AUTHOR=Li Wenwen , Zhang Siyu , Wang Yanyan , Bian Hongsheng , Yu Shuang , Huang Lili , Ma Weiwei 

TITLE=Complex probiotics alleviate ampicillin-induced antibiotic-associated diarrhea in mice

JOURNAL=Frontiers in Microbiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1156058

DOI=10.3389/fmicb.2023.1156058

ISSN=1664-302X

ABSTRACT=<sec><title>Aim</title><p>Antibiotic-associated diarrhea (AAD) is a common side effect during antibiotic treatment, which can cause dysbacteriosis of the gut microbiota. Previous studies have shown beneficial effects in AAD treatment with <italic>Bifidobacterium lactis</italic> XLTG11, <italic>Lactobacillus casei</italic> Zhang, <italic>Lactobacillus plantarum</italic> CCFM8661, and <italic>Lactobacillus rhamnosus</italic> Probio-M9. However, no studies have been conducted on the immunomodulatory effects and protective intestinal barrier function of four complex probiotics. The aim of our study is to investigate the alleviation effects of complex probiotics on ampicillin-induced AAD.</p></sec><sec><title>Methods</title><p>Thirty-six BALB/c mice were randomly divided into six groups: normal control group (NC), model control group (MC), low-, medium-, and high-dose probiotics groups (LD, MD, and HD), and positive drug (Bifico, 1 × 10<sup>7</sup> cfu) control group (PDC; Bifico, also known as Bifidobacterium Triple Live Capsule, is composed of <italic>Bifidobacterium longum</italic>, <italic>Lactobacillus acidophilus</italic>, and <italic>Enterococcus faecalis</italic>). An AAD model was established by intragastric administration of ampicillin, by gavage of different doses of complex probiotics and Bifico. The weight gain, fecal water content, loose stool grade, intestinal permeability, total protein and albumin levels, intestinal barrier, cytokine levels, and gut microbiota were determined.</p></sec><sec><title>Results</title><p>The results showed that complex probiotics significantly decreased the fecal water content, loose stool grade, intestinal permeability, and ileum tissue damage. Their application increased the weight gain, SIgA, TP, and ALB levels. Additionally, complex probiotics significantly decreased the levels of pro-inflammatory cytokines and increased those of anti-inflammatory cytokines. Meanwhile, the mRNA expression levels of ZO-1, occludin, claudin-1, and MUC2 were significantly upregulated in the probiotic-treated group. Furthermore, the complex probiotics increased the gut microbiota diversity and modulated the changes in the gut microbiota composition caused by ampicillin. At the phylum level, the abundance of <italic>Proteobacteria</italic> in the HD group was lower than that in the MC group, whereas that of <italic>Bacteroidetes</italic> was higher. At the genus level, the abundances of <italic>Klebsiella</italic> and <italic>Parabacteroides</italic> in the HD group were lower, whereas those of <italic>Bacteroides</italic>, <italic>Muribaculaceae</italic>, and <italic>Lactobacillus</italic> were higher than those in the MC group. Moreover, Spearman’s correlation analysis also found that several specific gut microbiota were significantly correlated with AAD-related indicators.</p></sec><sec><title>Conclusion</title><p>We found that complex probiotics improved the diarrhea-related indexes, regulated gut microbiota composition and diversity, increased the expression levels of intestinal protective barrier-related genes, preserved the intestinal barrier function, and relieved inflammation and intestinal injury, thereby effectively improving AAD-associated symptoms.</p><p><fig position="float" id="fig6"><label>Graphical Abstract</label><graphic xlink:href="fmicb-14-1156058-g006.tif" xmlns:xlink="http://www.w3.org/1999/xlink" /></fig></p></sec>