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. 2020 Jul 3;11(4):882-899.
doi: 10.1080/19490976.2020.1712984. Epub 2020 Jan 22.

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

Na Young Lee  1 , Sang Jun Yoon  1 , Dae Hee Han  1 , Haripriya Gupta  1 , Gi Soo Youn  1 , Min Jea Shin  1 , Young Lim Ham  2 , Min Jung Kwak  3 , Byung Yong Kim  3 , Jeong Seok Yu  4   5 , Do Yup Lee  5 , Tae-Sik Park  6 , Si-Hyun Park  6 , Byoung Kook Kim  7 , Hyun Chae Joung  7 , In Suk Choi  7 , Ji Taek Hong  1   8 , Dong Joon Kim  1   8 , Sang Hak Han  9 , Ki Tae Suk  1   8
Affiliations

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

Na Young Lee et al. Gut Microbes. .

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; microbiome; strains.

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Figures

Figure 1.
Figure 1.
Flow chart of the animal experiment.
Figure 2.
Figure 2.
Effect of probiotics on liver. (a) Effect of dietary on liver/body weight ratio in mice. Compared with mice fed western diet. (b) Gross specimen of mice liver.
Figure 3.
Figure 3.
Pathological effects of probiotics on the liver (Hematoxylin and Eosin stain). (a) Steatosis grade. normal control (a), Western diet (b), L. bulgaricus (c), L. casei (d), L. helveticus (e), P. pentosaceus KID7 (f), combination 1 (g), combination 2 (h), and combination 3 (i). (B) Inflammation grade. Mild to moderate inflammation, favoring lymphocytes, is identified in the perivenular area (b, arrow).
Figure 4.
Figure 4.
Gut-liver axis analysis. (a) NAFLD Activity Score (NAS). (b) Immunohistochemical analyses for CD68 in representative cases. normal control (a), Western diet (b), L. bulgaricus (c), L. casei (d), L. helveticus (e), P. pentosaceus KID7 (f), combination 1 (g), combination 2 (h), and combination 3 (i). x400. (C) Stool endotoxin level. (D) Trans-epithelial electrical resistance (TEER) measurement.
Figure 5.
Figure 5.
Results of animal stool analysis. (a) Phylum analysis. (b) Analytics for beta diversity for the relationship between microbiome taxonomic profiling (principle coordinates analysis, Jensen-Shannon, species, include unclassified OTUs). (c) Comparison of the 10 prevalent species. (d) Firmicutes/Bacteroidetes ratio. (e) Heatmap for comparison of species diversity in mice feces.
Figure 6.
Figure 6.
Unique primary metabolic profiles of the cecal samples according to different strains. (a) The heatmap generated by hierarchical clustering analysis of 140 metabolites from the cecal samples. (b) Box-and-whisker plots of the metabolites that represent characteristic abundances in P. pentosaceus KID7 treatment group compatible with the normal control group.
Figure 7.
Figure 7.
Probiotics block proinflammatory cytokines. (a) Enzyme-linked immunosorbent assay. (b and c) Real-time reverse transcription-polymerase chain reaction.
Figure 8.
Figure 8.
Schematic overview of gut-liver-axis modulation by probiotics.
See this image and copyright information in PMC

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