Department of Animal Physiology and Pharmacology, Institute of Biological Sciences, Faculty of Biology and Biotechnology, Maria Curie-Skłodowska University, Akademicka 19, PL 20-033, Lublin, Poland.
Department of Industrial and Environmental Microbiology, Institute of Biological Sciences, Faculty of Biology and Biotechnology, Maria Curie-Skłodowska University, Akademicka 19, PL 20-033, Lublin, Poland.
Psychopharmacology (Berl). 2024 Feb;241(2):327-340. doi: 10.1007/s00213-023-06489-2. Epub 2023 Nov 15.
Both animal and human studies, though limited, showed that multi-strain probiotic supplementation may reduce the number of seizures and/or seizure severity. Here, we evaluated the effect of a single strain probiotic supplementation on seizure susceptibility, antiseizure efficacy of sodium valproate, and several behavioral parameters in mice.
Lactobacillus helveticus R0052 was given orally for 28 days. Its influence on seizure thresholds was evaluated in the ivPTZ- and electrically-induced seizure tests. The effect on the antiseizure potency of valproate was assessed in the scPTZ test. We also investigated the effects of probiotic supplementation on anxiety-related behavior (in the elevated plus maze and light/dark box tests), motor coordination (in the accelerating rotarod test), neuromuscular strength (in the grip-strength test), and spontaneous locomotor activity. Serum and brain concentrations of valproate as well as cecal contents of SCFAs and lactate were determined using HPLC method.
L. helveticus R0052 significantly increased the threshold for the 6 Hz-induced psychomotor seizure. There was also a slight increase in the threshold for myoclonic and clonic seizure in the ivPTZ test. L. helveticus R0052 did not affect the threshold for tonic seizures both in the maximal electroshock- and ivPTZ-induced seizure tests. No changes in the antiseizure potency of valproate against the PTZ-induced seizures were reported. Interestingly, L. helveticus R0052 increased valproate concentration in serum, but not in the brain. Moreover, L. helveticus R0052 did not produce any significant effects on anxiety-related behavior, motor coordination, neuromuscular strength, and locomotor activity. L. helveticus R0052 supplementation resulted in increased concentrations of total SCFAs, acetate, and butyrate.
Altogether, this study shows that a single-strain probiotic - L. helveticus R0052 may decrease seizure susceptibility and this effect can be mediated, at least in part, by increased production of SCFAs. In addition, L. helveticus R0052 may affect bioavailability of valproate, which warrants further investigations.
动物和人体研究虽然有限，但表明多菌株益生菌补充剂可能减少癫痫发作的次数和/或严重程度。在这里，我们评估了单一菌株益生菌补充剂对癫痫易感性、丙戊酸钠的抗癫痫作用以及小鼠几种行为参数的影响。
连续 28 天给予瑞士乳杆菌 R0052 口服。在 ivPTZ 和电诱导的癫痫发作试验中评估其对癫痫发作阈值的影响。评估益生菌补充剂对丙戊酸钠抗癫痫作用的影响，在 scPTZ 试验中进行。我们还研究了益生菌补充剂对焦虑相关行为（高架十字迷宫和明暗箱试验）、运动协调（加速旋转棒试验）、神经肌肉力量（握力试验）和自发运动活动的影响。使用 HPLC 法测定血清和脑中丙戊酸钠的浓度以及盲肠内容物中 SCFA 和乳酸的浓度。
瑞士乳杆菌 R0052 显著增加了 6Hz 诱导的运动性癫痫发作的阈值。在 ivPTZ 试验中，也观察到肌阵挛和阵挛性癫痫发作的阈值略有增加。瑞士乳杆菌 R0052 对最大电休克和 ivPTZ 诱导的癫痫发作试验中的强直发作阈值没有影响。未报道瑞士乳杆菌 R0052 对丙戊酸钠抗 PTZ 诱导癫痫发作的抗癫痫作用有任何变化。有趣的是，瑞士乳杆菌 R0052 增加了血清中丙戊酸钠的浓度，但未增加脑内的浓度。此外，瑞士乳杆菌 R0052 对焦虑相关行为、运动协调、神经肌肉力量和运动活动没有产生任何显著影响。瑞士乳杆菌 R0052 补充剂导致总 SCFA、乙酸盐和丁酸盐的浓度增加。
总之，本研究表明，单一菌株益生菌 - 瑞士乳杆菌 R0052 可能降低癫痫易感性，这种作用至少部分可以通过增加 SCFA 的产生来介导。此外，瑞士乳杆菌 R0052 可能影响丙戊酸钠的生物利用度，这需要进一步研究。
