The Journal of Nutritional Biochemistry · May 23, 2026

Molecular pathways and clinical applications of probiotics as effective supporters of intestinal, neurologic, and cardiovascular health: A narrative review

By Vergara Nieto ÁA, Diaz AH, Millán MH et al.

This narrative review aims to synthesize current knowledge on the molecular mechanisms and clinical applications of probiotics across three major health domains: intestinal, neurologic, and cardiovascular. Intestinal health: Probiotics such as Lactobacillus rhamnosus GG and Bifidobacterium lactis BB-12 reinforce epithelial integrity via upregulation of tight-junction proteins (occludin, claudin-1), attenuate inflammation through cytokine modulation (↑IL-10, ↓TNF-α, IL-6), and restore eubiosis in conditions including IBS, constipation, and antibiotic-associated diarrhea. Neurologic health: "Psychobiotic" strains (e.g., L. rhamnosus JB-1, B. longum 1714, L. helveticus R0052 + B. longum R0175) modulate neurotransmitter synthesis (GABA, serotonin), dampen HPA-axis hyperactivity, and reduce neuroinflammation, yielding improvements in anxiety, stress resilience, cognitive function, and slowing brain-atrophy progression in MCI and Alzheimer's disease. Cardiovascular health: Meta-analyses of 30+ RCTs demonstrate that probiotic supplementation (notably L. acidophilus, L. plantarum, B. longum) lowers total and LDL cholesterol (-7 to -10 mg/dL) via bile-salt hydrolase activity, SCFA-mediated GPR signaling, direct cholesterol assimilation, and modestly reduces systolic (-2 to -4 mmHg) and diastolic blood pressure through anti-inflammatory pathways and improved endothelial function. Safety: While generally safe in healthy populations, rare adverse events (bacteremia, D-lactic acidosis, horizontal gene transfer) have been reported in immunocompromised or critically ill individuals, underscoring the need for individualized risk-benefit assessments and rigorous adverse-event surveillance. Probiotics exert strain-specific, multimechanistic benefits on gut barrier integrity, neuroendocrine signaling, and cardiometabolic regulation. To fully realize their therapeutic promise, future research must pursue large-scale, head-to-head clinical trials, integrate multiomics and precision-design approaches, and establish standardized frameworks for safety monitoring and personalized formulation.

doi.org/10.1016/j.jnutbio.2026.110424PubMed 42177952Interventions