A Mix of Potentially Probiotic Limosilactobacillus fermentum Strains Alters the Gut Microbiota in a Dose- and Sex-Dependent Manner in Wistar Rats.

Multi-strain Limosilactobacillus (L.) fermentum is a potential probiotic with reported immunomodulatory properties. This study aimed to evaluate the composition, richness, and diversity of the gut microbiota in male and female rats after treatment with a multi-strain of L. fermentum at different doses. Thirty rats (fifteen male and fifteen female) were allocated into a control group (CTL), a group receiving L. fermentum at a dose of 10 8 CFU (Lf-10 8 ), and a group receiving L. fermentum at a dose of 10 10 CFU (Lf-10 10 ) for 13 weeks. Gut microbiota and serum cytokine levels were evaluated after L. fermentum treatment. Male CTL rats had a lower relative abundance of Bifidobacteriaceae and Prevotella and a lower alpha diversity than their female CTL counterparts ( p < 0.05). In addition, male CTL rats had a higher Firmicutes/Bacteroidetes (F/B) ratio than female CTL rats ( p < 0.05). In female rats, the administration of L. fermentum at 10 8 CFU decreased the relative abundance of Bifidobacteriaceae and Anaerobiospirillum and increased Lactobacillus ( p < 0.05). In male rats, the administration of L. fermentum at 10 10 CFU decreased the F/B ratio and increased Lachnospiraceae and the diversity of the gut microbiota ( p < 0.05). The relative abundance of Lachnospiraceae and the alpha-diversity of gut microbiota were negatively correlated with serum levels of IL1β (r = -0.44) and TNFα (r = -0.39), respectively. This study identified important changes in gut microbiota between male and female rats and showed that a lower dose of L. fermentum may have more beneficial effects on gut microbiota in females, while a higher dose may result in more beneficial effects on gut microbiota in male rats.