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Psychological stress during early development and adolescence may increase the risk of psychiatric and cardiometabolic comorbidities in adulthood. The gut microbiota has been associated with mental health problems such as depression and anxiety and with cardiometabolic disease, but the potential role of the gut microbiota in their comorbidity is not well understood. We investigated the effects and mode of action of the intestinal bacterium Christensenella minuta DSM 32891 on stress-induced mental health and cardiometabolic disturbances in a mouse model of social defeat stress. We demonstrate that administered C. minuta alleviates chronic stress-induced depressive, anxiogenic and antisocial behavior. These effects are attributed to the bacterium’s ability to modulate the hypothalamic-pituitary-adrenal axis, which mediates the stress response. This included the oversecretion of corticosterone and the overexpression of its receptors, as well as the metabolism of dopamine (DA) and the expression of its receptors (D1, D2L and D2S). Additionally, C. minuta administration reduced chronically induced inflammation in plasma, spleen and some brain areas, which likely contribute to the recovery of physical and behavioral function. Furthermore, C. minuta administration prevented chronic stress-induced cardiovascular damage by regulating key enzymes mediating liver fibrosis and oxidative stress. Finally, C. minuta increased the abundance of bacteria associated with mental health. Overall, our study highlights the potential of microbiota-directed interventions to alleviate both the physical and mental effects of chronic stress.

Vancomycin-resistant Enterococcus (VRE) represents a major threat for patients’ health. Here, using a mouse model, the authors show that specific commensals restrict VRE gut colonization through depletion of fructose, a nutrient source that boosts VRE growth in vivo.

Many plasmids can be transferred between bacterial cells via conjugation; however, the mechanisms underlying the transfer of non-conjugative plasmids are less clear. Here, Humphrey et al. show that staphylococcal phages and a family of pathogenicity islands (PICIs) can mediate intra- and inter-species plasmid transfer via generalised transduction.

Objective: Although oral methotrexate (MTX) remains the anchor drug for rheumatoid arthritis (RA), up to 50% of patients do not achieve a clinically adequate outcome. In addition, there is a lack of prognostic tools for treatment response prior to drug initiation. This study was undertaken to investigate whether interindividual differences in the human gut microbiome can aid in the prediction of MTX efficacy in new‐onset RA. Methods: We performed 16S ribosomal RNA gene and shotgun metagenomic sequencing on the baseline gut microbiomes of drug‐naive patients with new‐onset RA (n = 26). Results were validated in an additional independent cohort (n = 21). To gain insight into potential microbial mechanisms, we conducted ex vivo experiments coupled with metabolomics analysis to evaluate the association between microbiome‐driven MTX depletion and clinical response. Results: Our analysis revealed significant associations of the abundance of gut bacterial taxa and their genes with future clinical response (q < 0.05), including orthologs related to purine and MTX metabolism. Machine learning techniques were applied to the metagenomic data, resulting in a microbiome‐based model that predicted lack of response to MTX in an independent group of patients. Finally, MTX levels remaining after ex vivo incubation with distal gut samples from pretreatment RA patients significantly correlated with the magnitude of future clinical response, suggesting a possible direct effect of the gut microbiome on MTX metabolism and treatment outcomes. Conclusion: Taken together, these findings are the first step toward predicting lack of response to oral MTX in patients with new‐onset RA and support the value of the gut microbiome as a possible prognostic tool and as a potential target in RA therapeutics. [ABSTRACT FROM AUTHOR]