L. acidophilus supplementation attenuated hepatic steatosis and inflammatory injury in multiple complementary mouse models and improved glucose tolerance, through coordinated hepatic metabolic regulation and gut microbial modulation, supporting its potential as a probiotic candidate for MASLD and diabetes-associated metabolic disease.
Key Findings
Results
L. acidophilus supplementation attenuated hepatic steatosis and inflammatory injury across multiple complementary diet-induced and genetic mouse models of MASLD.
Models tested included Western diet, fructose-palmitate-cholesterol diet, high-fat diet, and leptin-deficient ob/ob mice.
Multiple complementary models were used to systematically investigate the effects of L. acidophilus across the MASLD disease continuum.
Hepatic steatosis attenuation was observed consistently across the different dietary and genetic model systems.
The use of four distinct models strengthened the generalizability of the hepatic findings.
Results
L. acidophilus supplementation improved glucose tolerance in leptin-deficient ob/ob mice.
The ob/ob mouse model is a genetic model of severe obesity and diabetes characterized by leptin deficiency.
Improvement in glucose tolerance was observed in this diabetic model following L. acidophilus treatment.
This finding extended the metabolic benefits of L. acidophilus beyond hepatic steatosis to glycemic regulation.
The ob/ob model represents a relevant context for studying diabetes-associated metabolic disease.
Results
L. acidophilus supplementation reduced hepatic expression of pro-inflammatory cytokines in mouse models.
Reduced hepatic expression of pro-inflammatory cytokines was documented alongside attenuation of hepatic steatosis.
These anti-inflammatory effects were observed across multiple model systems.
The reduction in pro-inflammatory cytokine expression accompanied the observed improvements in hepatic injury.
This suggests L. acidophilus exerts hepatoprotective effects partly through modulation of hepatic inflammation.
Results
L. acidophilus supplementation altered AMPK-associated signaling and the expression of lipogenic and gluconeogenic genes in the liver.
Changes in AMPK-associated signaling were observed following L. acidophilus supplementation.
Expression of lipogenic genes Srebf1 (SREBP-1c) and Acc (acetyl-CoA carboxylase) was decreased.
Expression of gluconeogenic genes Pepck (phosphoenolpyruvate carboxykinase) and G6pc (glucose-6-phosphatase) was decreased.
Increased Ppara (PPARĪ±) expression was also observed, suggesting coordinated regulation of glucose and lipid metabolism.
Results
Transcriptomic profiling revealed that L. acidophilus influenced broader metabolic networks including altered expression of Lpin1 and enrichment of pathways related to nutrient sensing and metabolic regulation.
Transcriptomic profiling was used to characterize the broader hepatic effects of L. acidophilus supplementation.
Altered expression of Lpin1 (lipin-1), a key regulator of lipid metabolism, was identified.
Pathways related to nutrient sensing and metabolic regulation were enriched in the transcriptomic analysis.
These findings indicate that L. acidophilus effects extend beyond individual gene targets to broader metabolic networks.
Results
L. acidophilus supplementation altered gut microbial community structure in mouse models.
Changes in gut microbial community structure were observed in the mouse models receiving L. acidophilus.
These microbial alterations accompanied the hepatic and metabolic improvements.
The findings suggest that gut microbial modulation is part of the mechanism by which L. acidophilus exerts its effects.
The relationship between microbial changes and metabolic outcomes supports a gut-liver axis mechanism.
Results
Human cohort analyses revealed context-dependent microbial patterns involving Lactobacillus, Akkermansia, and butyrate-producing Firmicutes across metabolic disease states.
A clinical cohort was used to validate disease-associated microbial patterns and inform candidate strain selection.
Context-dependent patterns were observed, meaning microbial associations differed depending on the specific metabolic disease state (MASLD vs. diabetes).
Key taxa identified in the human cohort included Lactobacillus, Akkermansia, and butyrate-producing Firmicutes.
Validation in the clinical cohort preceded and informed the selection of L. acidophilus as the candidate probiotic strain.
The human cohort data provided clinical relevance for the mechanistic findings from mouse models.
Methods
L. acidophilus was selected as a candidate probiotic strain based on validation of disease-associated microbial patterns in a clinical cohort.
The study design began with clinical cohort validation before proceeding to experimental animal models.
Disease-associated microbial patterns in MASLD and diabetes were characterized in human subjects first.
This translational approach grounded the experimental work in clinically observed dysbiosis patterns.
The selection of L. acidophilus was thus data-driven from human microbial data.
What This Means
This research investigated whether a specific probiotic bacterium, Lactobacillus acidophilus, could help address two common and related metabolic diseases: metabolic dysfunction-associated steatotic liver disease (MASLD, formerly known as non-alcoholic fatty liver disease) and diabetes. The researchers first analyzed gut bacteria patterns in human patients with these conditions, then used those findings to select L. acidophilus as a promising candidate for testing. They then tested the probiotic across four different mouse models of metabolic disease, including mice fed unhealthy diets and a genetic mouse model of obesity and diabetes. Across all models, L. acidophilus reduced fat buildup and inflammation in the liver, and in the diabetic mouse model, it also improved the ability to regulate blood sugar.
The research suggests that L. acidophilus works through several coordinated mechanisms. It reduced the activity of genes responsible for making fat (lipogenesis) and producing glucose in the liver (gluconeogenesis), while increasing the activity of a gene (PPARĪ±) that helps burn fat. It also affected a key cellular energy-sensing pathway (AMPK signaling). A broad analysis of gene activity in the liver confirmed that L. acidophilus influenced wide-ranging metabolic networks. Additionally, the probiotic changed the composition of gut bacteria in the mice, and the human data showed that specific bacteria including Lactobacillus, Akkermansia, and butyrate-producing bacteria were associated with different metabolic disease states in distinct patterns.
This research suggests that L. acidophilus could be a promising probiotic for people with fatty liver disease and diabetes by simultaneously improving liver health, blood sugar regulation, and gut bacterial balance. The fact that benefits were seen across multiple different experimental models strengthens confidence in these findings. However, this work was primarily conducted in mice, and further human clinical trials would be needed to confirm whether these benefits translate directly to people.
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Park H, Park I, Park J, Park H, Jung J, Han S, et al.. (2026). Effects of Lactobacillus acidophilus on hepatic and microbial dysregulation in MASLD and diabetes.. Gut microbes. https://doi.org/10.1080/19490976.2026.2734705