Lactobacillus plantarum alleviates high-fat diet-induced obesity by altering the structure of mice intestinal microbial communities and serum metabolic profiles

Abstract

Obesity, which is always accompanied by disorders of lipid metabolism and dysbiosis of the gut microbiota, has become a global epidemic recognised by the World Health Organisation, necessitating innovative strategies and a globally accepted agreement on treating obesity and its related complications. Probiotics, as major active ingredients in many foods, offer potential as biological treatments for obesity prevention and management. Lactobacillus plantarum (L. plantarum) possesses a wide range of biological activities and is widely used to alleviate and ameliorate various diseases. This research demonstrated that Lactobacillus plantarum reduces the weight increase and fat build-up caused by a high-fat diet (HFD) in mice, while also improving glucose tolerance and insulin sensitivity in obese mice. Results indicated that L. plantarum effectively controlled the intestinal microbial community's structure, counteracted disruptions in gut flora caused by HFD, normalized the Firmicutes to Bacteroidota ratio (F/B), and decreased the prevalence of detrimental bacteria Desulfovibrio and Clostridia. Serum metabolomics findings indicate notable alterations in serum metabolites across various groups, notably the increased levels of Isoprothiolane and Inosine, key regulators of lipid metabolism disorders and enhancers of fat burning. These differential metabolites were mainly enriched in unsaturated fatty acid biosynthesis, sulfur metabolism, fatty acid biosynthesis, and purine metabolism. Consequently, we propose that L. plantarum has the potential to alter the gut microbial community's composition, positioning it as a promising option for obesity therapy.

Keywords: Lactobacillus plantarum; differential metabolites; fat metabolism; intestinal microbes; obesity; probiotics.

Figure 1

Experimental group assignment and workflow. The 30 mice were divided into three different groups (CON group, HFD group and HFD-ZW group) for 15 weeks.

Figure 2

L. plantarum on body weight in obese mice. (A) Change in body weight of mice. (B–E) Weight changes in each treatment group during gavage. Data are means ± standard deviation and were analysed by one-way ANOVA. *p < 0.05 (n = 5).

Figure 3

Effect of L. plantarum on glucose tolerance and insulin resistance in obese mice. (A) Plasma glucose levels in the mice glucose tolerance test; (B) plasma glucose levels in the mice insulin resistance test.

Figure 4

Effects of L. plantarum on adipocyte and liver histological changes in obese mice. (A) Changes in subcutaneous fat weight; (B) changes in visceral fat weight; (C) histological changes in liver sections measured by H&E staining with 20×, 40× and 63× magnification, respectively. Data are mean ± standard deviation and were analysed by one-way ANOVA. *p < 0.05 (n = 5).

Figure 5

Effect of L. plantarum treatment on microbial species richness, α and β diversity indices in mice colon. (A) Venn diagram of OTU distribution. (B) ACE index. (C) Chao 1 index. (D) Shannon’s index. (E) Simpson’s index. (F) Principal co-ordinate analysis (PCoA) showing microbial community distances between baseline of the CON group (blue circles), the HFD group (red circles), and the baseline of the group after L. plantarum intervention (green circles). (G) Unweighted pair group method with arithmetic mean (UPGMA) analysis. Data are means ± standard deviation and were analyzed using one-way ANOVA. *p < 0.05 (n = 5).

Figure 6

Analysis of microbial components at the phylum level. (A) Relative abundance of microbial phyla in the mice colon. Components of the relative abundance of the Bacteoidota (B), Firmicutes (C), F/B ratio (D), Proteobacteria (E), Actinobacteria (F), and Desulfobacterota (G) in the colons of mice in the CON, HFD, and HFD-ZW groups. *p < 0.05 (n = 5).

Figure 7

Analysis of microbial components at the class level. (A) Relative abundance of microbial class in the mice colon. Components of the relative abundance of Bacteroidia (B), Clostridia (C), Bacilli (D), Actinobacteria (E), and Deferribacteres (F) in the colons of mice in the CON, HFD, and HFD-ZW groups. *p < 0.05 (n = 5).

Figure 8

Analysis of microbial components at the genus level. (A) Relative abundance of microbial genus in the mice colon. Components of the relative abundance of Dubosiella (B), Parasutterella (C), Desulfovibrio (D), Bacteroides (E), and Odoribacter (F) in the colons of mice in the CON, HFD, and HFD-ZW groups. *p < 0.05 (n = 5).

Figure 9

Characterisation of mice colonic microorganisms identified by L. plantarum treatment. (A) LEfSe taxonomic branching diagram, different colours indicate enrichment of certain taxonomic units in the CON group (green), the HFD group (orange) and the HFD-ZW group (purple); (B) LDA scores, LDA scores higher than 2 were considered to be significant contributors to the model.

Figure 10

Differential metabolite and KEGG pathway enrichment analysis results. (A) Analysis of differential metabolites between CON and HFD; (B) results of enrichment analysis of KEGG pathways between CON and HFD; (C) analysis of differential metabolites between HFD and HFD-ZW; (D) results of enrichment analysis of KEGG pathways between HFD and HFD-ZW.

Figure 11

Spearman correlation analysis of gut flora with serum metabolites. (A) Network plot of gut flora correlation in mice; (B) heat map of gut differential microbiota versus raw serum differential metabolites. *p < 0.05 and **p < 0.01.