Lactobacillus rhamnosus GG ameliorates atherosclerosis via suppression of oxidative stress and inflammation by reshaping the gut microbiota

Abstract

Objective

With growing awareness of probiotics' benefits, more studies are exploring their efficacy and mechanisms in reducing atherosclerosis (AS). This study aimed to investigate the potential therapeutic effects of Lactobacillus rhamnosus GG (LGG) on atherosclerotic mice and underlying mechanisms.

Design

ApoE^−/− mice were gavaged with a dose of 2 × 10⁹ CFU LGG per mouse once daily, while both ApoE^−/− and C57BL/6J mice received normal saline as controls. After 15 weeks, en face Oil Red O staining and aortic sinus morphometry were used to assess the effects of LGG intervention on AS. The expression of the Nrf2/HO-1 pathway, along with oxidative stress and inflammation, was measured in the aortic sinus, aortas, or plasma. Immune cells were analyzed by flow cytometry. 16S rRNA gene sequencing analysis evaluated structural changes in the intestinal microbiota.

Results

LGG-treated ApoE^−/− mice showed a significant reduction of AS progression by suppressing oxidative stress and inflammation. Mechanistically, LGG intervention significantly increased the levels of Nrf2/HO-1 in the aortic sinus of ApoE^−/− mice. Moreover, decreased aortic macrophages and elevated blood regulatory T cells (Tregs) were found with LGG intervention in the murine AS model. Moreover, compared to C57BL/6J mice, ApoE^−/− mice exhibited disrupted intestinal flora. Nonetheless, LGG intervention restored their intestinal flora to a composition resembling that of C57BL/6J mice, thereby increasing the abundance of beneficial bacteria.

Conclusion

LGG significantly attenuates AS by reducing oxidative stress and inflammation probably via activating the Nrf2/HO-1 pathway. Remarkably, LGG modulates gut microbiota, further enhancing its protective efficacy against AS.