SELECTION OF LACTIC ACID BACTERIAL STRAINS ABLE TO MODULATE THE HOST CENTRAL NERVOUS SYSTEM

BULACIOS, G.A.; SALAZAR, P.; POSSE DE CHAVES, E.; HEBERT, E.M.; MINAHK, C.; SAAVEDRA, L.

Congreso; LV Annual SAIB Meeting and XIV PABMB Congress; 2019

Current evidence indicatesthat modulation of the central nervous system (CNS) by the microbiome occursprimarily through neuroimmune and neuroendocrine mechanisms, often involvingthe vagus nerve. In fact, the gut-brain axis provides the intestinal bacteriaand its metabolites a way to get access to the brain, thus regulating the expressionof key effectors. Although lactic acid bacteria (LAB) represent only asmall percentage of the total gut-dwelling microorganisms, they are undoubtedlyimportant players. Pro-inflammatory cytokines are naturally upregulated in theelderly and gut microbiota undergoes changes during aging. Therefore, it hasbeen proposed that administration of probiotics may decrease the synthesis ofthese pro-inflammatory cytokines, hence reducing inflammation and oxidativestress, ameliorating the effects of senescence and the progression ofneurodegenerative diseases often associated to aging. These facts stronglysuggest that LAB may be an invaluable tool in the treatment of aging-relatedpathologies such as Alzheimer?s disease (AD), where microglia and non-parenchymalmacrophages drive the neurodegeneration via neuroinflammation. The aim of thepresent work was to assess the capacity of different LAB strains metabolites toregulate the secretion of cytokines,  inhibit acetylcholinesterase (AChE) and protectcells from the cytotoxic effects of the Aβ oligomers, key features of AD.For that purpose, murineRAW 264.7 macrophages were treated with conditioned media fromseven selected LAB strains prior to the LPS stimulation. The mRNA expressionlevels of the tumor necrosis factor alpha (TNF)-α, interferon-gamma (IFN-γ) and interleukin IL-10 were examined by RT-PCR. The results showed thatconditioned media from Lactobacillusdelbrueckii subsp lactis CRL 581and Lactobacillus reuteri CRL 1098 significantly inhibited TNF-αmRNA expression. In addition,  CRL 1098strain increased IL-10 mRNA expression level in LPS-stimulated RAW 264.7 cells. Then, all conditioned media were evaluated intheir ability to inhibit AChE from human erythrocytes (AChE-E)which constitutesa model of the isoform present in the CNS. As controls, polyphenols previouslycharacterized as efficient inhibitors of AChE as well as stronganti-inflammatory agents were used. Conditioned media from L. delbrueckii CRL 581 showed a 40% inhibition of enzymaticactivity. Finally, APP-expressing neuroblastoma cells were preincubated withconditioned media and the expression of the APP transgene was induced bybutyric acid. Results evidenced that conditioned media from L. rhamnosus A29 and Enterococcus mundtii CRL 35 protectedagainst Aβ induced neuron cytotoxicity.. These data support our ongoinginvestigations regarding the molecular mechanism of LAB interactions in the gutbrain axis.