Antibiotic-associated diarrhea (AAD) is iatrogenic diarrhea characterized by disruption of the gut microbiota. Probiotics are routinely used to treat AAD in clinical practice; however, the effectiveness and mechanisms by which probiotics alleviate symptoms remain poorly understood. We previously isolated a non-toxic Bacteroides fragilis strain ZY-312, which has been verified to be beneficial in certain infection disorders. However, the precise role of this commensal bacterium in AAD is unknown. In this study, we successfully established an AAD rat model by exposing rats to appropriate antibiotics. These rats developed diarrhea symptoms and showed alterations in their intestinal microbiota, including overgrowth of some pathogenic bacteria. In addition, gastrointestinal barrier defects, indicated by compromised aquaporin expression, aberrant tight junction proteins, and decreased abundance of mucus-filled goblet cells, were also detected in ADD rats compared with control animals. Of note, oral treatment with B. fragilis strain ZY-312 ameliorated AAD-related diarrhea symptoms by increasing the abundance of specific commensal microbiota. Interestingly, we demonstrated that these changes were coincident with the restoration of intestinal barrier function and enterocyte regeneration in AAD rats. In summary, we identified a potential probiotic therapeutic strategy for AAD and identified the vital roles of B. fragilis strain ZY-312 in modulating the colonic bacterial community and participating in microbiota-mediated epithelial cell proliferation and differentiation.

Hepatic fibrosis is a physiological response to liver injury that includes a range of cell types. The pathogenesis of hepatic fibrosis currently focuses on hepatic stellate cell (HSC) activation into muscle fiber cells and fibroblasts. Baicalin is a flavone glycoside. It is the glucuronide of baicalein, which is extracted from the dried roots of Scutellaria baicalensis Georgi. Previous work focused on the anti-viral, -inflammatory and -tumor properties of baicalin. However, the potential anti-fibrotic effects and mechanisms of baicalin are not known. The present study demonstrated that baicalin influenced the activation, proliferation, apoptosis, invasion and migration of platelet-derived growth factor-BB-induced activated HSC-T6 cells in a dose-dependent manner. To investigate the anti-fibrotic effect of baicalin, a one-color micro (mi)RNA array and reverse transcription-quantitative polymerase chain reaction analyses were used. Results demonstrated that baicalin increased the expression of the miRNA, miR-3595. In addition, the inhibition of miR-3595 substantially reversed the anti-fibrotic effect of baicalin. The present data also suggested that miR-3595 negatively regulates the long-chain-fatty-acid-CoA ligase 4 (ACSL4). Furthermore, ACSL4 acted in a baicalin-dependent manner to exhibit anti-fibrotic effects. Taken together, it was concluded that baicalin induces miR-3595 expression that modulates the expression levels of ACSL4. To the best of our knowledge, the present study is the first to demonstrate that baicalin induces overexpression of human miR-3595, and subsequently decreases the expression of ACSL4, resulting in an anti-fibrotic effect.

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