Increased abundance of Segatella copri (S. copri) within the gut microbiota is associated with systemic inflammatory diseases, including rheumatoid arthritis. Although outer-membrane vesicles (OMVs) of Gram-negative bacteria are important players in microbiota–host communication, the effect of S. copri-derived OMVs on immune cells is unknown. Macrophages engulf and eliminate foreign material and are conditioned by environmental signals to promote either homeostasis or inflammation. Thus, we aimed to explore the impact of S. copri-OMVs on human macrophages in vitro, employing THP-1 and monocyte-derived macrophage models. The uptake of DiO-labeled S. copri-OMVs into macrophages was monitored by confocal microscopy and flow cytometry. Furthermore, the effect of S. copri and S. copri-OMVs on the phenotype and cytokine secretion of naïve (M0), pro-inflammatory (M1), and anti-inflammatory (M2) macrophages was analyzed by flow cytometry and ELISA, respectively. We show that S. copri-OMVs enter human macrophages through macropinocytosis and clathrin-dependent mechanisms. S. copri-OMVs, but not the parental bacterium, induced a dose-dependent increase in the expression of M1-related surface markers in M0 and M2 macrophages and activated the secretion of large amounts of pro-inflammatory cytokines in M1 macrophages. These results highlight an important role of S. copri-OMVs in promoting pro-inflammatory macrophage responses, which might contribute to systemic inflammatory diseases.

The global prevalence of obesity continues to rise and is a significant risk factor for the onset and progression of cardiovascular diseases. Despite the development of new pharmacological therapies, novel strategies are being explored to mitigate the impact of this disease. Intermittent fasting (IF) is a nutritional intervention that has gained popularity and shows potential as an innovative approach to weight management. This study aims to compile scientific evidence on various aspects of fasting, including its physiological effects, the molecular and thermogenic mechanisms involved, and recommendations regarding nutritional strategies during the refeeding period within the eating window. We conducted a narrative review, analyzing evidence available from PubMed/MEDLINE based on studies related to intermittent fasting, thermogenesis, and their associated outcomes. Our results demonstrate the existence of three commonly used IF protocols: alternate day fasting (ADF), periodic fasting (PF), and time-restricted eating (TRE). In addition to its effects on weight loss, IF has demonstrated notable benefits for cardiovascular health, oxidative stress, and metabolic function. Moreover, the interaction between the central nervous system and brown adipose tissue provides an alternative mechanism for the molecular regulation of thermogenesis. Nutritional patterns adopted during intermittent fasting play a crucial role in optimizing outcomes, with particular emphasis on the intake of proteins, fiber, bioactive compounds, and essential fatty acids during the feeding window. In summary, current evidence indicates that intermittent fasting provides a biologically robust framework for studying energy balance and holds promise for developing targeted nutritional interventions.

Intermittent fasting (IF) has gained increasing attention as a dietary strategy to improve metabolic health and prevent cardiometabolic disorders. Accumulating evidence suggests that modulation of the gut microbiota may represent one of the mechanisms underlying the physiological benefits of IF. This review summarizes the current knowledge on the mechanisms by which IF modulates gut microbial ecology and how these changes influence host metabolic and immune functions. We examine the effects of IF on gut microbiota diversity and composition, highlighting shifts in key microbial taxa associated with metabolic regulation. In addition, we discuss how fasting-induced microbial remodeling affects microbiota-derived metabolites, including short-chain fatty acids and bile acids, which play central roles in energy homeostasis, intestinal barrier integrity, and inflammatory signaling. Increasing evidence indicates that IF interacts with circadian rhythms, influencing both microbial oscillations and host metabolic pathways that coordinate nutrient sensing and energy metabolism. Furthermore, we explore the bidirectional crosstalk between the gut microbiota and the intestinal immune system, emphasizing that fasting-driven microbial changes may modulate inflammatory responses, epithelial barrier function, and immune cell activity. Finally, we discuss nutritional strategies that may enhance the beneficial effects of IF, including the incorporation of prebiotics, dietary fiber, and probiotic supplementation, to promote microbial diversity and functional resilience. Collectively, these findings support a model in which IF acts as a key modulator of the gut microbiota–immune–metabolic axis. Future integrative studies combining gut microbiome, metabolomic, and immunological approaches are needed to better understand these interactions and optimize microbiota-targeted dietary interventions.