한빛사논문
- 조회1,644
Jian-Hua Mao1,†, Young-Mo Kim2,†, Yan-Xia Zhou1,3,†, Dehong Hu2, Chenhan Zhong1, Hang Chang1, Colin Brislawn2, Sasha Langley1, Yunshan Wang1,4, B. Y. Loulou Peisl5, Susan E. Celniker1, David W. Threadgill6,7, Paul Wilmes5, Galya Orr2, Thomas O. Metz2, Janet K. Jansson2,* and Antoine M. Snijders1,*
1Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. 2Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, WA, USA. 3Marine College, Shandong University, Weihai 264209, China. 4Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan 250033, Shandong, China. 5Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 7, Avenue des Hauts Fourneaux, L-4362 Esch-sur-Alzette, Luxembourg. 6Department of Veterinary Pathobiology, A&M University, College Station, Texas, USA. 7Department of Molecular and Cellular Medicine Texas, A&M University, College Station, Texas, USA.
*Correspondence
†Jian-Hua Mao, Young-Mo Kim and Yan-Xia Zhou contributed equally to this work.
Abstract
Background
Recent evidence has linked the gut microbiome to host behavior via the gut–brain axis [1,2,3]; however, the underlying mechanisms remain unexplored. Here, we determined the links between host genetics, the gut microbiome and memory using the genetically defined Collaborative Cross (CC) mouse cohort, complemented with microbiome and metabolomic analyses in conventional and germ-free (GF) mice.
Results
A genome-wide association analysis (GWAS) identified 715 of 76,080 single-nucleotide polymorphisms (SNPs) that were significantly associated with short-term memory using the passive avoidance model. The identified SNPs were enriched in genes known to be involved in learning and memory functions. By 16S rRNA gene sequencing of the gut microbial community in the same CC cohort, we identified specific microorganisms that were significantly correlated with longer latencies in our retention test, including a positive correlation with Lactobacillus. Inoculation of GF mice with individual species of Lactobacillus (L. reuteri F275, L. plantarum BDGP2 or L. brevis BDGP6) resulted in significantly improved memory compared to uninoculated or E. coli DH10B inoculated controls. Untargeted metabolomics analysis revealed significantly higher levels of several metabolites, including lactate, in the stools of Lactobacillus-colonized mice, when compared to GF control mice. Moreover, we demonstrate that dietary lactate treatment alone boosted memory in conventional mice. Mechanistically, we show that both inoculation with Lactobacillus or lactate treatment significantly increased the levels of the neurotransmitter, gamma-aminobutyric acid (GABA), in the hippocampus of the mice.
Conclusion
Together, this study provides new evidence for a link between Lactobacillus and memory and our results open possible new avenues for treating memory impairment disorders using specific gut microbial inoculants and/or metabolites.
Keywords: Collaborative Cross mouse model, Memory, Gut-brain axis, Lactobacillus, Germ-free, Metabolites, Lactate, GABA
논문정보
- Research article
- 2020년 04월 (BRIC 등록일 2020-04-21)
- 국외 연구진
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