The gut microbiota is an increasingly recognized target for interventions aimed at weight management. Whether an individual's baseline gut microbial diversity conditions their responsiveness to microbiota-targeted products remains uncertain. This randomized trial evaluated whether baseline diversity was associated with clinical, microbiome, and metabolic responses to a paraprobiotic derived from Lactiplantibacillus plantarum LRCC5282 (referred to here as LP5282-P) in overweight adults.
This investigation was a 12-week, randomized, double-blind, placebo-controlled, multicenter trial that enrolled 120 overweight adults. Analyses reported in the abstract are presented for the per-protocol population. The intervention compared LP5282-P against placebo and assessed clinical anthropometric outcomes, circulating metabolic markers, fecal microbiome composition, and fecal metabolite profiles.
Across the overall per-protocol cohort, administration of LP5282-P produced no statistically significant between-group differences in the clinical outcomes reported. That is, when the full compliant sample was analyzed without stratification by baseline microbiome diversity, LP5282-P did not show efficacy signals that distinguished it from placebo for the clinical endpoints reported in the abstract.
When participants were stratified by baseline gut microbial diversity, a distinct pattern emerged. In the low-diversity subgroup, LP5282-P was associated with statistically significant reductions in body weight, body mass index (BMI), and circulating leptin levels. These clinical improvements were accompanied by measurable changes in the gut ecosystem and fecal metabolites. The observed effects support the concept that baseline microbiome state can condition host responsiveness to a paraprobiotic intervention.
In the low-diversity subgroup receiving LP5282-P, compositional shifts in the gut microbiota were reported. Notably, there were higher relative abundances of Christensenellaceae, Faecalibacterium, and Alistipes after intervention. These taxa are highlighted in the abstract as increased with LP5282-P exposure in participants who began with lower microbial diversity.
Fecal metabolite profiling in the low-diversity subgroup revealed elevated concentrations of short-chain fatty acids, specifically acetate and butyrate, following LP5282-P. The intervention also altered fecal bile acid composition. These metabolic readouts accompanied the compositional microbiome changes and clinical improvements, suggesting coordinated shifts in microbial function and host-relevant metabolic pathways in the low-diversity responders.
Within the low-diversity group, changes in the relative abundances of specific genera were correlated with clinical endpoints. The abstract reports inverse correlations between changes in Akkermansia and Eubacterium and changes in body weight, body fat mass, and leptin levels—meaning increases in these taxa were associated with reductions in weight, adiposity, and leptin in that subgroup.
By contrast, participants in the high-diversity subgroup did not exhibit a consistent pattern of response across the outcome domains evaluated. The abstract indicates the high-diversity cohort showed no reliable clinical, compositional, or metabolic response to LP5282-P in the measures reported, underscoring the heterogeneity of host–microbiome interactions and the potential importance of baseline diversity as a modifier.
The trial's results support the idea that baseline gut microbial diversity may serve as a stratification variable for microbiota-targeted interventions, including paraprobiotics. The findings imply that individuals with lower baseline diversity could be more likely to experience clinical and microbiome-mediated metabolic benefits from LP5282-P. The authors recommend further studies that integrate direct measures of microbial activity and host response to clarify the biological mechanisms that underlie the observed diversity-dependent responsiveness.
Trial registration: Clinical Research Information Service (CRIS), KCT0008119.
Keywords reported in the abstract include: Gut microbiota; Lactiplantibacillus plantarum; gut microbial diversity; obesity; paraprobiotic; randomized controlled trial.
Note: Details such as exact subgroup sizes, statistical values, dosing regimen, and full methodologic parameters were not reported in the abstract and are therefore not included here.