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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

Post-FMT or BCT changes of the mechanical barriers in intestinal mucosa of different mice groups. (A) Representative patterns of HE-stained sections of distal ileum and proximal colon in mice after 1 week recovery. Magnification, ×200. The red arrows indicate inflammatory cell infiltration, or vascular dilatation and congestion. (B) Histological analysis was performed after 1 week recovery. **p < 0.001 compared with control. (C) TER of distal ileum in different mice groups detected after 1 week recovery, *, FMT compared with SR, p < 0.05. The X axes indicate days after ceftriaxone treatment. (D) The concentration of Muc2 in intestinal mucus of mice. *, FMT compared with SR, p < 0.05. All values are means ± SD of 5 mice per group. (E) Muc2 immunostaining in mouse distal ileum and proximal colon.
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Figure 5: Post-FMT or BCT changes of the mechanical barriers in intestinal mucosa of different mice groups. (A) Representative patterns of HE-stained sections of distal ileum and proximal colon in mice after 1 week recovery. Magnification, ×200. The red arrows indicate inflammatory cell infiltration, or vascular dilatation and congestion. (B) Histological analysis was performed after 1 week recovery. **p < 0.001 compared with control. (C) TER of distal ileum in different mice groups detected after 1 week recovery, *, FMT compared with SR, p < 0.05. The X axes indicate days after ceftriaxone treatment. (D) The concentration of Muc2 in intestinal mucus of mice. *, FMT compared with SR, p < 0.05. All values are means ± SD of 5 mice per group. (E) Muc2 immunostaining in mouse distal ileum and proximal colon.

Mentions: Histological examination after 1 week of recovery showed that there were still lesions and inflammatory cells infiltration in distal ileum of the antibiotic treated mice (Figure 5A, top), distorted tissue architecture and vascular congestion were also detected (Figure 5A, bottom). While the destruction of the mucosae appeared to have been substantially ameliorated in mice receiving FMT or BCT, as less inflammatory cells infiltration, and less distorted tissue architecture and vascular congestion were detected, but these were not statistically significant according to the histological evaluation (Figure 5B, SR vs. FMT/BCT, all p > 0.05). After 2 weeks, the mucosae in the three different treatment groups had recovered to the level of the control group (Figures S4, S5). The intestinal mucosal permeability of mice decreased gradually during the recovery period (Figure 5C). Compared with the SR group, the mucosal permeability of mice in the FMT and BCT groups was significantly lower after 1 (p = 0.0483, p = 0.0465) and 2 (p = 0.0384, p = 0.0228) weeks of recovery.


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)

Post-FMT or BCT changes of the mechanical barriers in intestinal mucosa of different mice groups. (A) Representative patterns of HE-stained sections of distal ileum and proximal colon in mice after 1 week recovery. Magnification, ×200. The red arrows indicate inflammatory cell infiltration, or vascular dilatation and congestion. (B) Histological analysis was performed after 1 week recovery. **p < 0.001 compared with control. (C) TER of distal ileum in different mice groups detected after 1 week recovery, *, FMT compared with SR, p < 0.05. The X axes indicate days after ceftriaxone treatment. (D) The concentration of Muc2 in intestinal mucus of mice. *, FMT compared with SR, p < 0.05. All values are means ± SD of 5 mice per group. (E) Muc2 immunostaining in mouse distal ileum and proximal colon.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 5: Post-FMT or BCT changes of the mechanical barriers in intestinal mucosa of different mice groups. (A) Representative patterns of HE-stained sections of distal ileum and proximal colon in mice after 1 week recovery. Magnification, ×200. The red arrows indicate inflammatory cell infiltration, or vascular dilatation and congestion. (B) Histological analysis was performed after 1 week recovery. **p < 0.001 compared with control. (C) TER of distal ileum in different mice groups detected after 1 week recovery, *, FMT compared with SR, p < 0.05. The X axes indicate days after ceftriaxone treatment. (D) The concentration of Muc2 in intestinal mucus of mice. *, FMT compared with SR, p < 0.05. All values are means ± SD of 5 mice per group. (E) Muc2 immunostaining in mouse distal ileum and proximal colon.
Mentions: Histological examination after 1 week of recovery showed that there were still lesions and inflammatory cells infiltration in distal ileum of the antibiotic treated mice (Figure 5A, top), distorted tissue architecture and vascular congestion were also detected (Figure 5A, bottom). While the destruction of the mucosae appeared to have been substantially ameliorated in mice receiving FMT or BCT, as less inflammatory cells infiltration, and less distorted tissue architecture and vascular congestion were detected, but these were not statistically significant according to the histological evaluation (Figure 5B, SR vs. FMT/BCT, all p > 0.05). After 2 weeks, the mucosae in the three different treatment groups had recovered to the level of the control group (Figures S4, S5). The intestinal mucosal permeability of mice decreased gradually during the recovery period (Figure 5C). Compared with the SR group, the mucosal permeability of mice in the FMT and BCT groups was significantly lower after 1 (p = 0.0483, p = 0.0465) and 2 (p = 0.0384, p = 0.0228) weeks of recovery.

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