Department of Neurology, University of Kentucky, Lexington, KY, United States.
Center for Advanced Translational Stroke Science, University of Kentucky, Lexington, KY, United States.
Front Immunol. 2022 Jan 19;12:797302. doi: 10.3389/fimmu.2021.797302. eCollection 2021.
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.
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.
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.
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.
短链脂肪酸（SCFA）是肠道微生物群衍生的代谢产物，有助于肠道-大脑轴，并可能影响肠道菌群失调后的中风结果。我们评估了血浆 SCFA 浓度与中风严重程度参数的关系，并确定了与 SCFA 相关的蛋白质网络。
Blood and Clot Thrombectomy Registry and Collaboration（BACTRAC）是一个不断招募的组织库，用于获取中风样本。在血栓切除术期间，从急性缺血性中风（AIS）患者（n=53）的血栓近端和远端获得动脉血。报告了患者的人口统计学、中风表现和结局参数。使用超高效液相色谱串联质谱联用电喷雾电离和多重反应监测对近端血浆进行化学衍生化，分离 SCFA。通过 Olink 从系统性和颅内血浆中定量测定 184 种心源性和炎症蛋白的蛋白质水平。将接受择期神经介入手术的脑血管病患者的动脉血作为对照。
醋酸盐与从最后一次正常（LKN）到现在的时间呈正相关，且在中风患者中明显低于对照组。异丁酸、丁酸和 2-甲基丁酸与%ΔNIHSS 呈负相关。异丁酸和 2-甲基丁酸与 NIHSS 出院呈正相关。SCFA 浓度与 NIHSS 入院、梗死体积或水肿体积无关。多种 SCFA 与系统性和促炎细胞因子呈正相关，尤其是 IL-6、TNF-α、VCAM1、IL-17 和 MCP-1。
中风时的血浆 SCFA 浓度与发病时的中风严重程度无关。然而，中风时较高的 SCFA 水平与炎症标志物增加、入院到出院的恢复减少以及出院时症状负担加重有关。
