This review examines the functional role of lactic acid bacteria (LAB) and Bifidobacteria in modulating host physiology through interconnected metabolic, immune, and neuroendocrine pathways. These effects are particularly relevant in gastrointestinal diseases, where dysbiosis is associated not only with local intestinal dysfunction but also with systemic conditions, including metabolic syndrome, infections and complications in immunocompromised individuals. LAB and Bifidobacteria play key roles through the production of short-chain fatty acids, which contribute to maintaining intestinal barrier integrity, regulating lipid and glucose metabolism, improving insulin sensitivity, and exerting anti-inflammatory effects that may reduce the risk of metabolic disorders. Beyond metabolic regulation, the review explores the emerging concept of psychobiotics, focusing on how probiotic bacteria modulate host physiology through integrated metabolic, immune and neuroendocrine mechanisms. Current evidence suggests that these effects are highly strain-specific and influenced by dosage and study design, and host-related factors, often arising indirectly through complex host-microbe interactions rather than direct neurotransmitter activity. Although increasing evidence links these microorganisms to stress regulation, mood, and cognitive function, findings from human studies remain inconsistent. Therefore, well-designed clinical trials, combined with multi-omics approaches, are needed to clarify underlying mechanisms and substantiate clinical efficacy. Overall, probiotics-based strategies offer a promising and practical approach to supporting metabolic health and general psychological well-being through functional foods.

Chronic kidney disease (CKD) is a progressive condition associated with metabolic disturbances, systemic inflammation, and the accumulation of gut-derived uremic toxins. Increasing evidence highlights the role of gut microbiota dysbiosis in the progression of CKD through the gut–kidney axis. Consequently, microbiome-targeted nutritional strategies, including probiotics, prebiotics, and synbiotics, have emerged as promising complementary approaches to modulate intestinal microbial composition and metabolic functions. This review summarizes and critically evaluates the current clinical evidence regarding the use of these interventions in CKD patients. Clinical studies indicate that supplementation with probiotics, prebiotics, and synbiotic formulations may promote beneficial shifts in the composition of the gut microbiota, enhance saccharolytic fermentation, and increase the production of short-chain fatty acids (SCFAs). These changes have been associated with reduced circulating levels of gut-derived uremic toxins such as indoxyl sulfate and p-cresyl sulfate, as well as with the attenuation of systemic inflammation and oxidative stress. However, available trials remain heterogeneous in terms of study design, probiotic strains, prebiotic substrates, dosing regimens, and patient populations, and are frequently limited by small sample sizes and short intervention durations. As a result, evidence for improvements in renal function and long-term clinical outcomes remains inconclusive. While synbiotics may offer theoretical advantages by combining microbial supplementation with targeted substrates that support microbial growth and metabolic activity, current evidence does not consistently demonstrate superior clinical efficacy. Overall, these interventions often improve surrogate biomarkers, but their effects on renal function and hard clinical outcomes remain uncertain. Larger, longer-duration multicenter randomized controlled trials with standardized formulations are needed to establish their clinical utility and to better elucidate microbiota–host interactions in CKD. Advancing this field may support the development of personalized microbiome-based therapeutic strategies aimed at modulating the gut–kidney axis and ultimately improving clinical outcomes in CKD patients.