Global Research Landscape on Lactobacillus-Based Interventions for Hypercholesterolemia: A Bibliometric and Systematic Review of Scientific Evidence and Therapeutic Efficacy

Hypercholesterolemia, characterized by elevated serum cholesterol levels, particularly Low-Density Lipoprotein Cholesterol (LDL-C), remains a major global public health challenge and a primary modifiable risk factor for cardiovascular diseases. Despite the proven efficacy of pharmacological interventions such as statins, concerns regarding adverse effects, medication adherence, and the rising costs of long-term pharmaceutical therapy have driven increasing interest in alternative and complementary therapeutic approaches. Among these, probiotic supplementation—particularly with Lactobacillus species—has emerged as a promising non-pharmacological strategy for cholesterol management. Lactobacillus strains are hypothesized to reduce serum cholesterol through multiple mechanisms including bile salt hydrolase activity, direct cholesterol assimilation into bacterial cell membranes, conversion of cholesterol to poorly absorbed coprostanol, modulation of hepatic cholesterol metabolism genes, and reduction of systemic inflammation and oxidative stress. Over the past decade, a growing body of randomized controlled trials has investigated the cholesterol-lowering potential of various Lactobacillus species delivered through diverse formulations including pharmaceutical-grade capsules and functional fermented foods. However, the evidence base remains fragmented, with considerable variability in strain selection, dosage protocols, intervention durations, delivery vehicles, and study populations. This heterogeneity has made it challenging for clinicians, policymakers, and consumers to draw clear conclusions about the clinical efficacy, optimal dosing parameters, and practical applications of Lactobacillus supplementation for hypercholesterolemia management. Furthermore, while individual clinical trials continue to emerge, there has been limited systematic effort to map the broader intellectual landscape of this research domain, identify key contributors and collaboration networks, understand geographic patterns of research activity, or trace the thematic evolution of scientific inquiry in this field. This study aims to address these knowledge gaps through a comprehensive dual-analytical approach combining systematic review methodology with bibliometric analysis. The primary purpose is threefold: first, to systematically synthesize the clinical evidence regarding the efficacy and safety of Lactobacillus supplementation in reducing serum cholesterol levels among adults with hypercholesterolemia; second, to map the global research landscape and identify patterns in scientific productivity, collaboration networks, and thematic evolution from 2015 to 2025; and third, to integrate these clinical and bibliometric perspectives to provide actionable insights for future research directions, clinical practice guidelines, and health policy decisions. Specifically, this research will systematically identify, evaluate, and synthesize evidence from randomized controlled trials examining the effects of Lactobacillus supplementation on primary outcomes of LDL-C and Total Cholesterol, as well as secondary outcomes including HDL-C and Triglycerides. The review will employ rigorous PICO (Population, Intervention, Comparator, Outcome) criteria to ensure methodological consistency, focusing on adult populations (aged ≥18 years) with confirmed hypercholesterolemia or dyslipidemia who receive Lactobacillus supplementation in any form (single or multi-strain, delivered as capsules, powders, or fermented functional foods) compared to placebo or standard care controls. Beyond simply documenting overall effects, the review will conduct structured subgroup analyses to explore dose-response relationships (examining whether higher CFU dosages produce greater lipid reductions), duration-dependent effects (assessing whether longer intervention periods yield more substantial or sustained benefits), strain-specific efficacy patterns (comparing outcomes across different Lactobacillus species), and the influence of delivery format (pharmaceutical versus food-based vehicles) on therapeutic outcomes. In parallel, the bibliometric component will employ advanced scientometric techniques to quantitatively analyze the research output, citation patterns, author collaboration networks, institutional contributions, geographic distribution of research activity, and thematic evolution of Lactobacillus-cholesterol research over the past fifteen years. Using sophisticated analytical tools including VOSviewer for network visualization and the Bibliometrix R package for comprehensive bibliometric modeling, this component will generate logistic growth models to characterize the field's developmental trajectory, identify peak productivity periods and saturation patterns, map international collaboration networks to reveal the social structure of research communities, conduct keyword co-occurrence analyses to trace the emergence and evolution of research themes, and assess the field's maturity through measures of network density, clustering patterns, and thematic consolidation. This research is expected to produce several significant outcomes with both academic and practical value. From the systematic review component, we anticipate documenting consistent evidence of LDL-C and Total Cholesterol reduction following Lactobacillus supplementation, with effect sizes varying according to strain type, dosage level, and intervention duration. Based on preliminary literature examination, we expect to find that higher dosages (≥4 × 10⁹ CFU/day) and longer durations (≥12 weeks) will demonstrate greater efficacy compared to lower doses and shorter interventions. We anticipate identifying specific strains such as Lactocaseibacillus paracasei and Lactobacillus plantarum as particularly effective for cholesterol management. Regarding HDL-C, we expect the evidence to show either neutral effects or modest reductions, which would require careful interpretation in the context of overall lipid profile improvement and HDL functionality rather than absolute HDL-C levels. For triglycerides, based on existing literature patterns, we anticipate finding minimal effects on fasting triglyceride levels across most studies, suggesting that Lactobacillus interventions primarily target cholesterol metabolism pathways rather than triglyceride-rich lipoprotein pathways. The safety profile is expected to be highly favorable, with the synthesis anticipated to reveal no serious adverse events and minimal gastrointestinal side effects, supporting the viability of long-term probiotic use for cholesterol management. This safety evidence will be particularly valuable for positioning Lactobacillus supplementation as a suitable complementary approach for patients unable to tolerate or unwilling to use pharmaceutical interventions, or as an adjunct therapy to enhance the effects of conventional lipid-lowering medications. From the bibliometric analysis component, we expect to document substantial growth in research output with an annual growth rate exceeding 10%, reflecting increasing scientific and clinical interest in probiotic interventions for cardiovascular health. The logistic growth modeling is anticipated to reveal that the field is currently in an early-to-mid expansion phase, having not yet reached theoretical or methodological saturation, suggesting significant opportunities for future high-impact contributions. We expect to find that research activity is geographically concentrated in Asian countries, particularly China, Thailand, and South Korea, with additional contributions from European nations and Brazil, reflecting regional interests in both traditional fermented foods and modern probiotic therapeutics. International collaboration rates are anticipated to be relatively low (based on preliminary observations suggesting approximately 1.5% international co-authorship), indicating that research networks remain largely national or regional in scope, which presents substantial opportunities for expanding global research partnerships. The co-authorship network analysis is expected to reveal a collaboration structure characterized by dense, internally cohesive research clusters with limited bridging connections between groups, suggesting that while individual research teams are highly productive, cross-team knowledge exchange remains underdeveloped. This finding would highlight the potential value of fostering greater inter-cluster collaboration to enhance methodological diversity and conceptual integration. The keyword co-occurrence and thematic evolution analyses are anticipated to document a progression from basic mechanistic studies and strain characterization in earlier years (2015-2020) toward more applied clinical efficacy research and investigation of specific cardiovascular outcomes in recent years (2020-2025), potentially revealing emerging interest in personalized nutrition approaches based on individual microbiome profiles. The integration of systematic review findings with bibliometric insights will produce a uniquely comprehensive understanding of both the clinical evidence base and the research ecosystem surrounding Lactobacillus interventions for hypercholesterolemia. This dual perspective will enable identification of evidence gaps where clinical questions remain unanswered despite active research, recognition of research redundancies where similar studies are being repeatedly conducted without advancing knowledge, and strategic opportunities where emerging themes or underexplored areas present high potential for impactful future research. For clinicians and healthcare providers, this research will offer evidence-based guidance on selecting appropriate Lactobacillus strains, determining optimal dosages and intervention durations, and counseling patients about expected outcomes and safety profiles. For researchers, the bibliometric findings will illuminate promising directions for future