Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada/Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Mult Scler. 2020 Oct;26(11):1340-1350. doi: 10.1177/1352458519863133. Epub 2019 Jul 18.
Recent evidence suggests a role for the gut-brain axis in the pathophysiology of multiple sclerosis (MS).
We studied biomarkers of intestinal permeability in 126 people with MS (57 relapsing-remitting multiple sclerosis (RRMS) and 69 progressive MS) and in a group of healthy controls for comparison. Serum/plasma concentrations of zonulin (a regulator of enterocyte tight junctions), tight junction proteins (ZO-1 and occludin), intestinal fatty acid binding protein (IFABP)/ileal bile acid binding protein (IBABP), D-lactate, and lipopolysaccharide (LPS) binding protein were measured.
Zonulin concentrations were significantly higher when a concurrent magnetic resonance imaging (MRI) confirmed the presence of blood-brain barrier (BBB) disruption (Gad+ RRMS) and were correlated with tight junction proteins. IBABP and D-lactate were elevated in people with RRMS compared to controls, but did not discriminate between Gad+ and Gad- subgroups. Baseline zonulin concentrations were associated with 1-year disease progression in progressive MS.
People with MS have altered biomarkers of intestinal barrier integrity. Zonulin concentrations are associated with 1-year disease progression in progressive MS and closely mirror BBB breakdown in RRMS. Zonulin may mediate breakdown of both the intestinal barrier and the BBB in gut dysbiosis through the regulation of tight junctions. This could explain how the gut-brain axis modulates neuroinflammation in MS.
最近的证据表明，肠道-大脑轴在多发性硬化症（MS）的病理生理学中起作用。
我们研究了 126 名 MS 患者（57 名复发缓解型多发性硬化症（RRMS）和 69 名进展型 MS）和一组健康对照组的肠道通透性生物标志物。测量了血清/血浆中紧密连接蛋白（ZO-1 和闭合蛋白）、肠脂肪酸结合蛋白（IFABP）/回肠胆汁酸结合蛋白（IBABP）、D-乳酸和脂多糖（LPS）结合蛋白的浓度。
当同时进行磁共振成像（MRI）证实血脑屏障（BBB）破坏（Gad+ RRMS）时，紧密连接蛋白的浓度显著升高，并与紧密连接蛋白相关。与对照组相比，RRMS 患者的 IBABP 和 D-乳酸水平升高，但不能区分 Gad+和 Gad-亚组。基线时的紧密连接蛋白浓度与进展型 MS 的 1 年疾病进展相关。
MS 患者的肠道屏障完整性的生物标志物发生了改变。在进展型 MS 中，紧密连接蛋白浓度与 1 年疾病进展相关，并且与 RRMS 中的 BBB 破坏密切相关。紧密连接蛋白可能通过调节紧密连接介导肠道屏障和 BBB 在肠道菌群失调中的破坏。这可以解释肠道-大脑轴如何调节 MS 中的神经炎症。
