Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, India.
Department of Bioengineering, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, India.
Physiol Behav. 2021 Jul 1;236:113411. doi: 10.1016/j.physbeh.2021.113411. Epub 2021 Mar 31.
Saccharomyces boulardii, a probiotic yeast is well prescribed for various gastrointestinal disorders accompanied by gut dysbiosis such as inflammatory bowel disease, bacterial diarrhea and antibiotic associated diarrhea. Gut dysbiosis has been associated with central nervous system via gut brain axis primarily implied in the modulation of psychiatric conditions. In the current study we use Saccharomyces boulardii as a therapeutic agent against gut dysbiosis associated cognitive decline. In mice, gut dysbiosis was induced by oral Ampicillin Na (250 mg/kg twice-daily) for 14 days. While in the treatment group S. boulardii (90 mg/kg once a day) was administered orally for 21 days along with 14 days of antibiotic treatment. Gene expression studies revealed antibiotic mediated decrease in the Lactobacillus, Bifidobacterium, Firmicutes and Clostridium which were restored by S. boulardii treatment. Cognitive behavioral studies showed a parallel reduction in fear conditioning, spatial as well as recognition memory which were reversed upon S. boulardii treatment in these animals. S. boulardii treatment reduced myeloperoxidase enzyme, an inflammatory marker, in colon as well as brain which was increased after antibiotic administration. Similarly, S. boulardii reduced the brain acetylcholine esterase, oxidative stress and inflammatory cytokines and chemokines which were altered due to antibiotic treatment. S. boulardii treatment also protected hippocampal neuronal damage and restored villus length and crypt depth thus normalizing gut permeability in antibiotic treated animals. Hence, we conclude that S. boulardii prevented antibiotic associated gut dysbiosis leading to reduced intestinal and brain inflammation and oxidative stress thus preventing hippocampal neuronal damage and eventually reversing gut dysbiosis associate cognitive decline in mice.
布拉氏酵母菌（一种益生菌酵母）常用于治疗各种伴有肠道菌群失调的胃肠道疾病，如炎症性肠病、细菌性腹泻和抗生素相关性腹泻。肠道菌群失调与中枢神经系统有关，主要通过肠脑轴调节精神疾病。在本研究中，我们使用布拉氏酵母菌作为治疗与肠道菌群失调相关认知功能下降的药物。在小鼠中，通过口服氨苄青霉素钠（250mg/kg，每日两次）诱导肠道菌群失调 14 天。而在治疗组中，每天口服布拉氏酵母菌（90mg/kg），与抗生素治疗 14 天同时进行 21 天。基因表达研究表明，抗生素介导的乳酸杆菌、双歧杆菌、厚壁菌和梭菌减少，而布拉氏酵母菌治疗可以恢复这些细菌。认知行为研究表明，在这些动物中，恐惧条件反射、空间和识别记忆平行下降，而布拉氏酵母菌治疗可以逆转这种情况。布拉氏酵母菌治疗降低了结肠和大脑中的髓过氧化物酶（一种炎症标志物），而抗生素给药后其含量增加。同样，布拉氏酵母菌降低了大脑乙酰胆碱酯酶、氧化应激和炎症细胞因子和趋化因子，这些变化是由于抗生素治疗引起的。布拉氏酵母菌治疗还保护了海马神经元损伤，恢复了绒毛长度和隐窝深度，从而使抗生素处理动物的肠道通透性正常化。因此，我们得出结论，布拉氏酵母菌预防了抗生素相关的肠道菌群失调，从而减少了肠道和大脑的炎症和氧化应激，防止了海马神经元损伤，最终逆转了与肠道菌群失调相关的认知功能下降。
