Effect of Lactobacillus postbiotic supplementation on intestinal permeability, nutrient digestibility, and gut microbial and metabolic profiles in aging cats

Aging in cats is associated with declining nutrient digestibility and increased intestinal permeability, but evidence supporting microbiome-targeted interventions in older cats remains limited. We investigated whether daily supplementation with the Lactobacillus-derived postbiotic LB fermentate HF (LBHF) affected intestinal permeability, apparent total tract digestibility, gut microbiome composition, and fecal and plasma metabolomic profiles in older cats. Twenty cats aged 7.7-13.8 years were enrolled in a blinded, placebo-controlled crossover trial comprising two 29-day treatment periods separated by a 28-day washout; 18 cats completed both periods. Intestinal permeability was the primary endpoint, while nutrient digestibility, microbiome composition, and metabolomic profiles were secondary endpoints. LBHF did not affect intestinal permeability or absorptive capacity relative to placebo, although intestinal permeability was positively associated with age. Overall nutrient digestibility was higher during LBHF treatment, with the clearest endpoint-specific evidence observed for protein digestibility. LBHF was associated with a non-significant overall increase in Shannon diversity and a reduction in the relative abundance of Streptococcus lutetiensis. The increase in Shannon diversity was significant only in cats receiving placebo followed by LBHF, indicating a treatment-sequence-dependent response. Thirty-three plasma and 29 fecal metabolites showed significantly different changes during LBHF treatment compared with placebo. Plasma metabolites generally showed more positive changes during LBHF treatment, whereas most associated fecal metabolites showed more negative changes. Sequence-stratified microbiome and metabolome responses differed substantially, suggesting possible period, treatment-order, or carryover effects. Overall, LBHF did not improve intestinal permeability but was well tolerated and improved nutrient digestibility, particularly protein digestibility, while producing modest and sequence-dependent microbiome and metabolome responses. These findings suggest that the effects of LBHF in healthy older cats may relate more strongly to digestive efficiency and host metabolic responses than to intestinal permeability.