Lactobacillus johnsonii DM2420 Alleviates Dyslipidemia, Remodels Gut Microbiota, and Modulates the Intestinal CD36/SREBP1 Signaling Axis.

Dyslipidemia is a core pathological manifestation of lipid metabolism disorders, and dysbiosis of gut microbiota plays a key role in its onset and progression. Building upon our previous findings on the anti-inflammatory and gut microbiota-modulating effects of Lactobacillus johnsonii DM2420, this study further investigated the regulatory effects and underlying mechanisms of this strain in high-fat diet (HFD)-induced dyslipidemia mice. In vitro, L. johnsonii DM2420 significantly inhibited the accumulation of lipids in 3T3-L1 adipocytes. In HFD-fed mice, L. johnsonii DM2420 reduced the serum levels of total cholesterol (TC), low-density lipoprotein (LDL-C) and free fatty acids (FFA), and increased the amount of high-density lipoprotein cholesterol. Furthermore, HFD -fed mice led to significant increases in the levels of TC and TG in the liver and feces, whereas intervention with L. johnsonii DM2420 significantly reduced their levels. L. johnsonii DM2420 may help restore the homeostasis of lipid metabolism because it causes a reduction in the expression of CD36 protein and SREBP1 mRNA, and a decrease in adipogenic markers. Intervention with L. johnsonii DM2420 increased the relative abundance of Adlercreutzia and Bifidobacterium, and reduced the levels of Allobaculum. Allobaculum occupied a central position within the gut microbial network, which implies that it plays a role in the progression of dyslipidemia. Collectively, this study suggests that L. johnsonii DM2420 may improve dyslipidemia through modification of the composition of intestinal microbiota and a decrease in the expression of CD36/SREBP1-related pathways. This research provides theoretical and experimental support for its potential application as a probiotic agent that targets lipid metabolism disorders.