Search Results (2)

Background: The human gut microbiome—a diverse ecosystem of trillions of microorganisms—plays an essential 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) significantly reduce microbial diversity. Loss of keystone species like Bifidobacterium infantis (B. infantis) and Lactobacillus reuteri (L. reuteri) contributes to gut dysbiosis, which has been implicated in chronic metabolic, autoimmune, cardiovascular, and neurodegenerative conditions. Materials and 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: Multiple cohort studies have consistently reported a 40–60% reduction in microbial diversity among Western populations compared to traditional societies, particularly affecting short-chain fatty acid (SCFA)-producing bacteria. Supplementation with B. infantis is associated with a significant reduction in systemic inflammation—including a 50% decrease in C-reactive protein (CRP) and reduced tumor necrosis factor-alpha (TNF-α) levels—alongside increases in regulatory T cells and anti-inflammatory cytokines interleukin-10 (IL-10) and transforming growth factor-beta 1 (TGF-β1). L. reuteri demonstrates immunomodulatory and neurobehavioral benefits in preclinical models, while both probiotics enhance epithelial barrier integrity in a strain- and context-specific manner. In murine colitis, B. infantis increases ZO-1 expression by ~35%, and L. reuteri improves occludin and claudin-1 localization, suggesting that keystone restoration strengthens barrier function through tight-junction modulation. Conclusions: Together, these findings support keystone species restoration with B. infantis and L. reuteri as a promising adjunctive strategy to reduce systemic inflammation, reinforce gut barrier integrity, and modulate gut–brain axis (GBA) signaling, indicating translational potential in metabolic and neuroimmune disorders. Future research should emphasize personalized microbiome profiling, long-term outcomes, and transgenerational effects of early-life microbial disruption. Full article

Background: Despite advances in gene-targeted and immunotherapies, many aggressive cancers—including glioblastoma and triple-negative breast cancer—remain refractory to treatment. Mounting evidence implicates metabolic reprogramming, especially dysregulation of glucose and glutamine metabolism, as a core hallmark of tumor progression. Natural compounds with metabolic-modulatory effects have emerged as promising adjuncts in oncology. Research Question and Objectives: This review investigates the following question: How can metabolic-targeted therapies—particularly those modulating the Warburg effect and glutamine metabolism—improve cancer treatment outcomes, and what role do natural compounds play in this strategy? The objectives were to (1) evaluate the therapeutic potential of metabolic interventions targeting glucose and glutamine metabolism, (2) assess natural compounds with metabolic regulatory activity, (3) examine integration of metabolic-targeted therapies with conventional treatments, and (4) identify metabolic vulnerabilities in resistant malignancies. Methods: A qualitative systematic review (QualSR) was conducted following PRISMA guidelines. A total of 87 peer-reviewed studies published between 2000 and 2024 were included. Inclusion criteria required clearly defined mechanistic or clinical endpoints and, for clinical trials, sample sizes ≥ 30. Data extraction focused on tumor response, survival, metabolic modulation, and safety profiles. Results: Curcumin significantly reduced serum TNF-α and IL-6 (both p = 0.001) and improved antioxidant capacity (p = 0.001). EGCG downregulated ERα (p = 0.002) and upregulated tumor suppressors p53 and p21 (p = 0.001, p = 0.02). High-dose intravenous vitamin C combined with chemoradiotherapy yielded a 44.4% pathologic complete response rate in rectal cancer. Berberine suppressed Akt/mTOR signaling and glutamine transporter SLC1A5 across tumor types (q < 10⁻¹⁰). However, poor bioavailability (e.g., EGCG t½ = 3.4 ± 0.3 h) and systemic toxicity limit their standalone clinical application. Conclusions: Metabolic-targeted therapies—particularly natural compounds acting on glucose and glutamine pathways—offer a viable adjunct to standard cancer therapies. Clinical translation will require biomarker-driven patient stratification, improved delivery systems, and combination trials to optimize the therapeutic impact in treatment-resistant cancers. Full article