The prevalence of neurodegenerative diseases like Alzheimer’s or Parkinson’s, and mental disorders like depression or anxiety appears higher in patients with gastrointestinal tract diseases like irritable bowel syndrome and inflammatory bowel disease. Conversely, depressed patients have higher rates of gastrointestinal disorders. Moreover, an altered microbiota, called “dysbiosis” has been reported in both neurological and intestinal diseases, which suggests strong interactions between gut microbes and their host. The emergence of the intestinal microbiota as one of major regulators of gut-brain dialogue led to establish the concept of “microbiota-gut-brain axis”. The aim of our study whether a modification of the methyl donor status (i.e. folate and cobalamin) during the fetal and perinatal periods could predispose the offspring to intestinal and neurological disorders with a modified microbiota-gut-brain dialogue. Our laboratory has developed an animal model of fetal programming by using a methyl donor deficient diet during gestation and lactation periods. Several behavioral tests were conducted in offspring at different developmental stages and results showed decreased social interactions and inversely increased symptoms of anxiety and depression. At the intestinal level, we showed a gut microbiota dysbiosis by a decrease of alpha-diversity index and altered beta-diversity. This intestinal dysbiosis produced local inflammation, putatively linked to systemic and neurological inflammation. Offspring brains showed a decreased expression of brainstem receptor 5HT1A/2A and MAOA (Monoamine-oxydase-A) RNAm involved in serotoninergic pathway. Finally, a maternal methyl donors deficiency induced an alteration of microbiota-gut-brain dialogue which is responsible of transgenerational “depressive-like” behavior through the emission of key molecular actors.