The onset and progression of the salivary and gut microbiota, the transmission and the impact of the salivary microbiota on the development of early fecal microbial communities was herein explored. We characterized the microbiota of 82 faecal and 80 salivary samples, collected from 82 healty newborns at birth, 7, 15, 30, 90 and 180 days of life, by 16S rRNA targeted-metagenomics approach. Correlation heat-maps and co-occurrence networks were used to investigate microbial taxa relationship in saliva, gut and between the two ecosystems. In saliva microbiota, Streptococcus and Staphylococcus appeared as early commensals, dominating this ecosystem through the time, while Fusobacterium, Prevotella, Porphyromonas, Granulicatella and Veillonella were late colonizers. anaerobes as Enterobacteriace, Staphylococcus and Streptococcus, were gut microbiota pioneers, followed by the anaerobic Bifidobacterium, Veillonella, Eggerthella and Bacteroides. Streptococcus, Staphylococcus and Veillonella were shared by gut and saliva ecosystems (core microbiota). Early saliva and gut microbiota seem to evolve independently driven by local adaptation strategies, with the only exception for the oral Streptococcus and Veillonella genera, involved in gut microbiota development as seeding species. A more comprehensive knowledge of how oral microbiota may impact pathophysiological conditions of gut microbiota may open new avenues on the design of postbiotics.

‘Dysbiosis’ of the adult gut microbiota, in response to challenges such as infection, altered diet, stress, and antibiotics treatment has been recently linked to pathological alteration of brain func-tion and behavior. Moreover, gut microbiota composition constantly controls microglia matura-tion as revealed by morphological observations and gene expression analysis. However, it is un-clear whether gut microbiota influences microglia functional properties and crosstalk with neu-rons, known to shape and modulate synaptic development and function. Here, we investigated how antibiotic mediated alteration of the gut microbiota influences microglial and neuronal functions in adult mice hippocampus. Hippocampal microglia from adult mice treated with oral antibiotics exhibited increased microglia density, altered basal patrolling activity, and impaired process rearrangement in response to damage. Patch clamp recordings at CA3-CA1 synapses revealed that antibiotics treatment alters neuronal functions, reducing spontaneous postsynaptic glutamatergic currents and decreasing synaptic connectivity, without reducing dendritic spines density. The effect of dysbiosis on neuronal functions are mediated by microglia-neuron cross-talk through the CX3CL1-CX3CR1 axis, as antibiotics treatment of CX3CR1 deficient mice, mod-ulates microglia density and processes rearrangement leaving unaltered synaptic function. To-gether, our findings show that the antibiotics alteration of gut microbiota impairs synaptic effi-cacy, probably through CX3CL1-CX3CR1 signaling supporting microglia as a major player in in the gut-brain axis, and in particular in the gut microbiota-to-neuron communication pathway.