Lactobacillus and Pediococcus ameliorate progression of non-alcoholic fatty liver disease through modulation of the gut microbiome

ABSTRACT

Targeting the gut-liver axis by modulating the gut-microbiome can be a promising therapeutic approach in nonalcoholic fatty liver disease (NAFLD). The aim of this study was to evaluate the effects of single species and a combination of Lactobacillus and Pediococcus in NAFLD mice model. Six-week male C57BL/6J mice were divided into 9 groups (n = 10/group; normal, Western diet, and 7 Western diet-strains [10⁹ CFU/g, 8 weeks]). The strains used were L. bulgaricus, L. casei, L. helveticus, P. pentosaceus KID7, and three combinations (1: L. casei+L. helveticus, 2: L. casei+L. helveticus+P. pentosaceus KID7, and 3: L. casei+L. helveticus+L. bulgaricus). Liver/Body weight ratio, serum and stool analysis, liver pathology, and metagenomics by 16S rRNA-sequencing were examined. In the liver/body ratio, L. bulgaricus (5.1 ± 0.5), L. helveticus (5.2 ± 0.4), P. pentosaceus KID7 (5.5 ± 0.5), and combination1 and 2 (4.2 ± 0.6 and 4.8 ± 0.7) showed significant reductions compared with Western (6.2 ± 0.6)(p < 0.001). In terms of cholesterol and steatosis/inflammation/NAFLD activity, all groups except for L. casei were associated with an improvement (p < .05). The elevated level of tumor necrosis factor-α/interleukin-1β (pg/ml) in Western (65.8 ± 7.9/163.8 ± 12.2) was found to be significantly reduced in L. bulgaricus (24.2 ± 1.0/58.9 ± 15.3), L. casei (35.6 ± 2.1/62.9 ± 6.0), L. helveticus (43.4 ± 3.2/53.6 ± 7.5), and P. pentosaceus KID7 (22.9 ± 3.4/59.7 ± 12.2)(p < 0.01). Cytokines were improved in the combination groups. In metagenomics, each strains revealed a different composition and elevated Firmicutes/Bacteroidetes ratio in the western (47.1) was decreased in L. bulgaricus (14.5), L. helveticus (3.0), and P. pentosaceus KID7 (13.3). L. bulgaricus, L. casei, L. helveticus, and P. pentosaceus KID7 supplementation can improve NAFLD-progression by modulating gut-microbiome and inflammatory pathway.

KEYWORDS:

• Nonalcoholic fatty liver disease
• gut liver axis
• liver function
• strains
• microbiome

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Author contributions

NYL, SJY, DHH, SHH, and KTS designed the study and interpreted the work. NYL, SHH, and KTS wrote the manuscript. HG, GSY, MJS, YLH, MJK, BYK, JSY, DYL, TSP, SHP, BKK, HCJ, and ISC performed experiments. JTH and DJK provided tissue specimens. All authors contributed to manuscript revision, and read and approved the submitted version.

Disclosure of potential conflicts of interest

Authors MJK and BYK were employed by company ChunLab, Inc. Authors BKJ, HCJ, and ISC were employed by company Chong Kun Dang Bio. All other authors attest that there are no commercial associations that might be a conflict of interest in relation to the submitted manuscript.

Ethical approval statement

The animals received humane care and all procedures were performed in accordance with National Institutes of Health Guidelines for the Care and Use of Laboratory Animals. All procedures were approved by the Institutional Animal Care and Use Committee of the College of Medicine, Hallym University (2018-04).

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This research was supported by Hallym University Research Fund, Korea National Research Foundation (NRF-2018M3A9F3020956 and NRF-2018M3A9F3020942), and Hallym University Research Fund 2018 (HURF-2018-67).