind trial to compare gut microbiota diversity and SCFA levels in fecal samples from older stroke patients with those from younger stroke patients. Additionally, we measured levels of vascular endothelial growth factor (VEGF) and VEGFC levels in plasma to assess their correlation with SCFA levels. Part II: We performed fecal microbiota transplantation (FMT) 3 days before inducing ischemic stroke in aged male mice (16-18) via distal middle cerebral artery occlusion (dMCAO). The FMT was conducted using gut microbiomes from either young donors (2-3 months) or aged donors (16-18 months). Results:In older stroke patients, gut microbiota diversity was significantly reduced compared to that in younger stroke patients. Furthermore, levels of acetate, a bacterially derived SCFA, were lower and positively correlated with angiogenesis markers (VEGF and VEGF-C). In aged stroke mice, transplantation of young microbiota improved stroke outcomes by promoting angiogenesis, which was facilitated by lymphatic ingrowth into the cortex. This protective effect was linked to gut microbiota-derived acetate, which enhanced lymphangiogenesis by replenishing acetyl coenzyme A. Conclusions:(a) Gut microbiota-derived acetate promotes angiogenesis post-stroke and (b) lymphatic ingrowth into the cerebral cortex was observed in post-dMCAO mice. These findings suggest that selectively promoting SCFA-producing bacteria, particularly acetate-producers, could be a promising therapeutic strategy to reduce functional impairments in older stroke subjects.
10.3389/fnins.2024.1398913
Fecal level of butyric acid, a microbiome-derived metabolite, is increased in patients with severe carotid atherosclerosis.
Scientific reports
The short-chain fatty acid (SCFA) butyric acid maintains a healthy gut barrier and vascular endothelium. We aimed to investigate the association between fecal butyric acid, carotid atherosclerosis and risk factors for ischemic stroke. Patients with severe carotid atherosclerosis (i.e. ≥ 50% stenosis) (n = 43) were compared with healthy controls (n = 38). We analyzed fecal SCFAs by gas chromatography, microbiota composition by 16S rRNA sequencing, markers of gut barrier damage and inflammasome activation by immunoassay, and plasma SCFAs by ultra-high performance liquid chromatography-tandem mass spectroscopy. Patients had higher fecal butyric acid level (p = 0.024), along with increased functional potential of microbial butyric acid production (p = 0.031), compared with controls. Dietary fiber intake was comparable. Patients had higher levels of gut barrier damage markers CCL25 and IFABP, and the inflammasome activation marker IL-18, whereas plasma level of butyric was similar. Increased fecal butyric acid was associated with higher BMI, waist-hip ratio, HbA1c, CRP and leukocyte count. Contrary to our hypothesis, patients with severe carotid atherosclerosis had higher fecal butyric acid level, and increased microbial production, compared with controls. Gut barrier damage in patients might indicate decreased absorption of butyric acid and hence contribute to the higher fecal level.
10.1038/s41598-022-26759-x
Dysbiosis of Gut Microbiota Is an Independent Risk Factor of Stroke-Associated Pneumonia: A Chinese Pilot Study.
Xia Geng-Hong,Zhang Ming-Si,Wu Qi-Heng,Wang Hui-Di,Zhou Hong-Wei,He Yan,Yin Jia
Frontiers in cellular and infection microbiology
Background and Purpose:Identifying risks of stroke-associated pneumonia (SAP) is important for clinical management. We aimed to evaluate the association between gut microbiome composition and SAP in patients with acute ischemic stroke (AIS). Methods:A prospective observational study was conducted, and 188 AIS patients were enrolled as the training cohort. Fecal and serum samples were collected at admission. SAP was diagnosed by specialized physicians, and disease severity scores were recorded. Fecal samples were subjected to 16S rRNA V4 tag sequencing and analysed with QIIME and LEfSe. Associations between the most relevant taxa and SAP were analysed and validated with an independent cohort. Fecal short-chain fatty acid (SCFA), serum D-lactate (D-LA), intestinal fatty acid-binding protein (iFABP) and lipopolysaccharide binding protein (LBP) levels were measured. Results:Overall, 52 patients (27.7%) had SAP in the training cohort. The gut microbiome differed between SAP and non-SAP patients; specifically, depletion and opportunistic pathogen enrichment were noted in SAP patients, as confirmed in the validation cohort (n=144, 28 SAP [19.4%]). Based on multivariate analysis, was identified as a protective factor against SAP in both cohorts (training, aOR 0.52; 95% CI, 0.30-0.90; validation, aOR 0.44; 95% CI, 0.23-0.85). The combination of these taxa into a microbial dysbiosis index (MDI) revealed that dysbiosis increased nearly 2 times risk of SAP (training, aOR 1.95; 95% CI, 1.19-3.20; validation, aOR 2.22; 95% CI, 1.15-4.26). Lower fecal SCFA levels and higher serum D-LA levels were observed in SAP patients. Furthermore, SAP was an independent risk factor of 30-day death and 90-day unfavorable outcome. Conclusion:We demonstrate that a microbial community with depleted and enriched opportunistic pathogens is associated with increased risk of SAP among AIS patients. Gut microbiota screening might be useful for identifying patients at high risk for SAP and provide clues for stroke treatment.
10.3389/fcimb.2021.715475
Integrative microbiomics, proteomics and lipidomics studies unraveled the preventive mechanism of Shouhui Tongbian Capsules on cerebral ischemic stroke injury.
Journal of ethnopharmacology
ETHNOPHARMACOLOGICAL RELEVANCE:Cerebral ischemic stroke (CIS) is one of the most important factors leading to death and disability, which seriously threaten the survival and health of patients. The intentional flora and its derived metabolites are demonstrated to play vital roles in the physiology and onset of CIS. Shouhui Tongbian Capsules (SHTB), a Traditional Chinese Medicine, could regulate gut microbiota and metabolites. Study has found that SHTB has protective effect on CIS, but the mechanism is still unclear. AIM OF STUDY:This study was designed to evaluate the preventive effects and the mechanism of SHTB on CIS injury. MATERIALS AND METHODS:The rats were pretreated with SHTB for 5 days, then the middle cerebral artery occlusion/reperfusion (MCAO/R) was established. Neurological deficit score, TTC staining, brain water content, H&E and Nissl staining were preformed to evaluate the preventive effects of SHTB on CIS. The Occludin and ZO-1 were analyzed to evaluate the blood-brain barrier (BBB). 16S rDNA sequencing and LC-ESI-MS/MS-based metabolomics profiling were performed to analyze the gut microbiota composition and short chain fatty acids (SCFAs) profile in gut. Serum lipopolysaccharide specific IgA antibody (LPS-SIgA) and diamine oxidase (DAO), as well as colon Claudin 5 and ZO-1 were analyzed to evaluate the intestinal barrier. Proteomics was used to evaluated the proteins profile in brain. Lipidomics were used to evaluate the brain SCFAs as well as medium and long chain fatty acids (MCFAs and LCFAs). Malondialdehyde (MDA), Total Superoxide dismutase (T-SOD), Glutathione (GSH), Glutathione peroxidase (GSH-Px), Catalase (CAT) and reactive oxygen species (ROS) were assayed to evaluate the oxidative stress in brain. Western blot was performed to evaluate the expression of PPARγ, Nrf2, SLC3A2, SCL7A11, GPX4, ACSL4 and LOX. RESULTS:SHTB prevented rats from MCAO/R injury, which was confirmed by lower cerebral infarct rate, brain water content, neurological deficit score and nissl body loss, and improved brain pathology. Meanwhile, SHTB upregulated the expression of ZO-1 and Occludin to maintain the integrity of BBB. 16S rDNA sequencing and LC-ESI-MS/MS-based targeted metabolomics found that SHTB increased the abundance of gut microbiota, regulated the numbers of intestinal bacteria to increase the production of Acetic acid, Propionic acid, and Butyric acid, as well as decrease the production of Valeric acid and Hexanoic acid in the gut. Meanwhile, SHTB improved the intestinal barrier by upregulating the protein levels of Claudin 5 and ZO-1, which was confirmed by low concentrations of LPS-SIgA and DAO in serum. Multi omics and spearman correlation analysis indicated that SHTB regulated the abundance of Escherichia-Shigella and Lactobacillus to increase Acetic acid, Propionic acid, and Butyric acid to induce the expression of PPARγ, thereby regulating fatty acid metabolism and degradation, improving lipid metabolism disorders, downregulating lipid oxidative stress, inhibiting ferroptosis, and alleviating brain injury. CONCLUSION:This study confirmed that SHTB improved the disturbance of fatty acid metabolism in brain tissue by regulating gut microbiota and the production of fecal SCFAs to inhibit ferroptosis caused by lipid oxidative stress and prevent CIS injury, which provided a potential candidate drug for the prevention of CIS.
10.1016/j.jep.2024.118874
The Association of Post-Stroke Cognitive Impairment and Gut Microbiota and its Corresponding Metabolites.
Liu Yongqiang,Kong Cheng,Gong Li,Zhang Xiaohui,Zhu Yuefei,Wang Haichao,Qu Xiao,Gao Renyuan,Yin Fang,Liu Xueyuan,Qin Huanlong
Journal of Alzheimer's disease : JAD
BACKGROUND:Post-stroke cognitive impairment (PSCI) is an important factor causing disabilities after acute ischemic stroke (AIS). Emerging evidence suggested that gut microbiota play an important role in cognitive impairment. OBJECTIVE:This study aimed to explore the association between PSCI and gut microbiota. METHOD:65 patients with newly diagnostic AIS finished the fecal collection on admission and cognitive assessment 3 months later in the clinic. Fecal samples were subjected to 16SrRNA gene sequencing and gas chromatography-mass spectrometry analysis. Additionally, we enrolled new 18 AIS patients, whose treatment was supplemented by probiotics, to assess the potential of microbial treatment in PSCI. RESULTS:PSCI patients were characterized by the significantly decreased alpha-diversity, disturbed microbial composition, and corresponding metabolites compared with non-PSCI patients. Increased Fusobacterium and deficiency of microbial metabolized short-chain fatty acids (SCFAs) were significantly associated with PSCI. A model based on gut microbiota and SCFAs could predict 3 months or longer PSCI early and accurately after stroke onset. While traditional probiotic administration had little effect on PSCI, it could ameliorate patients' mood, including depression and anxiety in the 3 months after stroke. CONCLUSION:Our study revealed the association between PSCI and gut microbiota and its corresponding metabolites for the first time, suggesting the potential for applying microbiota and its corresponding metabolites to early clinical diagnosis and treatment of PSCI.
10.3233/JAD-191066
Gut Microbiota Dysbiosis in Acute Ischemic Stroke Associated With 3-Month Unfavorable Outcome.
Frontiers in neurology
BACKGROUND:Alterations in the gut microbiota after ischemic stroke have been demonstrated, whereas the effect on stroke outcome remains to be established. METHODS:A total of 132 consecutive patients with acute ischemic stroke were prospectively enrolled. Their gut microbiomes within 24 h of admission were profiled using 16S ribosomal RNA (rRNA) gene (V3-V4 region) sequencing. Microbiota comparisons were made between groups with good outcome ( = 105) and poor outcome ( = 27) based on 3-month modified Rankin Scale scores of 0-2 and 3-6. Propensity score-matching (PSM) analysis was conducted to assess the robustness of our findings. The functional potential was predicted using the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). RESULTS:Patients in the poor outcome group were characterized by a significant reduction in the alpha diversity (Shannon index, = 0.025; Simpson index, = 0.010), an increase in the pathogenic bacteria (e.g., and ), and a decrease in the short-chain fatty acids (SCFAs)-producing bacteria (e.g., , and ) to those with good outcome group (all < 0.05). Similar results of microbial composition were obtained after PSM. The PICRUSt revealed that the pathway for membrane transport was relatively dominant in patients with poor outcome ( < 0.05). CONCLUSION:This study demonstrated that stroke patients with 3-month poor outcome had baseline gut microbiota dysbiosis featured by increased pathogenic bacteria and decreased SCFAs-producing bacteria.
10.3389/fneur.2021.799222
Gut Microbiota Ecological and Functional Modulation in Post-Stroke Recovery Patients: An Italian Study.
Microorganisms
Ischemic stroke (IS) can be caused by perturbations of the gut-brain axis. An imbalance in the gut microbiota (GM), or dysbiosis, may be linked to several IS risk factors and can influence the brain through the production of different metabolites, such as short-chain fatty acids (SCFAs), indole and derivatives. This study examines ecological changes in the GM and its metabolic activities after stroke. Fecal samples of 10 IS patients were compared to 21 healthy controls (CTRLs). GM ecological profiles were generated via 16S rRNA taxonomy as functional profiles using metabolomics analysis performed with a gas chromatograph coupled to a mass spectrometer (GC-MS). Additionally fecal zonulin, a marker of gut permeability, was measured using an enzyme-linked immuno assay (ELISA). Data were analyzed using univariate and multivariate statistical analyses and correlated with clinical features and biochemical variables using correlation and nonparametric tests. Metabolomic analyses, carried out on a subject subgroup, revealed a high concentration of fecal metabolites, such as SCFAs, in the GM of IS patients, which was corroborated by the enrichment of SCFA-producing bacterial genera such as , Christensellaceae, and . Conversely, indole and 3-methyl indole (skatole) decreased compared to a subset of six CTRLs. This study illustrates how IS might affect the gut microbial milieu and may suggest potential microbial and metabolic biomarkers of IS. Expanded populations of and enrichment of acetic acid could be considered potential disease phenotype signatures.
10.3390/microorganisms12010037
Dysbiosis of Gut Microbiota and Short-Chain Fatty Acids in Acute Ischemic Stroke and the Subsequent Risk for Poor Functional Outcomes.
Tan Chuhong,Wu Qiheng,Wang Huidi,Gao Xuxuan,Xu Ruoting,Cui Ziming,Zhu Jiajia,Zeng Xiuli,Zhou Hongwei,He Yan,Yin Jia
JPEN. Journal of parenteral and enteral nutrition
BACKGROUND:The intestinal microbiota and its metabolites have been reported to play an important role in stroke. Gut microbiota-originating short-chain fatty acids (SCFAs) modulate brain functions directly or indirectly through immune, endocrine, vagal, and other humoral pathways. However, relatively few investigations have evaluated the gut microbiome and SCFAs spectrum or their potential associations with stroke outcomes in acute ischemic stroke (AIS) patients with different stroke severities. METHODS:We used 16S rRNA gene sequencing and gas chromatography to compare the fecal microbial composition and SCFA spectrum between AIS patients (n = 140) and healthy controls (n = 92). Their associations with 90-day poor functional outcomes were evaluated by logistic regression models. RESULTS:We found that the intestinal microbiota distinguished AIS patients from healthy controls. A lack of SCFAs-producing bacteria and a low fecal SCFAs level defined dysbiosis in AIS patients, especially those with increased stroke severity. The SCFAs levels were negatively correlated with stroke severity and prognosis. Reduced SCFAs levels, especially acetate, were associated with an increased risk of 90-day poor functional outcomes even after adjustments. CONCLUSIONS:Dysbiosis of SCFAs-producing bacteria and SCFAs in AIS patients increased the subsequent risk for poor functional outcomes, indicating that SCFAs could be potential prognostic markers and therapeutic targets for stroke.
10.1002/jpen.1861
Bioinformatics Approach to Identify the Pathogenetic Link of Gut Microbiota-Derived Short-Chain Fatty Acids and Ischemic Stroke.
Molecular neurobiology
Stroke is a life-threatening condition that impairs the arteries and causes neurological impairment. The incidence of stroke is increasing year by year with the arrival of the aging population. Thus, there is an urgent need for early stroke diagnosis. Short-chain fatty acids (SCFAs) can modulate the central nervous system and directly and indirectly impact behavioral and cognitive functions. This study aimed to investigate the connection between SCFA metabolism and stroke development via bioinformatic analysis. Initially, the Gene Set Enrichment Analysis (GSEA) and immune cell infiltration analysis were performed based on RNA data from stroke patients to comprehend the mechanisms governing stroke pathogenesis. The functional analysis, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interaction (PPI), was performed based on the Differentially Expressed Gene (DEG) selected by the limma package. 1220 SCFA metabolism-related genes screened from Genecards databases were intersected with 242 genes in main modules determined by Weighted Gene Co-Expression Network Analysis (WGCNA), and the final 10 SCFA key genes were obtained. GO analysis revealed that these genes were involved in immune response processes. Through lasso regression analyses, we established a stroke early diagnosis model and selected 6 genes with diagnostic value. The genes were validated by the area under curve (AUC) values and had a relatively good diagnostic performance. Finally, 4 potential therapeutic drugs targeting these genes were predicted using the Drug Signatures Database (DSigDB) via Enrichr. In conclusion, this paper analyzes the involvement of SCFAs in the complex gut-brain axis mechanism, which contributes to developing new targets for treating central nervous system diseases and provides new ideas for early ischemic stroke diagnosis.
10.1007/s12035-024-04176-7
Gut Microbiota and Their Metabolites in Stroke: A Double-Edged Sword.
Stroke
Besides damaging the brain, stroke causes systemic changes, including to the gastrointestinal system. A growing body of evidence supports the role of the gut and its microbiota in stroke, stroke prognosis, and recovery. The gut microbiota can increase the risk of a cerebrovascular event, playing a role in the onset of stroke. Conversely, stroke can induce dysbiosis of the gut microbiota and epithelial barrier integrity. This has been proposed as a contributor to systemic infections. In this review, we describe the role of the gut microbiota, microbiome and microbiota-derived metabolites in experimental and clinical stroke, and their potential use as therapeutic targets. Fourteen clinical studies have identified 62 upregulated (eg, , ) and 29 downregulated microbial taxa (eg, ) between stroke and healthy participants. The majority found that stroke patients have reduced gut microbiome diversity. However, other nonbacterial microorganisms are yet to be studied. In experimental stroke, severity is dependent on gut microbiome composition, whereas the latter can greatly change with antibiotics, age, and diet. Consumption of foods rich in choline and L-carnitine are positively associated with stroke onset via production of trimethylamine N-oxide in experimental and clinical stroke. Conversely, in mice, consumption of dietary fiber improves stroke outcome, likely via gut microbiota-derived metabolites called short-chain fatty acids, such as acetate, propionate, and butyrate. The majority of the evidence, however, comes from experimental studies. Clinical interventions targeted at gut microbiota-derived metabolites as new therapeutic opportunities for stroke prevention and treatment are warranted.
10.1161/STROKEAHA.121.036800
The Prognostic Biomarkers of Plasma Trimethylamine N-Oxide and Short-Chain Fatty Acids for Recanalization Therapy in Acute Ischemic Stroke.
International journal of molecular sciences
Bidirectional communication of the microbiota-gut-brain axis is crucial in stroke. Recanalization therapy, namely intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT), are recommended for eligible patients with acute ischemic stroke (AIS). It remains unclear whether gut microbiota metabolites, namely trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFAs), can predict the prognosis after recanalization therapy. This prospective study recruited patients with AIS receiving IVT, EVT, or both. The National Institutes of Health Stroke Scale (NIHSS) and modified Rankin scale (mRS) scores were used to assess the severity and functional outcomes of AIS, respectively. A functional outcome of mild-to-moderate disability was defined as a mRS score of 0-3 at discharge. Plasma TMAO and SCFA levels were measured through liquid chromatography with triple-quadrupole mass spectrometry. Fifty-six adults undergoing recanalization therapy for AIS were enrolled. Results showed that TMAO levels were not associated with stroke severity and functional outcomes, while isovalerate levels (one of the SCFAs) were negatively correlated with NIHSS scores at admission and discharge. In addition, high isovalerate levels were independently associated with a decreased likelihood of severe disability. The study concluded that an elevated plasma isovalerate level was correlated with mild stroke severity and disability after recanalization therapy for AIS.
10.3390/ijms241310796
Short Chain Fatty Acids Taken at Time of Thrombectomy in Acute Ischemic Stroke Patients Are Independent of Stroke Severity But Associated With Inflammatory Markers and Worse Symptoms at Discharge.
Henry Nicholas,Frank Jacqueline,McLouth Christopher,Trout Amanda L,Morris Andrew,Chen Jianzhong,Stowe Ann M,Fraser Justin F,Pennypacker Keith
Frontiers in immunology
Introduction:Short chain fatty acids (SCFA) are gut microbiota-derived metabolites that contribute to the gut-brain axis and may impact stroke outcomes following gut dysbiosis. We evaluated plasma SCFA concentrations against stroke severity parameters and identified SCFA-associated protein networks. Methods:The Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC), a continuously enrolling tissue bank, was used to obtain stroke samples. Arterial blood distal and proximal to the thrombus was obtained from Acute Ischemic Stroke (AIS) Patients (n=53) during thrombectomy. Patient demographics, stroke presentation and outcome parameters were reported. The SCFAs were isolated from proximal plasma chemical derivatization UHPLC coupled tandem mass spectrometry using electrospray ionization and multiple reaction monitoring. Proteomic levels for 184 cardioembolic and inflammatory proteins was quantified from systemic and intracranial plasma by Olink. Arterial blood from cerebrovascular patients undergoing elective neurointerventional procedures was used as controls. Results:Acetate positively correlated with time from last known normal (LKN) and was significantly lower in stroke patients compared to control. Isobutyrate, Butyrate and 2-Methylbutyrate negatively correlated with %ΔNIHSS. Isobutyrate and 2-Methylbutyrate positively correlated with NIHSS discharge. SCFA concentrations were not associated with NIHSS admission, infarct volume, or edema volume. Multiple SCFAs positively associated with systemic and pro-inflammatory cytokines, most notably IL-6, TNF-α, VCAM1, IL-17, and MCP-1. Conclusions:Plasma SCFA concentrations taken at time of stroke are not associated with stroke severity at presentation. However, higher levels of SCFAs at the time of stroke are associated with increased markers of inflammation, less recovery from admission to discharge, and worse symptom burden at discharge.
10.3389/fimmu.2021.797302