title: Modulation of intestinal microbiota by the probiotic VSL#3 resets brain gene expression and ameliorates the age-related deficit in LTP.
abstract: The intestinal microbiota is increasingly recognized as a complex signaling network that impacts on many systems beyond the enteric system modulating, among others, cognitive functions including learning, memory and decision-making processes. This has led to the concept of a microbiota-driven gut-brain axis, reflecting a bidirectional interaction between the central nervous system and the intestine. A deficit in synaptic plasticity is one of the many changes that occurs with age. Specifically, the archetypal model of plasticity, long-term potentiation (LTP), is reduced in hippocampus of middle-aged and aged rats. Because the intestinal microbiota might change with age, we have investigated whether the age-related deficit in LTP might be attenuated by changing the composition of intestinal microbiota with VSL#3, a probiotic mixture comprising 8 Gram-positive bacterial strains. Here, we report that treatment of aged rats with VSL#3 induced a robust change in the composition of intestinal microbiota with an increase in the abundance of Actinobacteria and Bacterioidetes, which was reduced in control-treated aged rats. VSL#3 administration modulated the expression of a large group of genes in brain tissue as assessed by whole gene expression, with evidence of a change in genes that impact on inflammatory and neuronal plasticity processes. The age-related deficit in LTP was attenuated in VSL#3-treated aged rats and this was accompanied by a modest decrease in markers of microglial activation and an increase in expression of BDNF and synapsin. The data support the notion that intestinal microbiota can be manipulated to positively impact on neuronal function.
authors.affiliation: S.C. di Gastroenterologia ed Epatologia, Azienda Ospedaliera di Perugia, Perugia, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Distrutti
authors.affiliation: Trinity College Institute for Neuroscience, Department of Physiology, Trinity College, Dublin, Ireland.
authors.forename: Julie-Ann
authors.initials: JA
authors.lastname: O'Reilly
authors.affiliation: Trinity College Institute for Neuroscience, Department of Physiology, Trinity College, Dublin, Ireland.
authors.forename: Claire
authors.initials: C
authors.lastname: McDonald
authors.affiliation: Dipartimento di Medicina, Università degli Studi di Perugia, Perugia, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Cipriani
authors.affiliation: Dipartimento di Scienze Chirurgiche e Biomediche, Università degli Studi di Perugia, Perugia, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Renga
authors.affiliation: Trinity College Institute for Neuroscience, Department of Physiology, Trinity College, Dublin, Ireland.
authors.forename: Marina A
authors.initials: MA
authors.lastname: Lynch
authors.affiliation: Dipartimento di Scienze Chirurgiche e Biomediche, Università degli Studi di Perugia, Perugia, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Fiorucci
mesh_terms: D000375:Aging / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D007422:Intestines / Q000382:microbiology*; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D064307:Microbiota / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects; D019936:Probiotics / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D059467:Transcriptome / Q000187:drug effects*
chemical_list: D015415:Biomarkers