The effect of heat‐killed <i>Lactobacillus brevis</i> SBL88 on improving selective hepatic insulin resistance in non‐alcoholic fatty liver disease mice without altering the gut microbiota

doi:10.1111/jgh.16337

DOI: 10.1111/jgh.16337 ISSN:

The effect of heat‐killed Lactobacillus brevis SBL88 on improving selective hepatic insulin resistance in non‐alcoholic fatty liver disease mice without altering the gut microbiota

Hidemi Hayashi, Koji Sawada, Hiroki Tanaka, Kazuki Muro, Takumu Hasebe, Shunsuke Nakajima, Toshikatsu Okumura, Mikihiro Fujiya

Gastroenterology
Hepatology

Show PDF Cite

Abstract

Background and Aim

There have been several reports that some probiotics improve non‐alcoholic fatty liver disease (NAFLD); however, many studies have involved cocktail therapies. We evaluated whether heat‐killed Lactobacillus brevis SBL88 (L. brevis SBL88) monotherapy improves the clinical features of NAFLD.

Methods

The NAFLD model was induced in mice fed a high‐fat diet (HFD) (HFD mice) or HFD + 1% heat‐killed L. brevis SBL88 (SBL mice) for 16 weeks. Histopathological liver findings were analyzed. To evaluate the gut microbiota, a modified terminal restriction fragment length polymorphism analysis of the feces was performed. RNA sequencing in the liver was performed with Ion Proton™. To investigate the direct effects of heat‐killed L. brevis SBL88, an in vitro study was performed.

Results

Histopathological findings revealed that fat droplets in the liver were significantly reduced in SBL mice; however, terminal restriction fragment length polymorphism did not show alterations in the gut microbiota between HFD mice and SBL mice. RNA sequencing and pathway analysis revealed that the regulation of lipid and insulin metabolism was affected. The mRNA expression of insulin receptor substrate 2 (IRS‐2) was significantly higher in SBL mice, whereas the expression of IRS‐1 was not significantly different. Phospho‐IRS‐2 expression was also significantly increased in SBL mice. In addition, an in vitro study revealed significant alterations in IRS‐2 and forkhead box protein O1 expression levels.

Conclusion

SBL mice exhibited partially improved selective hepatic insulin resistance. Our data suggest that heat‐killed L. brevis SBL88 could attenuate the clinical features of NAFLD that are not mediated by alterations in the gut microbiota.