Liu G, Tan F H-P, Lau S-Y A, Jaafar M H, Chung F Y-L, Azzam G, Liong M-T, Li Y
CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
School of Biological Sciences, Universiti Sains Malaysia, Penang, Malaysia.
J Appl Microbiol. 2022 Apr;132(4):3155-3167. doi: 10.1111/jam.14773. Epub 2021 Dec 26.
To utilize transgenic GMR-Aβ42 Drosophila melanogaster as a model to evaluate potential Alzheimer's disease (AD)-reversal effects via the administration of lactic acid bacteria (LAB) strains, and associations of LAB with changes in gut microbiota profiles.
Wild-type flies (Oregon-R) were crossed with glass multimer reporter-GAL4 (GMR-GAL4) to produce GMR-OreR (Control), while UAS-Aβ42 (#33769) were crossed with GMR-GAL4 to produce transgenic Drosophila line that expressed Aβ42 (GMR-Aβ42). Feed containing seven different LAB strains (Lactobacillus paracasei 0291, Lactobacillus helveticus 1515, Lactobacillus reuteri 30242, L. reuteri 8513d, Lactobacillus fermentum 8312, Lactobacillus casei Y, Lactobacillus sakei Probio65) were given to GMR-Aβ42 respectively, while feed without LAB strains were given to control and transgenic GMR-Aβ42.nf Drosophila lines. The morphology of the eyes was viewed with scanning electron microscopy (SEM). The changes in gut microbiota profiles associated with LAB were analysed using 16s high throughput sequencing. Malformation of eye structures in transgenic GMR-Aβ42 Drosophila were reversed upon the administration of LAB strains, with more prevalent effects from L. sakei Probio65 and L. paracasei 0291. The GMR-Aβ42.nf group showed dominance of Wolbachia in the gut, a genus that was almost absent in the normal control group (P < 0·05). The administration of L. sakei Probio65 and L. paracasei 0291 reduced the abundance of Wolbachia accompanied by increased abundance of Stenotrophomonas and Acetobacter (P < 0·05), resembling the microbial profile of the control group.
Lactobacillus sakei Probio65 and Lactobacillus paracasei 0291 have more prominent effects in reversing malformed eye of transgenic GMR-Aβ42 Drosophila, and reducing the abundance of Wolbachia accompanied by an increased abundance of Stenotrophomonas and Acetobacter.
Potentials of LAB to prevent and/or alleviate the onset and pathogenesis of neurodegenerative diseases such as AD, supporting brain health strategies along the gut-brain axis.
利用转基因GMR - Aβ42黑腹果蝇作为模型,通过给予乳酸菌(LAB)菌株来评估潜在的阿尔茨海默病(AD)逆转作用,以及LAB与肠道微生物群谱变化的关联。
野生型果蝇(俄勒冈 - R)与玻璃多聚体报告基因 - GAL4(GMR - GAL4)杂交产生GMR - OreR(对照组),而UAS - Aβ42(#33769)与GMR - GAL4杂交产生表达Aβ42的转基因果蝇品系(GMR - Aβ42)。分别给GMR - Aβ42喂食含有七种不同LAB菌株(副干酪乳杆菌0291、瑞士乳杆菌1515、罗伊氏乳杆菌30242、罗伊氏乳杆菌8513d、发酵乳杆菌8312、干酪乳杆菌Y、清酒乳杆菌Probio65)的饲料,而给对照组和转基因GMR - Aβ42.nf果蝇品系喂食不含LAB菌株的饲料。用扫描电子显微镜(SEM)观察眼睛的形态。使用16s高通量测序分析与LAB相关的肠道微生物群谱变化。给予LAB菌株后,转基因GMR - Aβ42果蝇眼睛结构的畸形得到逆转,其中清酒乳杆菌Probio65和副干酪乳杆菌0291的作用更为普遍。GMR - Aβ42.nf组肠道中沃尔巴克氏体占优势,而该菌在正常对照组中几乎不存在(P < 0.05)。给予清酒乳杆菌Probio65和副干酪乳杆菌0291可降低沃尔巴克氏体的丰度,同时增加嗜麦芽窄食单胞菌和醋酸杆菌的丰度(P < 0.05),类似于对照组的微生物谱。
清酒乳杆菌Probio65和副干酪乳杆菌0291在逆转转基因GMR - Aβ42果蝇眼睛畸形以及降低沃尔巴克氏体丰度并增加嗜麦芽窄食单胞菌和醋酸杆菌丰度方面具有更显著的作用。
LAB预防和/或缓解AD等神经退行性疾病的发病和发病机制的潜力,支持沿肠 - 脑轴的脑健康策略。