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. 2024 Nov 9;4(1):6.
doi: 10.20517/mrr.2024.38. eCollection 2025.

Lactobacillus johnsonii CCFM1376 improves hypercholesterolemia in mice by regulating the composition of bile acids

Kexue Chen  1   2 , Danting Dang  1   2 , Huizhen Li  1   2 , R Paul Ross  3   4 , Catherine Stanton  3   4   5 , Wei Chen  1   2   6 , Bo Yang  1   2   3
Affiliations

Lactobacillus johnsonii CCFM1376 improves hypercholesterolemia in mice by regulating the composition of bile acids

Kexue Chen et al. Microbiome Res Rep. .

Abstract

Aim: Strains with high bile salt hydrolase (BSH) activity have the potential to regulate cholesterol metabolism. This study aimed to assess the alleviating effect of Lactobacillus johnsonii (L. johnsonii) CCFM1376, a strain with high BSH activity, on mice with hypercholesterolemia and explore the mechanism of its effect through the modulation of bile acid metabolism. Methods: The BSH activity was measured using the ninhydrin method. C57BL/6J mice were given a high-cholesterol diet to induce hypercholesterolemia with simultaneous gavage of L. johnsonii CCFM1376 for 8 weeks. The biochemical parameters in the serum and liver of hypercholesterolemic mice were measured to assess the alleviating effect of L. johnsonii CCFM1376 on hypercholesterolemia. Bile acid content in the mouse liver, serum, distal ileum contents, and feces was determined using liquid chromatograph mass spectrometer (LC-MS). RNA was extracted from mouse ileum and liver, and the expression levels of relative genes implicated in bile acid metabolism were measured by quantitative real-time PCR (qPCR). Results: Compared to the model group, the group treated with L. johnsonii CCFM1376 exhibited significantly reduced levels of serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), along with a significant increase in high density lipoproteins cholesterol (HDL-C) level. Moreover, hepatic levels of TC and LDL-C in the CCFM1376 group also decreased significantly. Furthermore, the content and amount of unconjugated bile acids in the hepatic-enteric circulation of the L. johnsonii CCFM1376 group significantly increased, and the total bile acid content in the feces also significantly increased. In the L. johnsonii CCFM1376 group, the relative expression levels of ileal farnesoid X receptor (FXR) and fibroblast growth factor 15 (FGF15) were downregulated, while the relative expression level of CYP7A1 was upregulated. Conclusion: These results indicated L. johnsonii CCFM1376 improves hypercholesterolemia in mice by regulating the composition of bile acids. This provides a reference for probiotic strategy to regulate cholesterol metabolism.

Keywords: FXR; Lactobacillus johnsonii; bile acids; bile salt hydrolase.

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Conflict of interest statement

Yang B, Stanton C, and Ross RP are Editorial Board members of the journal Microbiome Research Reports, with Yang B serving as the Guest Editor of the Special Issue Lactic Acid Bacteria: Functional Characterization and Applications. While the other authors have declared that they have no conflicts of interest.

Figures

Figure 1
Figure 1
The BSH activity of L. johnsonii CCFM1376 and L. johnsonii QJSWX160M2. BSH: Bile salt hydrolase.
Figure 2
Figure 2
The effect of L. johnsonii CCFM1376 on the serum biochemical parameters of hypercholesterolemic mice. (A) TC; (B) LDL-C; (C) TG; (D) HDL-C. Groups with the same lowercase letter did not exhibit significant differences, whereas those with different letters indicated significant differences (P < 0.05). TC: Total cholesterol; LDL-C: low-density lipoprotein cholesterol; TG: triglyceride; HDL-C: high density lipoproteins cholesterol.
Figure 3
Figure 3
The effect of L. johnsonii CCFM1376 on the liver biochemical parameters of hypercholesterolemic mice. (A) TC; (B) LDL-C; (C) TG. Groups with the same lowercase letter did not exhibit significant differences, whereas those with different letters indicated significant differences (P < 0.05). TC: Total cholesterol; LDL-C: low-density lipoprotein cholesterol; TG: triglyceride.
Figure 4
Figure 4
Histopathological analysis of L. johnsonii on liver tissue in hypercholesterolemic mice. H&E staining of the liver, 200×. H&E: Hematoxylin-eosin.
Figure 5
Figure 5
The effect of L. johnsonii CCFM1376 on the bile acid composition in the enterohepatic circulation of hypercholesterolemic mice. (A) Unconjugated bile acid composition in the liver; (B) Total bile acid in the liver; (C) bile acid proportion in the liver; (D) unconjugated bile acid composition in the serum; (E) Total bile acid in the serum; (F) bile acid proportion in the serum; (G) unconjugated bile acid composition in the ileum; (H) Total bile acid in the ileum; (I) bile acid proportion in the ileum; (J) unconjugated bile acid composition in the feces; (K) Total bile acid in the feces; (L) bile acid proportion in the feces. Groups with the same lowercase letter did not exhibit significant differences, whereas those with different letters indicated significant differences (P < 0.05).
Figure 6
Figure 6
The effect of L. johnsonii CCFM1376 on the conjugated bile acid composition in the enterohepatic circulation of hypercholesterolemic mice. (A) Conjugated bile acid composition in the liver; (B) conjugated bile acid composition in the serum; (C) conjugated bile acid composition in the ileum; (D) conjugated bile acid composition in the feces. Groups with the same lowercase letter did not exhibit significant differences, whereas those with different letters indicated significant differences (P < 0.05).
Figure 7
Figure 7
The effect of L. johnsonii CCFM1376 on the FXR signaling pathway in hypercholesterolemic mice. (A) FXR in the ileum; (B) FGF15; (C) FXR in the liver; (D) SHP; (E) CYP7A1. Different letters in each group indicated significant differences (P < 0.05). FXR: Farnesoid X receptor; FGF15: fibroblast growth factor 15; SHP: small heterodimer partner.
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