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Fecal microbiota transplantation and bacterial consortium transplantation have comparable effects on the re-establishment of mucosal barrier function in mice with intestinal dysbiosis.

Li M, Liang P, Li Z, Wang Y, Zhang G, Gao H, Wen S, Tang L - Front Microbiol (2015)

Bottom Line: 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.The effects of BCT are comparable to that of FMT, especially in normalizing the intestinal levels of Muc2, SIgA, and defensins.

View Article: PubMed Central - PubMed

Affiliation: Department of Microecology, School of Basic Medical Science, Dalian Medical University Dalian, China ; Key Microecology Laboratory of Liaoning Province Dalian, China.

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.

No MeSH data available.


Related in: MedlinePlus

The intestinal phenotype of ceftriaxone-treated mice. (A) Representative patterns of HE-stained sections of distal ileum and colon in mice. Magnification, ×200. The red arrows indicate inflammatory cell infiltration, or vascular dilatation and congestion. (B) Histological evaluation of the HE-stained sections. (C) Trans-epithelial resistance (TER) of mouse distal ileum and colon was determined by measuring the average changes in potential difference in response to 3 μA current generated across the tissue segments every 6 s for 30 min. (D) Muc2 immunostaining in mouse distal ileum (top) and proximal colon (bottom), Magnification, ×200. (E) The concentration of Muc2 in intestinal mucus of mice. (F) The concentration of SIgA in intestinal mucus and serum IgA of mice. (G) The concentration of defensins in intestinal mucus of mice. (H) Serum levels of IL1-ß, IL-6, and TNF-α in mice. *p < 0.05; ***p < 0.001. All the samples were taken at day 8.
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Figure 3: The intestinal phenotype of ceftriaxone-treated mice. (A) Representative patterns of HE-stained sections of distal ileum and colon in mice. Magnification, ×200. The red arrows indicate inflammatory cell infiltration, or vascular dilatation and congestion. (B) Histological evaluation of the HE-stained sections. (C) Trans-epithelial resistance (TER) of mouse distal ileum and colon was determined by measuring the average changes in potential difference in response to 3 μA current generated across the tissue segments every 6 s for 30 min. (D) Muc2 immunostaining in mouse distal ileum (top) and proximal colon (bottom), Magnification, ×200. (E) The concentration of Muc2 in intestinal mucus of mice. (F) The concentration of SIgA in intestinal mucus and serum IgA of mice. (G) The concentration of defensins in intestinal mucus of mice. (H) Serum levels of IL1-ß, IL-6, and TNF-α in mice. *p < 0.05; ***p < 0.001. All the samples were taken at day 8.

Mentions: After sectioning and HE staining, ileum and colon samples were observed under a microscope. Lesions and inflammatory cells infiltration were observed in the ileum of ceftriaxone-treated mice (Figure 3A, top). The integrity of microvilli in the ileum of ceftriaxone-treated mice was perturbed, they arranged irregularly, and in some instances were desquamated, and the local membrane of the intestinal mucosal epithelial cell is not complete (Figure S3). The ceftriaxone-treated mice had an increase in hyperplasia of the colonic mucosa and distorted tissue architecture; they had more severe vascular dilatation and congestion than that of control mice (Figure 3A, bottom). The histological score (Figure 3B) of both the ileum and colon in mice treated with ceftriaxone was higher compared with control mice.


Fecal microbiota transplantation and bacterial consortium transplantation have comparable effects on the re-establishment of mucosal barrier function in mice with intestinal dysbiosis.

Li M, Liang P, Li Z, Wang Y, Zhang G, Gao H, Wen S, Tang L - Front Microbiol (2015)

The intestinal phenotype of ceftriaxone-treated mice. (A) Representative patterns of HE-stained sections of distal ileum and colon in mice. Magnification, ×200. The red arrows indicate inflammatory cell infiltration, or vascular dilatation and congestion. (B) Histological evaluation of the HE-stained sections. (C) Trans-epithelial resistance (TER) of mouse distal ileum and colon was determined by measuring the average changes in potential difference in response to 3 μA current generated across the tissue segments every 6 s for 30 min. (D) Muc2 immunostaining in mouse distal ileum (top) and proximal colon (bottom), Magnification, ×200. (E) The concentration of Muc2 in intestinal mucus of mice. (F) The concentration of SIgA in intestinal mucus and serum IgA of mice. (G) The concentration of defensins in intestinal mucus of mice. (H) Serum levels of IL1-ß, IL-6, and TNF-α in mice. *p < 0.05; ***p < 0.001. All the samples were taken at day 8.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493656&req=5

Figure 3: The intestinal phenotype of ceftriaxone-treated mice. (A) Representative patterns of HE-stained sections of distal ileum and colon in mice. Magnification, ×200. The red arrows indicate inflammatory cell infiltration, or vascular dilatation and congestion. (B) Histological evaluation of the HE-stained sections. (C) Trans-epithelial resistance (TER) of mouse distal ileum and colon was determined by measuring the average changes in potential difference in response to 3 μA current generated across the tissue segments every 6 s for 30 min. (D) Muc2 immunostaining in mouse distal ileum (top) and proximal colon (bottom), Magnification, ×200. (E) The concentration of Muc2 in intestinal mucus of mice. (F) The concentration of SIgA in intestinal mucus and serum IgA of mice. (G) The concentration of defensins in intestinal mucus of mice. (H) Serum levels of IL1-ß, IL-6, and TNF-α in mice. *p < 0.05; ***p < 0.001. All the samples were taken at day 8.
Mentions: After sectioning and HE staining, ileum and colon samples were observed under a microscope. Lesions and inflammatory cells infiltration were observed in the ileum of ceftriaxone-treated mice (Figure 3A, top). The integrity of microvilli in the ileum of ceftriaxone-treated mice was perturbed, they arranged irregularly, and in some instances were desquamated, and the local membrane of the intestinal mucosal epithelial cell is not complete (Figure S3). The ceftriaxone-treated mice had an increase in hyperplasia of the colonic mucosa and distorted tissue architecture; they had more severe vascular dilatation and congestion than that of control mice (Figure 3A, bottom). The histological score (Figure 3B) of both the ileum and colon in mice treated with ceftriaxone was higher compared with control mice.

Bottom Line: 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.The effects of BCT are comparable to that of FMT, especially in normalizing the intestinal levels of Muc2, SIgA, and defensins.

View Article: PubMed Central - PubMed

Affiliation: Department of Microecology, School of Basic Medical Science, Dalian Medical University Dalian, China ; Key Microecology Laboratory of Liaoning Province Dalian, China.

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.

No MeSH data available.


Related in: MedlinePlus