Therapeutic modulation of the gut-liver axis with faecalibacterium prausnitzii in metabolic dysfunction-associated steatohepatitis.

BACKGROUND

Faecalibacterium prausnitzii (F. prausnitzii) has attracted interest in recent research regarding its possible involvement in metabolic dysfunction-associated steatotic liver disease (MASLD). However, their causal relationship is still unclear.

METHODS

Microbial biomarkers of gut microbiota associated with obesity-related phenotypes were identified from the GMrepo database. Information was retrieved on specific metabolites and host genes related to F. prausnitzii from the GutMGene database. Subsequently, a high-fat diet (HFD) was administered to C57BL/6 J mice for 16 weeks. The intragastric injection of F. prausnitzii ATCC 27766 strain was administered and changes in serum and liver metabolic indicators were then assessed. Fecal short-chain fatty acids (SCFAs) were measured using Gas chromatography-mass spectrometry (GC–MS). RNA-sequence (RNA-seq) was performed to identify differentially expressed genes related to F. prausnitzii treatment.

RESULTS

In individuals with obesity, MASLD, and Type 2 diabetes, the abundance of F. prausnitzii was significantly reduced by 22.4%, 16.2%, and 34%, respectively, compared to healthy controls (all p-values < 0.05). In comparison to HFD-fed control mice, those administered F. prausnitzii exhibited a substantial reduction in liver index (17.5%, p < 0.05), along with a 17.6% decrease in serum total cholesterol (TC) and a 12.7% decrease in triglycerides (TG) (all p-values < 0.05). Additionally, there was a substantial increase in the serum interleukin-10 (IL-10, 20.6%) levels and reduction in expressions of pro-inflammatory cytokines, including interleukin-1α (21.1%), IL-2 (32.2%), IL-5 (18.4%), and IL-6 (29.6%). GC–MS analysis confirmed a 91.4% increase in total fecal SCFAs concentrations, including acetic (91.9%), propionic (93.8%), and butyric acids (93.0%), with all p-values < 0.01. Both RNA-seq and polymerase chain reaction analyses consistently identified substantial changes in genes associated with de novo lipogenesis (Srebp-1c, Fas, Acc), fatty acid oxidation (PPARα, Acadvl, Acadm and Cpt2), and oxidative phosphorylation (Cox5b, Sdhb), with all p-values < 0.01.

CONCLUSION

This study highlights the promise of F. prausnitzii ATCC 27766 strain, especially regarding its anti-inflammatory and metabolic regulatory functions, as a next-generation probiotic agent in prevention and treatment of MASLD.