Limosilactobacillus fermentum ACA-DC 179 oral administration attenuates atherosclerosis progression in apolipoprotein E-deficient mice through murine gut microbiota modulation

Recent research findings have established a close relationship between gut microbiota and atherosclerosis development; hence, focus has shifted towards modifying gut microbiota through probiotics administration. We thereby investigated the impact of Limosilactobacillus fermentum ACA-DC 179 on the progression of atherosclerosis in apolipoprotein E deficient (ApoE-/-) mice. Twelve-week-old ApoE-/- male and female mice were treated with low (106 CFU/mouse) or high (109 CFU/mouse) dose of L. fermentum ACA-DC 179 daily for 8 weeks. Microbiota of faeces during intervention and of gut content at study end was determined using classical microbiological and metataxonomic analyses. Additionally, blood serum biochemical markers and atherosclerotic lesions were evaluated in all animal groups. Classical microbiological analysis revealed high counts of Lactobacillus spp., Bifidobacterium spp. and Clostridium spp. for both male and female animals, regardless the treatment; however, at study end, L. fermentum ACA-DC 179 high dose managed to significantly increase Lactobacillus spp. counts of faeces of male mice. Metataxonomic analysis of faeces and gut content revealed significant differences among animal groups regarding either intestinal compartment, namely jejunum, ileum or colon, or probiotic treatment. A decrease in Lachnoclostridium and an increase in Erysipelatoclostridium were observed in faecal samples following probiotic treatment. Notably, this effect was consistent with the results obtained for all gut compartment samples of mice receiving the high dose of L. fermentum ACA-DC 179. Concerning main metabolism-related blood biomarkers, triglycerides decreased in animal groups of both sexes receiving L. fermentum ACA-DC 179. Moreover, L. fermentum ACA-DC 179 high dose significantly reduced atherosclerotic lesions in both male and female mice. Overall, our findings indicate that L. fermentum ACA-DC 179 administration attenuated the development of atherosclerosis in ApoE-/- mice supporting its beneficial potential in relevant human studies. Altered gut microbiota seems to play a significant role to this phenomenon and further studies should be conducted to elucidate underlying mechanisms.