Keystone Species Restoration: Therapeutic Effects of <em>Bifidobacterium infantis</em> and <em>Lactobacillus reuteri </em>on Metabolic Regulation and Gut-Brain Axis Signaling—A Qualitative Systematic Review (QualSR)

Background: The human gut microbiome—a diverse ecosystem of trillions of microorganisms—plays a critical role in metabolic, immune, and neurological regulation. However, modern lifestyle factors such as antibiotic overuse, cesarean delivery, reduced breastfeeding, processed and high-sodium diets, alcohol intake, smoking, and exposure to environmental toxins (e.g., glyphosate) have significantly reduced microbial diversity. Loss of keystone species like Bifidobacterium infantis and Lactobacillus reuteri contributes to gut dysbiosis, which has been implicated in chronic metabolic, autoimmune, cardiovascular, and neurodegenerative conditions. Materials &amp; Methods: This Qualitative Systematic Review (QualSR) synthesized data from over 547 studies involving human participants and standardized microbiome analysis techniques, including 16S rRNA sequencing and metagenomics. Studies were reviewed for microbial composition, immune and metabolic biomarkers, and clinical outcomes related to microbiome restoration strategies. Results: Findings reveal a 40–60% reduction in microbial diversity among Western populations compared to traditional societies, particularly affecting SCFA-producing bacteria. Supplementation with B. infantis was associated with a significant reduction in systemic inflammation—including a 50% decrease in C-reactive protein (CRP) and reduced TNF-α levels—alongside increases in regulatory T cells and anti-inflammatory cytokines (IL-10, TGF-β1). L. reuteri demonstrated additional immunomodulatory effects and neurobehavioral benefits in preclinical models. Restoration interventions led to a 30–45% increase in tight junction protein expression and a 25–50% reduction in overall inflammation, suggesting improved gut barrier function and systemic immune balance. Conclusion: Restoring gut microbiota diversity through keystone species like B. infantis and L. reuteri holds therapeutic potential for a wide range of chronic inflammatory, metabolic, and neuroimmune disorders. Strengthening gut barrier integrity and reducing systemic inflammation by up to 50% underscores the microbiome’s relevance in immunometabolic health. Future research should emphasize personalized microbiome profiling, long-term outcomes, and transgenerational effects of early-life microbial disruption.