Recently, a number of studies have demonstrated the existence of a link between the emotional and cognitive centres of the brain and peripheral functions through the bi-directional interaction between the central nervous system and the enteric nervous system. Therefore, the use of bacteria as therapeutics has attracted much interest. Recent research has found that there are a variety of mechanisms by which bacteria can signal to the brain and influence several processes in relation to neurotransmission, neurogenesis, and behaviour. Data derived from both in vitro experiments and in vivo clinical trials have supported some of these new health implications. While recent molecular advancement has provided strong indications to support and justify the role of the gut microbiota on the gut–brain axis, it is still not clear whether manipulations through probiotics and prebiotics administration could be beneficial in the treatment of neurological problems. The understanding of the gut microbiota and its activities is essential for the generation of future personalized healthcare strategies. Here, we explore and summarize the potential beneficial effects of probiotics and prebiotics in the neurodevelopmental process and in the prevention and treatment of certain neurological human diseases, highlighting current and future perspectives in this topic.

BACKGROUND: During early life, dynamic gut colonization and brain development co-occur with potential cross-talk mechanisms affecting behaviour. METHODS: We used 16S rRNA gene sequencing to examine the associations between gut microbiota and neurodevelopmental outcomes assessed by the Bayley Scales of Infant Development III in 71 full-term healthy infants at 18 months of age. We hypothesized that children would differ in gut microbial diversity, enterotypes obtained by Dirichlet multinomial mixture analysis and specific taxa based on their behavioural characteristics. RESULTS: In children dichotomized by behavioural trait performance in above- and below-median groups, weighted Unifrac b-diversity exhibited significant differences in fine motor (FM) activity. Dirichlet multinomial mixture modelling identified two enterotypes strongly associated with FM outcomes. When controlling for maternal pre-gestational BMI and breastfeeding for up to 3 months, the examination of signature taxa in FM groups showed that Turicibacter and Parabacteroides were highly abundant in the below-median FM group, while Collinsella, Coprococcus, Enterococcus, Fusobacterium, Holdemanella, Propionibacterium, Roseburia, Veillonella, an unassigned genus within Veillonellaceae and, interestingly, probiotic Bifidobacterium and Lactobacillus were more abundant in the above-median FM group. CONCLUSIONS: Our results suggest an association between enterotypes and specific genera with FM activity and may represent an opportunity for probiotic interventions relevant to treatment for motor disorders.

Human gut microbiota seems to drive the interaction with host metabolism through microbial metabolites, enzymes, and bioactive compounds. These components determine the host health–disease balance. Recent metabolomics and combined metabolome–microbiome studies have helped to elucidate how these substances could differentially affect the individual host pathophysiology according to several factors and cumulative exposures, such as obesogenic xenobiotics. The present work aims to investigate and interpret newly compiled data from metabolomics and microbiota composition studies, comparing controls with patients suffering from metabolic-related diseases (diabetes, obesity, metabolic syndrome, liver and cardiovascular diseases, etc.). The results showed, first, a differential composition of the most represented genera in healthy individuals compared to patients with metabolic diseases. Second, the analysis of the metabolite counts exhibited a differential composition of bacterial genera in disease compared to health status. Third, qualitative metabolite analysis revealed relevant information about the chemical nature of metabolites related to disease and/or health status. Key microbial genera were commonly considered overrepresented in healthy individuals together with specific metabolites, e.g., Faecalibacterium and phosphatidylethanolamine; and the opposite, Escherichia and Phosphatidic Acid, which is converted into the intermediate Cytidine Diphosphate Diacylglycerol-diacylglycerol (CDP-DAG), were overrepresented in metabolic-related disease patients. However, it was not possible to associate most specific microbiota taxa and metabolites according to their increased and decreased profiles analyzed with health or disease. Interestingly, positive association of essential amino acids with the genera Bacteroides were observed in a cluster related to health, and conversely, benzene derivatives and lipidic metabolites were related to the genera Clostridium, Roseburia, Blautia, and Oscillibacter in a disease cluster. More studies are needed to elucidate the microbiota species and their corresponding metabolites that are key in promoting health or disease status. Moreover, we propose that greater attention should be paid to biliary acids and to microbiota–liver cometabolites and its detoxification enzymes and pathways.

Variation of gut microbiota in metabolic diseases seems to be related to dysbiosis induced by exposure to multiple substances called Microbiota Disrupting Chemicals (MDCs), which are present as environmental and dietary contaminants. Some recent studies have focused on elucidating the alterations of gut microbiota taxa and their metabolites as a consequence of xenobiotic exposures to find possible key targets involved in the severity of the host disease triggered. Compilation of data supporting the triad of xenobiotic-microbiota-metabolic diseases would subsequently allow such health misbalances to be prevented or treated by identifying beneficial microbe taxa that could be Next Generation Probiotics (NGPs) with metabolic enzymes for MDC neutralisation and mitigation strategies. In this review, we aim to compile the available information and reports focused on variations of the main gut microbiota taxa in metabolic diseases associated with xenobiotic exposure and related microbial metabolite profiles impacting the host health status. We performed an extensive literature search using SCOPUS, Web of Science, and PubMed databases. The data retrieval and thorough analyses highlight the need for more combined metagenomic and metabolomic studies revealing signatures for xenobiotics and triggered metabolic diseases. Moreover, metabolome and microbiome compositional taxa analyses allow further exploration of how to target beneficial NGP candidates according to their alleged variability abundance and potential therapeutic significance. Furthermore, this holistic approach has identified limitations and the need of future directions to expand and integrate key knowledge to design appropriate clinical and interventional studies with NGPs. Apart from human health, the beneficial microbes and metabolites identified could also be proposed for various applications under One Health, such as probiotics for animals, plants and environmental bioremediation.

Exposure to plasticiser xenobiotics such as BPA has emerged as a significant health challenge due to globalised and industrial packaged food production. Toxicological approaches in animal models have revealed complex effects, using variable doses of BPA, on reproduction, development, obesity, immune function, metabolic and systemic toxicity. Besides, gut microbiota has emerged as a key player in regulating the impact of xenobiotic exposure on host metabolism. The effect that BPA may exert on the gut microbiota and its consequences for the host's health remains unclear. Exposure to BPA during the perinatal period requires special attention and prevention approaches since it is a particularly vulnerable period and highly implicated in the metabolic health of childhood and adulthood. The aim of this study was to assess the effects of the BPA administration during the perinatal period on promoting obesity phenotypes, altering the composition of the gut microbiota and neurocognitive development of the offspring in a murine model. In this study, pregnant mice and their offspring were administered BPA, and the increase in weight and fat accumulation, the gut microbiota composition, and the cognitive development of the offspring were analyzed. In addition, a high-fat diet (HFD) was given to the mice to test for the synergistic obesogenic effect of BPA. Our results demonstrated that BPA exposure impaired the natural remodelling of the gut microbiota during pregnancy. For instance, Akkermansia and Prevotellaceae decreased during natural remodelling of the gut microbiota during pregnancy, but they did not change in the BPA-exposed pregnant mice. Conversely, several members of the Dubosiella genus increased during normal pregnancy but not in BPA-exposed pregnant mice. Moreover, BPA exposure and HFD differentially affect gut microbial transfer from mothers to offspring and both synergistically impact the gut microbiota's establishment in the offspring. Perinatal BPA exposure imprinted changes during colonisation and maturation process of the offspring gut microbiota, identifying Lactobacillus, Eubacterium and Acetatifactor as signature genera enriched in BPA and BPA-exposed mice fed with HFD, taxa involved in a more efficient at energy harvesting from the diet. Moreover, perinatal BPA exposure seemed to alter fat and lean percentages and triggered Muribaculacea taxa imbalance that appears to be associated with disrupted activity, spatial learning, and memory, mimicking impulsivity and hyperactivity-like behavior in the offspring. In conclusion, BPA exposure and HFD exert an influence on the vertical transfer of gut microbiota from mothers to offspring and drive towards an altered establishment of gut microbiota taxa in early life, contributing to enhancing susceptibility to obesity and behavioural disorders.