Emerging evidence suggests that probiotics are beneficial in non-alcoholic fatty liver disease (NAFLD). This study aimed to explore the effects of two Lactobacillus plantarum strains, ATG-K2 and ATG-K6 (isolated from Korean fermented cabbage), in a rat model of high fat/high fructose (HF/HF) diet-induced NAFLD. Rats with NAFLD were randomized into four groups (HF/HF diet control, (HC); HF/HF diet with silymarin, (PC); HF/HF diet with ATG-K2, (K2); and HF/HF diet with ATG-K6, (K6)) with healthy rats on a normal diet serving as the negative control. After treatment, histopathological and biochemical analyses of the blood and liver tissue were conducted. In addition, fecal microbiota was analyzed using the MiSeq platform. Compared with HC rats, K2 and K6 rats experienced significantly lower body weight gain, displayed decreased hepatic lipid accumulation, had lower serum levels of aspartate aminotransferase and alanine aminotransferase, and showed increased antioxidant enzyme activities. Moreover, de novo lipogenesis-related genes were downregulated following K2 and K6 administration. The fecal microbiota of K2 and K6 rats contained a higher proportion of Bacteriodetes and a lower proportion of Fimicutes than that of HC rats. Taken together, our results suggest that L. plantarum strains ATG-K2 and ATG-K6 are potential therapeutic agents for NAFLD.Nutrients 2020, 12, 542 2 of 16 of the transcription factors, such as sterol regulatory element binding protein 1c (SREBP-1c) and CCAAT/enhancer-binding protein alpha (C/EBPα), which in turn regulate the expression of hepatic gluconeogenesis and DNL genes [6]. It follows that fructose intake increases liver gluconeogenesis and DNL and elevates blood glucose and TG levels in humans [8,9] Another cause of NAFLD is oxidative stress. Fat deposition occurring in the liver results in lipid peroxidation, and it promotes a variety of responses such as inflammation and fibrosis. Thus, antioxidants (e.g., silymarin, vitamin E) are proposed as candidates for NAFLD treatment [10,11]; however, there are no standard pharmacological therapeutic agents for NAFLD yet. Recently, emerging evidence suggests that the gut-liver axis is strongly related to NAFLD. There are several reports published clinical trials applying probiotics on NAFLD patients [12]. Lactobacillus bulgaricus and Streptococcus thermophiles treatment improved liver aminotransferases levels in adult NAFLD patients [13]. In addition, probiotic capsules containing Lactobacillus acidophilus, Bifidobacterium lactis, Bifidobacterium bifidum, and Lactobacillus rhamnosus, as a supplement also decreased liver aminotransferases levels in obese children with NAFLD [14]. These results indicate that the intake of certain probiotics has a beneficial effect on NAFLD.Lactobacillus plantarum, which plays a key role in the production of various fermented foods, is one of the most important species of lactic acid bacteria (LAB). L. plantarum is found in diverse environments, such as the soil and the human gut, and is considered a potential pro...
Three Lactobacillus plantarum strains ATG-K2, ATG-K6, and ATG-K8 were isolated from Kimchi, a Korean traditional fermented food, and their probiotic potentials were examined. All three strains were free of antibiotic resistance, hemolysis, and biogenic amine production and therefore assumed to be safe, as supported by whole genome analyses. These strains demonstrated several basic probiotic functions including a wide range of antibacterial activity, bile salt hydrolase activity, hydrogen peroxide production, and heat resistance at 70°C for 60 s. Further studies of antimicrobial activities against Candida albicans and Gardnerella vaginalis revealed growth inhibitory effects from culture supernatants, coaggregation effects, and killing effects of the three probiotic strains, with better efficacy toward C. albicans. In vitro treatment of bacterial lysates of the probiotic strains to the RAW264.7 murine macrophage cell line resulted in innate immunity enhancement via IL-6 and TNF-α production without lipopolysaccharide (LPS) treatment and anti-inflammatory effects via significantly increased production of IL-10 when co-treated with LPS. However, the degree of probiotic effect was different for each strain as the highest TNF-α and the lowest IL-10 production by the RAW264.7 cell were observed in the K8 lysate treated group compared to the K2 and K6 lysate treated groups, which may be related to genomic differences such as chromosome size (K2: 3,034,884 bp, K6: 3,205,672 bp, K8: 3,221,272 bp), plasmid numbers (K2: 3, K6 and K8: 1), or total gene numbers (K2: 3,114, K6: 3,178, K8: 3,186). Although more correlative inspections to connect genomic information and biological functions are needed, genomic analyses of the three strains revealed distinct genomic compositions of each strain. Also, this finding suggests genome level analysis may be required to accurately identify microorganisms. Nevertheless, L. plantarum ATG-K2, ATG-K6, and ATG-K8 demonstrated their potential as probiotics for mucosal health improvement in both microbial and immunological contexts.
Psychobiotics are probiotic microorganisms that may exert positive influence on the psychological status of the host. Studies have revealed immunological and microbiological correlations of gut microbiota and the gut-brain axis, and have investigated psychobiotics based on the findings of the gut-brain axis. Considering their mode of actions, the present study sets anti-inflammatory effect, neurotransmitter modulation, and gut microbiota modulation as three essential criteria to evaluate Lactobacillus casei ATG-F1 (F1), L. reuteri ATG-F3 (F3), and L. reuteri ATG-F4 (F4) isolated from newborns as psychobiotics candidates in a healthy mouse model and compares the results with a non-treated control group and an ampicillin-induced gut dysbiosis (Amp) group as a negative control. The F3 and F4 strains showed anti-inflammatory effects in vitro in RAW264.7 murine macrophages, and the level of anti-inflammatory cytokine interleukin (IL)-10 increased in ileums of mice orally administered with the F4 strain. Serum dopamine level significantly increased only in the F4-treated group as compared with the control group. Serum serotonin level was unaffected in Lactobacillus -treated groups, while a significant decrease in serum serotonin level was observed in the Amp group. Bacteroidetes population increased in fecal samples of the F4-treated group as compared with the control, and Bacteroidales S24-7 and Prevotellaceae population significantly increased at family level in fecal samples from the F4-treated group as compared with the control. In contrast, the Amp group showed an increase in the level of Proteobacteria and a decrease in the level of Bacteroidetes as compared with the control group. Transcriptome analysis revealed a distinctive clustering in ileums from the F4-treated group as compared to other experimental groups. In addition, the circadian rhythm pathway showed maximum enrichment in ileums of Lactobacillus -treated mice, and the F4-treated group showed the highest fold changes in circadian rhythm-related genes ( Dbp, Per1, Per2 , and Per3 ). Conclusively, L. reuteri ATG-F4 is suggested as a potential psychobiotics through demonstrations of anti-inflammatory effects, serum dopamine modulation, and gut microbiota modulation in a healthy murine model in the present study. Moreover, we carefully suggest gut circadian rhythm modulation as another important criterion of psychobiotics, which may have an important role in the gut-brain axis.
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