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. 2023 May 19:10:1160069.
doi: 10.3389/fnut.2023.1160069. eCollection 2023.

Deciphering the mechanism of jujube vinegar on hyperlipoidemia through gut microbiome based on 16S rRNA, BugBase analysis, and the stamp analysis of KEEG

Guofeng Duan  1 , Lijuan Li  2
Affiliations

Deciphering the mechanism of jujube vinegar on hyperlipoidemia through gut microbiome based on 16S rRNA, BugBase analysis, and the stamp analysis of KEEG

Guofeng Duan et al. Front Nutr. .

Abstract

Background: Growing data indicate that the gut microbiome may contribute to the rising incidence of hyperlipoidemia. Jujube vinegar lowers lipids, protects the liver, and reduces oxidant capacity, however, it is unknown whether this is due to the gut flora. To further research the role of the gut microbiome in treating hyperlipidemia with jujube vinegar, we looked into whether the action of jujube vinegar is related to the regulation of the gut microbiome.

Method: Thirty male ICR mice were used. The control group (CON), the high-fat diet (HFD) group, and the vinegar group (VIN) each consisted of ten female ICR mice fed consistently for eight weeks. For each treatment, we kept track of body mass, liver index, blood lipid levels, and oxidative stress state. We also analyzed mouse feces using high-throughput 16srRNA sequencing to examine the relationship between jujube vinegar's hypolipidemic effect and antioxidant activity and how it affects the gut microbiome.

Results: Jujube vinegar reduced body weight by 19.92%, serum TC, TG, and LDL-C by 25.09%, 26.83%, and 11.66%, and increased HDL-C by 1.44 times, serum AST and ALT decreased by 26.36% and 34.87% respectively, the blood levels of SOD and GSH-Px increased 1.35-fold and 1.60-fold, respectively. While blood MDA decreased 33.21%, the liver's SOD and GSH-Px increased 1.32-fold and 1.60-fold, respectively, and the liver's MDA decreased 48.96% in HFD mice. The gut microbiome analysis revealed that jujube vinegar increased the intestinal microbial ASV count by 13.46%, and the F/B (Firmicutes/Bacteroidota) ratio by 2.08-fold in high-fat diet mice, and the proportion was significantly inversely correlated with TC, TG, and LDL-C and positively correlated with HDL-C. Biomarker bacteria in the vinegar group included Lactobacillaceae and Lactobacillus, which correlated favorably with HDL-C, SOD, and GSH-Px and negatively with LDL-C, TC, and TG. Jujube vinegar increased the abundance of the Aerobic, Contains Mobile Elements, and Facultative Aerobic by 2.84 times, 1.45 times, and 2.40 times, while decreased the abundance of Potential pathogens by 44.72%, according to the BugBase study. The KEGG analysis showed that jujube vinegar was predominantly reflected in the biological process of gene function and related to signal transduction pathways, including glucagon signaling system, HIF-1 signaling pathway, adipocytokine signaling pathway, amino sugar, and nucleotide sugar metabolism, and so forth.

Conclusion: Based on these findings, jujube vinegar may reduce hyperlipoidemia by controlling the gut microbiome and enhancing antioxidant capacity.

Keywords: BugBase; gut microbiome; high-fat diet; hyperlipoidemia; jujube vinegar.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Effects of Jujube vinegar on body weight, liver index, and abdominal fat index in HFD-fed mice. (A) Body weight, (B) liver index. (C) abdominal fat index. Data are expressed as the means ± SEM, n = 10. Lowercase letters indicate significant differences (p < 0.05), uppercase letters indicate highly significant differences (p < 0.01), the same below.
Figure 2
Figure 2
Effects of Jujube vinegar on serum lipid metabolism in HFD-fed mice. (A) Serum HDL-C concentration, (B) serum LDL-C concentration, (C) serum TC concentration, (D) serum TG concentration, (E) serum AST concentration, (F) ALT concentration. Data are expressed as the means ± SEM, n = 10.
Figure 3
Figure 3
Jujube vinegar enhanced the antioxidant capacity in HFD-fed mice. (A) Serum MDA concentration, (B) serum SOD activity, (C) serum GSH-Px activity, (D) liver MDA concentration, (E) liver SOD activity, (F) liver GSH-Px activity. Data are expressed as the means ± SEM, n = 10.
Figure 4
Figure 4
Diversities analysis of gut microbiome in mice among groups. (A) Venn graph, (B) OTU numbers, (C) ACE index of ɑ diversities analysis, (D) Chao 1 index of ɑ diversities analysis, (E) Shannon index of ɑ diversities analysis, (F) Simpson index of ɑ diversities analysis, (G) PCA analysis, (H) PCoA analyses, (I) Anosim analysis. Data are expressed as the means ± SEM, n = 6.
Figure 5
Figure 5
Phylum classification differences in gut microbiome among three groups. (A) Relative abundance distribution at phylum levels, (B) Firmicutes relative abundance, (C) Bacteroidota relative abundance, (D) Firmicutes/Bacteroidota (F/B) ratio, (E) the correlation of F/B and HDL-C, (F) the correlation of F/B and LDL-C, (G) the correlation of F/B and TC, (H) the correlation of F/B and TG. Data are expressed as the means ± SEM, n = 6.
Figure 6
Figure 6
Relative abundances of gut microbiome in mice at the genus level. (A) A bar graph of genus distribution with a TOP 10 abundance, (B) relative abundance of Bacteroidota genus, (C) relative abundance of unclassified_Oscillospiraceae genus, (D) relative abundance of Alistipes genus, (E) relative abundance of unclassified_Desulfovibrionaceae genus, (F) relative abundance of Bilophila genus. Data are expressed as the means ± SEM, n = 6.
Figure 7
Figure 7
Lefse branch plot. (A) Histogram of distribution of LDA values reveal the microbiome of different taxa among the three groups. Panel (B) shows the different bacterial-rich taxa among the three groups. The concentric rings are species, genus, family, order, class, phylum, and so on. Blue, orange, and green show different bacterial taxa in the control, HFD and Vinegar groups, respectively, and yellow shows no significant differences between groups.
Figure 8
Figure 8
Analysis of the correlation between gut microbiota and blood lipid indexes antioxidant performance. (A) The correlation between gut microbiota and blood lipid index at phylum level, (B) the correlation between gut microbiota and blood lipid index at genus level, (C) the correlation between gut microbiota and antioxidant biomarker at phylum level, (D) the correlation between gut microbiota and antioxidant biomarker at genus level. *p < 0.05, **p < 0.05, ***p < 0.001.
Figure 9
Figure 9
Prediction of BugBase phenotype. (A) Aerobic abundance, (B) Anaerobic abundance, (C) Facultatively_Anaerobic abundance, (D) Contains_Mobile_Elements abundance, (E) Potentially_pathogenic abundance, (F) Stress-tolerant abundance, (G) Gram_positive abundance, (H) Gram_negative abundance, (I) Forms_Biofilms abundance.
Figure 10
Figure 10
BugBase analysis of relative abundance of bacterial genera in mice. (A) Aerobic, (B) Anaerobic, (C) Contains_Mobile_Elements, (D) Facultatively_Anaerobic, (E) Forms_Biofilms, (F) Gram_Negative, (G) Gram_Positive, (H) Potential_Pathogens, (I) Stress_Tolerant.
Figure 11
Figure 11
Histogram of KEGG pathway abundance and stamp analysis at level 3. (A) Stamp analysis between the control group and the HFD group, (B) Stamp analysis between the control group and the vinegar group, (C) Stamp analysis between the HFD group and the vinegar group.
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