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Chen et al. Microbiome Res Rep 2025;4:6 https://dx.doi.org/10.20517/mrr.2024.38 Page 7 of 14

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.

and sinusoids arranged in an approximate radiating pattern [Figure 4]. The model group showed a higher
incidence of hepatocellular fatty degeneration, with a small number of variably sized round vacuoles visible
within the cytoplasm. There was significant hepatocellular ballooning degeneration, characterized by a
balloon-like swelling of hepatocytes, with the nucleus being centrally located or displaced to one side, and
the cytoplasm exhibiting a sparse or fine reticular structure. The group treated with L. johnsonii CCFM1376
demonstrated a decline in hepatocellular fatty degeneration and a decline in the round vacuoles within the
cytoplasm.

L. johnsonii CCFM1376 alters the hepatic and intestinal bile acid composition in
hypercholesterolemic mice
The impact on bile acid composition represents the most direct pathway through which strains with high
BSH activity exert their effects on cholesterol metabolism. To ascertain the influence of L. johnsonii
CCFM1376 on the bile acid content in mice, this study conducted targeted quantitative measurements of
bile acids in the liver, serum, distal ileum contents, and feces of the mice. The high-cholesterol diet
significantly increased the levels of cholic acid (CA) in the livers of mice [P <0.05, Figure 5A]. In
comparison with the model group, L. johnsonii CCFM1376 significantly reduced the hepatic CA levels in
mice with hypercholesterolemia. In the serum, levels of β-muricholic acid (β-MCA), CA, chenodeoxycholic
acid (CDCA), LCA, and ursodeoxycholic acid (UDCA) in mice on a high-cholesterol diet were all
significantly higher than those in the control group. However, no considerable divergences were noted
between the L. johnsonii CCFM1376 group and the model group [P <0.05, Figure 5B]. The ileum, which is
rich in bile acids, showed a significant increase in the levels of several unconjugated bile acids, including β-
MCA, CA, CDCA, UDCA, and hyodeoxycholic acid (HDCA), in the L. johnsonii CCFM1376 group in
comparison with the model group [P < 0.05, Figure 5C]. Additionally, the levels of β-MCA, DCA, LCA,
UDCA, and HDCA in the feces exhibited a marked rise in the L. johnsonii CCFM1376 group than in the
model group [P < 0.05, Figure 5D]. Compared to the control group’s total bile acid content, the L. johnsonii
CCFM1376 group only showed a significant increase in total bile acid content in the feces, while there were
no significant changes in the total bile acid content of the liver, serum, or ileal contents. [P < 0.05, Figure 5E-
H]. In the L. johnsonii CCFM1376 group, the proportion of unconjugated bile acids in the liver, serum, ileal
contents, and feces exhibited varying degrees of change, with a notably increased proportion of
unconjugated bile acids in the ileum [Figure 5I-L]. Correspondingly, the levels of conjugated bile acids have
also changed [Figure 6].