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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

Schematic overview of ceftriaxone treatment and FMT/BCT. (A) To establish the intestinal dysbiosis model, BALB/c mice were treated with ceftriaxone sodium for 7 days. After that, they were divided into 3 experimental groups: the spontaneous recovery group (SR), the fecal microbiota transplantation group (FMT), and the bacterial consortium transplantation group (BCT). The red vertical bars indicate sampling dates. The recovery of intestinal ecosystem was observed for 3 weeks. (B) Mean body weights, (C) Cecal index, and (D) The number of mice with diarrhea were investigated respectively. ***p < 0.001; *, FMT compared with SR, p < 0.05; Δ, BCT compared with FMT, p < 0.05.
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Figure 1: Schematic overview of ceftriaxone treatment and FMT/BCT. (A) To establish the intestinal dysbiosis model, BALB/c mice were treated with ceftriaxone sodium for 7 days. After that, they were divided into 3 experimental groups: the spontaneous recovery group (SR), the fecal microbiota transplantation group (FMT), and the bacterial consortium transplantation group (BCT). The red vertical bars indicate sampling dates. The recovery of intestinal ecosystem was observed for 3 weeks. (B) Mean body weights, (C) Cecal index, and (D) The number of mice with diarrhea were investigated respectively. ***p < 0.001; *, FMT compared with SR, p < 0.05; Δ, BCT compared with FMT, p < 0.05.

Mentions: The experimental design is shown in Figure 1A. During administration of ceftriaxone and over the course of recovery, there were no incidences of mortality, and no significant changes in body weight were observed (Figure 1B). Compared with control mice, the average size of the cecum in ceftriaxone-treated mice was clearly larger (Figure 1C, top), and the ratio of cecal weight to body weight, termed the cecal index, was significantly higher (Figure 1C, p = 0.002). After 7 days of ceftriaxone treatment, antibiotic-associated diarrhea was observed in several mice. The number of diarrheic mice did not reduce during the 3 days of transplantation, but instead increased continually. On day 10, the average number of mice with diarrhea in each group was 9, which was 30.00% of the total (Figure 1D). Symptoms of diarrhea subsequently eased such that on day 16, significant differences in the percentage of diarrheic mice were observed between the FMT/BCT groups and the SR group (p = 0.0213; p = 0.0036), and between the BCT group and the FMT group (p = 0.0381).


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)

Schematic overview of ceftriaxone treatment and FMT/BCT. (A) To establish the intestinal dysbiosis model, BALB/c mice were treated with ceftriaxone sodium for 7 days. After that, they were divided into 3 experimental groups: the spontaneous recovery group (SR), the fecal microbiota transplantation group (FMT), and the bacterial consortium transplantation group (BCT). The red vertical bars indicate sampling dates. The recovery of intestinal ecosystem was observed for 3 weeks. (B) Mean body weights, (C) Cecal index, and (D) The number of mice with diarrhea were investigated respectively. ***p < 0.001; *, FMT compared with SR, p < 0.05; Δ, BCT compared with FMT, p < 0.05.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: Schematic overview of ceftriaxone treatment and FMT/BCT. (A) To establish the intestinal dysbiosis model, BALB/c mice were treated with ceftriaxone sodium for 7 days. After that, they were divided into 3 experimental groups: the spontaneous recovery group (SR), the fecal microbiota transplantation group (FMT), and the bacterial consortium transplantation group (BCT). The red vertical bars indicate sampling dates. The recovery of intestinal ecosystem was observed for 3 weeks. (B) Mean body weights, (C) Cecal index, and (D) The number of mice with diarrhea were investigated respectively. ***p < 0.001; *, FMT compared with SR, p < 0.05; Δ, BCT compared with FMT, p < 0.05.
Mentions: The experimental design is shown in Figure 1A. During administration of ceftriaxone and over the course of recovery, there were no incidences of mortality, and no significant changes in body weight were observed (Figure 1B). Compared with control mice, the average size of the cecum in ceftriaxone-treated mice was clearly larger (Figure 1C, top), and the ratio of cecal weight to body weight, termed the cecal index, was significantly higher (Figure 1C, p = 0.002). After 7 days of ceftriaxone treatment, antibiotic-associated diarrhea was observed in several mice. The number of diarrheic mice did not reduce during the 3 days of transplantation, but instead increased continually. On day 10, the average number of mice with diarrhea in each group was 9, which was 30.00% of the total (Figure 1D). Symptoms of diarrhea subsequently eased such that on day 16, significant differences in the percentage of diarrheic mice were observed between the FMT/BCT groups and the SR group (p = 0.0213; p = 0.0036), and between the BCT group and the FMT group (p = 0.0381).

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