Lactobacillus brevis Alleviates DSS-Induced Colitis by Reprograming Intestinal Microbiota and Influencing Serum Metabolome in Murine Model

Abstract

The aim of this study was to examine the effects of Lactobacillus brevis on the microbial community and serum metabolome in colitis induced by dextran sulfate sodium (DSS). ICR mice were randomly distributed into three treatment groups: (i) L. brevis treatment alone (control), (ii) DSS administration alone, and (iii) treatment with L. brevis and DSS. Our results demonstrate that L. brevis treatment significantly alleviated DSS-induced body weight loss and colon inflammation. In addition, LC-MS analysis of serum metabolites revealed that L. brevis treatment increased the serum level of metabolites against inflammatory responses or oxidative stressors caused by DSS in the murine model. By detecting colonic microbiota, L. brevis increased colonic microbial diversity after challenging with DSS, and increased the relative abundance of Alloprevotella at genus, but Bacteroidales was reduced (P < 0.05). These result indicated that L. brevis could lower the severity of colitis induced by DSS via improving reprogramming the serum metabolome and intestinal microbiota. These findings suggest that the probiotic L. brevis may prevent tissue damage from colitis.

Keywords: Lactobacillus brevis; colitis; intestinal microbiota; metabolome; murine.

FIGURE 1

Effects of L. brevis on DSS-induced colitis. (A) Final weight of the control, DSS, and LB-DSS mice. (B) Length of the colon of control, DSS, and LB-DSS mice. (C) Weight of the colon of control, DSS, and LB-DSS mice. ^∗P < 0.05.

FIGURE 2

Severity of colon tissue inflammation in mice given with DSS. Effects of L. brevis on colonic histology (A: control; B: DSS; C: LB-DSS), and corresponding histologic severity scores (D). ^∗P < 0.05.

FIGURE 3

Score plots of principal component analysis (PCA) and OPLS-DA models with their corresponding R2X and T2 values. PCA score plots among the three groups in positive ion mode (A1) or negative ion mode (A2), PCA (B1,C1) and PLS-DA (B2,C2) score plots between two groups in positive mode, and PCA (B3,C3) and PLS-DA (B4,C4) score plots between two groups in negative mode.

FIGURE 4

Diversity indexes of microbiota in the mouse colon. Vox plots depict the Chao index (A), ACE index (B), Shannon index (C), and Simpson index (D) of the colonic microbiota of the control, DSS, and LB-DSS mice. ^∗P < 0.05.

FIGURE 5

Analysis of the microbial composition at the phylum level. (A) Relative abundances of microbial phyla in the mouse colon. Comparisons of the relative abundances of Bacteroidetes (B), Firmicutes (C), Proteobacteria (D), and Actinobacterial (E) in the colon of control, DSS, and LB-DSS mice. ^∗P < 0.05.

FIGURE 6

Analysis of the microbial composition at the order level. (A) Relative abundances of microbial orders in the mouse colon. Comparisons of the relative abundances of Verrucomicrobiales (B), Bacteroidales (C), Lactobacillales (D), Burkholderiales (E), Clostridiales (F), and Erysipelotrichales (G) in the colon of control, DSS, and LB-DSS mice. ^∗P < 0.05.

FIGURE 7

Analysis of the microbial composition at the genus level. (A) Relative abundances of microbial genera in the mouse colon. Comparisons of relative abundance of Akkermansia (B), Bacteroides (C), Lactobacillus (D), Parasutterella (E), Alloprevotella (F), and Desulfovibrio (G) in the colon of control, DSS, and LB-DSS mice. ^∗P < 0.05.

FIGURE 8

Correlation analysis of serum metabolites and colonic microbes. (A) Serotonin vs. Bacteroidetes, (B) serotonin vs. Bacteroidales, (C) serotonin vs. Lactobacillus, (D) arachidonic acid vs. Bacteroidetes, (E) arachidonic acid vs. Bacteroidales, and (F) N1-acetylspermidine vs. Lactobacillus.