Effects of Bacteroides-Based Microecologics against Antibiotic-Associated Diarrhea in Mice

Abstract

Antibiotic-associated diarrhea (AAD) is a self-limiting disease mediated by antibiotic therapy. In clinical practice, several types of probiotics are used in treating AAD, but minimal research has been done on Bacteroides-based microecologics. Our aim was to evaluate the therapeutic effects of Bacteroidetes uniformis FGDLZ48B1, B. intestinalis FJSWX61K18, Bifidobacterium adolescentis FHNFQ48M5, and B. bifidum FGZ30MM3 and their mixture on AAD in mice. The lincomycin hydrochloride-induced AAD models were gavaged with a single strain or a probiotic mixture for a short period to assess the changes in colonic histopathology and cytokine concentrations, intestinal epithelial permeability and integrity, short-chain fatty acids (SCFAs), and the diversity of intestinal microbiota. Our data indicated that both the sole use of Bacteroides and the combination of Bacteroides and Bifidobacterium beneficially weakened systemic inflammation, increased the recovery rate of tissue structures, increased the concentrations of SCFAs, and restored the gut microbiota. Moreover, the probiotic mixture was more effective than the single strain. Specifically, B. uniformis FGDLZ48B1 combined with the B. adolescentis FHNFQ48M5 group was more effective in alleviating the pathological features of the colon, downregulating the concentrations of interleukin (IL)-6, and upregulating the expression of occludin. In summary, our research suggests that administration of a mixture of B. uniformis FGDLZ48B1 and B. adolescentis FHNFQ48M5 is an effective approach for treating AAD.

Keywords: AAD; Bacteroides; Bifidobacterium; mice.

Figure 1

(A) Schematic diagram of the experimental design: (B) diarrhea status scores; and (C) water content in stool. *, **, ***, and **** indicate significant differences (p < 0.05, p < 0.01, p < 0.001, and p < 0.0001, respectively) between groups.

Figure 2

Histological examination of the representative image of H&E staining (scale bar = 100 µm). Yellow arrow—depletion of goblet cells; green arrow—mucosal edema; and black arrow—inflammatory cellular infiltration.

Figure 3

Analysis of cytokines in colon tissue by ELISA: (A) IL-6, (B) IL-17, (C) IL-1β, and (D) TNF-α. * and ** indicate significant differences (p < 0.05, p < 0.01 respectively) between groups.

Figure 4

ELISA analyses of (A) lipopolysaccharide (LPS). Real-time PCR analysis of (B) occludin, (C) Mucin-2, and (D) NHE3, mRNA expression normalized to β-actin in the colons. *, **, ***, and **** indicate significant differences (p < 0.05, p < 0.01, p < 0.001, and p < 0.0001, respectively) between groups.

Figure 5

Effects of different treatments on the concentrations of (A) propionic acid, (B) acetic acid, (C) isovaleric acid, and (D) isobutyric acid. *, **, ***, and **** indicate significant differences (p < 0.05, p < 0.01, p < 0.001, and p < 0.0001, respectively) between groups.

Figure 6

(A) Evenness index, (B) Shannon index, (C) principal coordinate analysis (PCoA), (D) clustering of distance based on the Jaccard index, and (E) correlation between the physiological and anti-inflammatory effects. *, **, ***, and **** indicate significant differences (p < 0.05, p < 0.01, p < 0.001, and p < 0.0001, respectively) between groups.