Key Stratification of Microbiota Taxa and Metabolites in the Host Metabolic Health-Disease Balance.

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.

Exploring Next Generation Probiotics for Metabolic and Microbiota Dysbiosis Linked to Xenobiotic Exposure: Holistic Approach.

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.

Incorporating the Gut Microbiome in the Risk Assessment of Xenobiotics and Identifying Beneficial Components for One Health.

Three areas of relevance to the gut microbiome in the context of One Health were explored; the incorporation of the microbiome in food safety risk assessment of xenobiotics; the identification and application of beneficial microbial components to various areas under One Health, and; specifically, in the context of antimicrobial resistance. Although challenging, focusing on the microbiota resilience, function and active components is critical for advancing the incorporation of microbiome data in the risk assessment of xenobiotics. Moreover, the human microbiota may be a promising source of beneficial components, with the potential to metabolize xenobiotics. These may have possible applications in several areas, e.g., in animals or plants for detoxification or in the environment for biodegradation. This approach would be of particular interest for antimicrobials, with the potential to ameliorate antimicrobial resistance development. Finally, the concept of resistance to xenobiotics in the context of the gut microbiome may deserve further investigation.

Impact of Cumulative Environmental and Dietary Xenobiotics on Human Microbiota: Risk Assessment for One Health.

Chemical risk assessment in the context of the risk analysis framework was initially designed to evaluate the impact of hazardous substances or xenobiotics on human health. As the need of multiple stressors assessment was revealed to be more reliable regarding the occurrence and severity of the adverse effects in the exposed organisms, the cumulative risk assessment started to be the recommended approach. As toxicant mixtures and their "cocktail effects" are considered to be main hazards, the most important exposure for these xenobiotics would be of dietary and environmental origin. In fact, even a more holistic prism should currently be considered. In this sense, the definition of One Health refers to simultaneous actions for improving human, animal, and environmental health through transdisciplinary cooperation. Global policies necessitate going beyond the classical risk assessment for guaranteeing human health through actions and implementation of the One Health approach. In this context, a new perspective is proposed for the integration of microbiome biomarkers and next generation probiotics potentially impacting and modulating not only human health, but plant, animal health, and the environment.

Culturing and Molecular Approaches for Identifying Microbiota Taxa Impacting Children's Obesogenic Phenotypes Related to Xenobiotic Dietary Exposure.

Integrated data from molecular and improved culturomics studies might offer holistic insights on gut microbiome dysbiosis triggered by xenobiotics, such as obesity and metabolic disorders. Bisphenol A (BPA), a dietary xenobiotic obesogen, was chosen for a directed culturing approach using microbiota specimens from 46 children with obesity and normal-weight profiles. In parallel, a complementary molecular analysis was carried out to estimate the BPA metabolising capacities. Firstly, catalogues of 237 BPA directed-cultured microorganisms were isolated using five selected media and several BPA treatments and conditions. Taxa from Firmicutes, Proteobacteria, and Actinobacteria were the most abundant in normal-weight and overweight/obese children, with species belonging to the genera Enterococcus, Escherichia, Staphylococcus, Bacillus, and Clostridium. Secondly, the representative isolated taxa from normal-weight vs. overweight/obese were grouped as BPA biodegrader, tolerant, or resistant bacteria, according to the presence of genes encoding BPA enzymes in their whole genome sequences. Remarkably, the presence of sporobiota and concretely Bacillus spp. showed the higher BPA biodegradation potential in overweight/obese group compared to normal-weight, which could drive a relevant role in obesity and metabolic dysbiosis triggered by these xenobiotics.

Antimicrobial Effects of Potential Probiotics of Bacillus spp. Isolated from Human Microbiota: In Vitro and In Silico Methods.

The variable taxa components of human gut microbiota seem to have an enormous biotechnological potential that is not yet well explored. To investigate the usefulness and applications of its biocompounds and/or bioactive substances would have a dual impact, allowing us to better understand the ecology of these microbiota consortia and to obtain resources for extended uses. Our research team has obtained a catalogue of isolated and typified strains from microbiota showing resistance to dietary contaminants and obesogens. Special attention was paid to cultivable Bacillus species as potential next-generation probiotics (NGP) together with their antimicrobial production and ecological impacts. The objective of the present work focused on bioinformatic genome data mining and phenotypic analyses for antimicrobial production. In silico methods were applied over the phylogenetically closest type strain genomes of the microbiota Bacillus spp. isolates and standardized antimicrobial production procedures were used. The main results showed partial and complete gene identification and presence of polyketide (PK) clusters on the whole genome sequences (WGS) analysed. Moreover, specific antimicrobial effects against B. cereus, B. circulans, Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, Serratia marcescens, Klebsiella spp., Pseudomonas spp., and Salmonella spp. confirmed their capacity of antimicrobial production. In conclusion, Bacillus strains isolated from human gut microbiota and taxonomic group, resistant to Bisphenols as xenobiotics type endocrine disruptors, showed parallel PKS biosynthesis and a phenotypic antimicrobial effect. This could modulate the composition of human gut microbiota and therefore its functionalities, becoming a predominant group when high contaminant exposure conditions are present.

Next Generation Probiotics for Neutralizing Obesogenic Effects: Taxa Culturing Searching Strategies.

The combination of diet, lifestyle, and the exposure to food obesogens categorized into "microbiota disrupting chemicals" (MDC) could determine obesogenic-related dysbiosis and modify the microbiota diversity that impacts on individual health-disease balances, inducing altered pathogenesis phenotypes. Specific, complementary, and combined treatments are needed to face these altered microbial patterns and the specific misbalances triggered. In this sense, searching for next-generation beneficial microbes or next-generation probiotics (NGP) by microbiota culturing, and focusing on their demonstrated, extensive scope and well-defined functions could contribute to counteracting and repairing the effects of obesogens. Therefore, this review presents a perspective through compiling information and key strategies for directed searching and culturing of NGP that could be administered for obesity and endocrine-related dysbiosis by (i) observing the differential abundance of specific microbiota taxa in obesity-related patients and analyzing their functional roles, (ii) developing microbiota-directed strategies for culturing these taxa groups, and (iii) applying the successful compiled criteria from recent NGP clinical studies. New isolated or cultivable microorganisms from healthy gut microbiota specifically related to obesogens' neutralization effects might be used as an NGP single strain or in consortia, both presenting functions and the ability to palliate metabolic-related disorders. Identification of holistic approaches for searching and using potential NGP, key aspects, the bias, gaps, and proposals of solutions are also considered in this review.

Representative Bacillus sp. AM1 from Gut Microbiota Harbor Versatile Molecular Pathways for Bisphenol A Biodegradation.

Human gut microbiota harbors numerous microbial species with molecular enzymatic potential that impact on the eubiosis/dysbiosis and health/disease balances. Microbiota species isolation and description of their specific molecular features remain largely unexplored. In the present study, we focused on the cultivation and selection of species able to tolerate or biodegrade the endocrine disruptor bisphenol A (BPA), a xenobiotic extensively found in food plastic containers. Chemical xenobiotic addition methods for the directed isolation, culturing, Whole Genome Sequencing (WGS), phylogenomic identification, and specific gene-encoding searches have been applied to isolate microorganisms, assess their BPA metabolization potential, and describe encoded catabolic pathways. BPA-tolerant strains were isolated from 30% of infant fecal microbial culture libraries analyzed. Most isolated strains were phylogenetically related to the operational taxonomic group Bacillus amyloliquefaciens spp. Importantly, WGS analysis of microbial representative strain, Bacillus sp. AM1 identified the four complete molecular pathways involved on BPA degradation indicating its versatility and high potential to degrade BPA. Pathways for Exopolysaccharide (EPS) and Polyhydroxyalkanates (PHA) biopolymer synthesis were also identified and phenotypically confirmed by transmission electronic microscopy (TEM). These microbial biopolymers could generally contribute to capture and/or deposit xenobiotics.