Abstract
Fecal microbiota transplantation (FMT) is a promising therapy, despite some reports of adverse side effects. Bacterial consortia transplantation (BCT) for targeted restoration of the intestinal ecosystem is considered a relatively safe and simple procedure. However, no systematic research has assessed the effects of FMT and BCT on immune responses of intestinal mucosal barrier in patients. We conducted complementary studies in animal models on the effects of FMT and BCT, and provide recommendations for improving the clinical outcomes of these treatments. To establish the dysbiosis model, male BALB/c mice were treated with ceftriaxone intra-gastrically for 7 days. After that, FMT and BCT were performed on ceftriaxone-treated mice for 3 consecutive days to rebuild the intestinal ecosystem. Post-FMT and post-BCT changes of the intestinal microbial community and mucosal barrier functions were investigated and compared. Disruption of intestinal microbial homeostasis impacted the integrity of mucosal epithelial layer, resulting in increased intestinal permeability. These outcomes were accompanied by overexpression of Muc2, significant decrease of SIgA secretion, and overproduction of defensins and inflammatory cytokines. After FMT and BCT, the intestinal microbiota recovered quickly, this was associated with better reconstruction of mucosal barriers and re-establishment of immune networks compared with spontaneous recovery (SR). Although based on a short-term study, our results suggest that FMT and BCT promote the re-establishment of intestinal microbial communities in mice with antibiotic-induced dysbiosis, and contribute to the temporal and spatial interactions between microbiota and mucosal barriers. The effects of BCT are comparable to that of FMT, especially in normalizing the intestinal levels of Muc2, SIgA, and defensins.
Highlights
Commensal bacteria living in the human gastrointestinal tract provide a biological barrier against the invasion of pathogens and contribute to the modulation of the immune system (Hooper et al, 2012; Maynard et al, 2012)
After 7 days of ceftriaxone treatment, antibiotic-associated diarrhea was observed in several mice
Our study demonstrated that intragastric ceftriaxone induced severe dysbiosis in mice, and both the population and diversity of microbes were disturbed in the cecum of antibiotic-treated mice
Summary
Commensal bacteria living in the human gastrointestinal tract provide a biological barrier against the invasion of pathogens and contribute to the modulation of the immune system (Hooper et al, 2012; Maynard et al, 2012). Several studies have reported that infusion of fecal suspension from healthy individuals to inflammatory bowel disease (IBD) (Bennet and Brinkman, 1989; Kunde et al, 2013; Kao et al, 2014) or irritable bowel syndrome (IBS) (Konig and Brummer, 2014; Shanahan and Quigley, 2014) patients resulted in clinical improvement and remission It has been suggested by many scientists that FMT has promising therapeutic potential for the treatment of diabetes (Udayappan et al, 2014), obesity, non-alcoholic fatty liver disease (NAFLD), and even cardiovascular disease (Smits et al, 2013). Complementary studies of post-FMT or postBCT changes in animal models are important to improve clinical efficacy
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