Gut microbial diversity at baseline conditions the clinical, microbiome, and metabolic response to paraprobiotic Lactiplantibacillus plantarum LRCC5282 in overweight adults.
Baseline gut microbial diversity conditions responsiveness to paraprobiotic LP5282-P, with significant clinical, microbiome, and metabolic benefits observed in overweight adults with low baseline diversity but not in those with high baseline diversity.
Key Findings
Results
LP5282-P produced no significant between-group differences in any clinical outcome across the overall per-protocol population in the 12-week trial.
Study was a 12-week, randomized, double-blind, placebo-controlled, multicenter trial
120 overweight adults were enrolled
No significant between-group differences were found in any clinical outcome when analyzing the full per-protocol population
The intervention was a paraprobiotic (heat-killed/inactivated) derived from Lactiplantibacillus plantarum LRCC5282
Results
In the low-diversity subgroup, LP5282-P was associated with significant reductions in body weight, body mass index, and circulating leptin levels.
Subgroup stratification was based on baseline gut microbial diversity
Significant reductions were observed specifically for body weight, BMI, and leptin in the low-diversity subgroup receiving LP5282-P
The high-diversity subgroup exhibited no consistent response across the outcome domains examined
These findings suggest baseline diversity functioned as a stratification variable determining treatment responsiveness
Results
LP5282-P treatment in the low-diversity subgroup was accompanied by compositional shifts in the gut microbiota, including higher relative abundances of Christensenellaceae, Faecalibacterium, and Alistipes.
Gut microbiota compositional shifts were observed specifically in the low-diversity subgroup
Higher relative abundances of Christensenellaceae, Faecalibacterium, and Alistipes were noted
These taxa are generally associated with metabolic health and gut homeostasis
No consistent microbiota compositional response was reported in the high-diversity subgroup
Results
Fecal metabolite profiles in the low-diversity subgroup showed elevated acetate and butyrate concentrations and altered bile acid composition following LP5282-P intervention.
Short-chain fatty acids acetate and butyrate were elevated in the low-diversity subgroup receiving LP5282-P
Bile acid composition was also altered in this subgroup
These metabolic changes co-occurred with the clinical improvements in body weight, BMI, and leptin
Metabolite profiling of fecal samples was used to assess these changes
Results
Within the low-diversity subgroup, changes in the relative abundances of Akkermansia and Eubacterium were inversely correlated with changes in body weight, body fat mass, and leptin levels.
Inverse correlations were found between Akkermansia and Eubacterium abundance changes and changes in body weight
Inverse correlations were also observed with body fat mass and leptin levels
These correlations were specific to the low-diversity subgroup
Akkermansia and Eubacterium are taxa previously associated with metabolic health outcomes
Conclusions
Baseline gut microbial diversity was associated with differential responsiveness to LP5282-P, supporting its potential use as a stratification variable in future microbiota-targeted intervention trials.
Low-diversity individuals showed clinical, microbiome, and metabolic responses to LP5282-P
High-diversity individuals showed no consistent response across any outcome domain
Authors suggest baseline diversity could serve as a stratification variable in future trials
Trial was registered in the Clinical Research Information Service (CRIS), KCT0008119
What This Means
This research suggests that the effectiveness of a probiotic-derived supplement (a 'paraprobiotic,' meaning heat-killed bacterial cells) depends heavily on the diversity of bacteria already living in a person's gut. In a 12-week clinical trial of 120 overweight adults, the supplement—made from Lactiplantibacillus plantarum LRCC5282—showed no overall benefit when all participants were analyzed together. However, when participants were divided based on the diversity of their gut microbiome at the start of the study, a clear pattern emerged: those who began with lower gut microbial diversity experienced meaningful reductions in body weight, BMI, and leptin (a hormone linked to fat storage and appetite), while those with higher initial diversity saw no such benefits.
In the low-diversity group, the supplement also appeared to reshape the gut microbiome itself, increasing the presence of bacteria associated with metabolic health (such as Faecalibacterium and Akkermansia) and raising levels of beneficial compounds like butyrate and acetate—short-chain fatty acids produced by gut bacteria that support intestinal and metabolic health. Changes in certain bacterial species were inversely linked to changes in body weight and fat, suggesting these microbiome shifts may help explain the observed clinical improvements.
This research suggests that 'one-size-fits-all' approaches to probiotic or microbiome-targeted supplements may overlook important individual differences. People with less diverse gut microbiomes at the outset may be more likely to benefit from such interventions. If confirmed in future studies, measuring gut microbial diversity before starting a supplement could help identify who is most likely to respond, enabling more personalized approaches to weight management.
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Lim A, Kim S, Kwak W, Shim H, Kwak J, Yoon S. (2026). Gut microbial diversity at baseline conditions the clinical, microbiome, and metabolic response to paraprobiotic Lactiplantibacillus plantarum LRCC5282 in overweight adults.. Gut microbes. https://doi.org/10.1080/19490976.2026.2722835