Title : Lactobacillus acidophilus modulates the gut microbiota and ameliorates features of MASLD in an obese diabetic mouse model
Abstract:
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes (T2D) are among the most prevalent metabolic disorders worldwide. Increasing evidence suggests that alterations in the gut microbiota are key contributors to their development. This study aimed to investigate the role of the gut microbiota in MASLD using an obese diabetic (ob/ob) mouse model and to evaluate the effects of Lactobacillus acidophilus.
Method: A total of 118 stool samples divided into three groups (Healthy control;n=39, MAFLD patients; n=36, MASH patients; n=43) In C57BL/6 obob mice, L.acidophilus oral gavage a concentration of 10^9 CFU/g two times a week, for 12 weeks staring at 6 weeks after birth. Metformin oral gavage a 200mg/kg daily as a positive control. We compared liver/body weight ratio (L/B ratio), NAFLD activity score (NAS), Oral glucose tolerance test (OGTT) Mice liver was collected for Histological (H&E), mRNA analysis and protein estimation, and the signaling pathways for inflammation and glucose metabolism-related gene expression in the liver were evaluated.
Result: The abundance of the Lactobacillus genus decreased with progression of liver disease. Oral administration of L.acidophilus reduced the area under the curve in the oral glucose tolerance test (OGTT) and alleviated hepatic inflammation, as shown by decreased mRNA expression of Tnf-α and Il6. L. acidophilus supplementation decreased the expression of Srebp-1c, thereby limiting hepatic lipogenesis. The mRNA levels of gluconeogenic genes, including Pepck and G6pc, were also reduced. In parallel, phosphorylation of Akt and AMPK was increased, supporting improved regulation of glucose metabolism in the liver. Collectively, these effects suggest that L. acidophilus ameliorates MASLD and gut microbial dysbiosis by modulating the gut microbiota and its metabolites, resulting in reduced hepatic inflammation, steatosis, and fatty acid synthesis.
Conclusion: Our findings suggest that Lactobacillus acidophilus may help alleviate features of MASLD by improving glucose metabolism and reducing lipid accumulation and inflammation in the liver. These results support the potential of L. acidophilus in preventing the progression of MASLD and offer new insights into microbiome-based strategies for metabolic disorders.
