<i>Lactobacillus</i>and<i>Pediococcus</i>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 <i>Lactobacillus</i> and <i>Pediococcus</i> 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 <i>L. bulgaricus, L. casei, L. helveticus, P. pentosaceus</i> KID7, and three combinations (1: <i>L. casei+L. helveticus</i>, 2: <i>L. casei+L. helveticus+P. pentosaceus</i> KID7, and 3: <i>L. casei+L. helveticus+L. bulgaricus</i>). Liver/Body weight ratio, serum and stool analysis, liver pathology, and metagenomics by 16S rRNA-sequencing were examined. In the liver/body ratio, <i>L. bulgaricus</i> (5.1 ± 0.5), <i>L. helveticus</i> (5.2 ± 0.4), <i>P. pentosaceus</i> 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 <i>L. casei</i> were associated with an improvement (<i>p</i> < .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 <i>L. bulgaricus</i> (24.2 ± 1.0/58.9 ± 15.3), <i>L. casei</i> (35.6 ± 2.1/62.9 ± 6.0), <i>L. helveticus</i> (43.4 ± 3.2/53.6 ± 7.5), and <i>P. pentosaceus</i> 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 <i>Firmicutes</i>/<i>Bacteroidetes</i> ratio in the western (47.1) was decreased in <i>L. bulgaricus</i> (14.5), <i>L. helveticus</i> (3.0), and <i>P. pentosaceus</i> KID7 (13.3). <i>L. bulgaricus, L. casei, L. helveticus</i>, and <i>P. pentosaceus</i> KID7 supplementation can improve NAFLD-progression by modulating gut-microbiome and inflammatory pathway.