Multi-omics gut microbiome signatures in obese women: role of diet and uncontrolled eating behaviors - metatranscriptomics

Background: obesity and related co-morbidities represent a major health challenge nowadays, with a rapidly increasing incidence worldwide. The gut microbiome has recently emerged as a key modifier of human health that can affect the development and progression of obesity, largely due to its involvement in the regulation of food intake and metabolism. However, there are still few studies that have in-depth explored the functionality of the human gut microbiome in obesity, and even fewer that have examined its relationship to eating behaviors.Methods: we thoroughly characterized the gut microbiome signatures of obesity in a well-phenotyped Italian female cohort from the NeuroFAST and MyNewGut EU FP7 projects. Fecal samples were collected from 63 overweight/obese and 37 normal-weight women, and analyzed via a multi-omics approach combining 16S rRNA amplicon sequencing, metagenomics, metatrancriptomics and lipidomics. Associations with anthropometric, clinical, biochemical and nutritional data were then sought, with particular attention to cognitive and behavioral domains of eating.Results: we identified four distinct compositional clusters of the gut microbiome in our cohort, three of which were prevalent in obese women and differently associated with eating habits and behaviors. These clusters also differed in functional features, i.e., transcriptional activity and fecal metabolites. In particular, obese women with high uncontrolled eating behavior were mostly characterized by low-diversity microbial steady state, with few and poorly interconnected species (e.g., Ruminococcus torques and Bifidobacterium spp.), which exhibited low transcriptional activity, especially of genes involved in secondary bile acid biosynthesis and neuroendocrine signaling (i.e., production of neurotransmitters, indoles and ligands for cannabinoid receptors). Consistently, high amounts of primary bile acids as well as sterols were found in their feces.Conclusions: by finding peculiar gut microbiome profiles associated with eating patterns, we have laid the foundation for elucidating gut-brain axis communication in the obese phenotype characterization. Our associative study could guide the design of microbiome-based precision interventions, aimed at rewiring microbial networks to support a healthy diet-microbiome-gut-brain axis, thus counteracting obesity and related complications.