Limits...
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

Ceftriaxone induced intestinal dysbiosis in mice. (A) DGGE pattern of the cecal microbial community of mice. C1–C3, control mice, D1–D3, dysbiosis mice. a–c, the bands differ from control were extracted from the DGGE gel and sequenced. (B) PCA of the DGGE profile. Community similarity was calculated using the weighted UniFrac distance metric, which incorporates phylogenetic as well as relative abundance information. PC1 and PC2 account for 76.70% of the variation. White dots, healthy mice; red dots, ceftriaxone-treated mice. (C) The total population of intestinal microbes in control and ceftriaxone-treated mice detected by qPCR. (D) The population of selected commensal bacteria in control and ceftriaxone-treated mice detected by qPCR. *p < 0.05; **p < 0.01; ***p < 0.001.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4493656&req=5

Figure 2: Ceftriaxone induced intestinal dysbiosis in mice. (A) DGGE pattern of the cecal microbial community of mice. C1–C3, control mice, D1–D3, dysbiosis mice. a–c, the bands differ from control were extracted from the DGGE gel and sequenced. (B) PCA of the DGGE profile. Community similarity was calculated using the weighted UniFrac distance metric, which incorporates phylogenetic as well as relative abundance information. PC1 and PC2 account for 76.70% of the variation. White dots, healthy mice; red dots, ceftriaxone-treated mice. (C) The total population of intestinal microbes in control and ceftriaxone-treated mice detected by qPCR. (D) The population of selected commensal bacteria in control and ceftriaxone-treated mice detected by qPCR. *p < 0.05; **p < 0.01; ***p < 0.001.

Mentions: DGGE fingerprinting of cecal bacteria indicated a significant decrease of microbial diversity in ceftriaxone-treated mice. The number of bands was reduced dramatically from 27.004 ± 1.000 to 7.667 ± 0.333 (Figure 2A, p = 0.0001). The data resulting from DGGE analysis were subjected to PCA. Figure 2B shows that distinct intestinal microbiota profiles are present in the control mice and the ceftriaxone-treated mice. Samples taken at day 8, right after the 7-day's ceftriaxone administration, were typically of the same group (D1, D2, D3), in contrast to samples from the control mice (C1, C2, C3) which were treated sterile water. The Log number of total bacteria per gram of cecum content as assessed by q-PCR decreased from 10.942 ± 0.125 to 10.116 ± 0.070 (Figure 2C, p = 0.0049). Contrary to the decreasing pattern of overall bacterial population, several bands in the antibiotic-treated samples were more prominent (Figure 2A, a–c). Sequence analysis of 16S rRNA gene fragments of these bands revealed that a and b belonged to the genus Enterococcus, and c showed highest similarity to Clostridium species (Figure S2).


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)

Ceftriaxone induced intestinal dysbiosis in mice. (A) DGGE pattern of the cecal microbial community of mice. C1–C3, control mice, D1–D3, dysbiosis mice. a–c, the bands differ from control were extracted from the DGGE gel and sequenced. (B) PCA of the DGGE profile. Community similarity was calculated using the weighted UniFrac distance metric, which incorporates phylogenetic as well as relative abundance information. PC1 and PC2 account for 76.70% of the variation. White dots, healthy mice; red dots, ceftriaxone-treated mice. (C) The total population of intestinal microbes in control and ceftriaxone-treated mice detected by qPCR. (D) The population of selected commensal bacteria in control and ceftriaxone-treated mice detected by qPCR. *p < 0.05; **p < 0.01; ***p < 0.001.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 2: Ceftriaxone induced intestinal dysbiosis in mice. (A) DGGE pattern of the cecal microbial community of mice. C1–C3, control mice, D1–D3, dysbiosis mice. a–c, the bands differ from control were extracted from the DGGE gel and sequenced. (B) PCA of the DGGE profile. Community similarity was calculated using the weighted UniFrac distance metric, which incorporates phylogenetic as well as relative abundance information. PC1 and PC2 account for 76.70% of the variation. White dots, healthy mice; red dots, ceftriaxone-treated mice. (C) The total population of intestinal microbes in control and ceftriaxone-treated mice detected by qPCR. (D) The population of selected commensal bacteria in control and ceftriaxone-treated mice detected by qPCR. *p < 0.05; **p < 0.01; ***p < 0.001.
Mentions: DGGE fingerprinting of cecal bacteria indicated a significant decrease of microbial diversity in ceftriaxone-treated mice. The number of bands was reduced dramatically from 27.004 ± 1.000 to 7.667 ± 0.333 (Figure 2A, p = 0.0001). The data resulting from DGGE analysis were subjected to PCA. Figure 2B shows that distinct intestinal microbiota profiles are present in the control mice and the ceftriaxone-treated mice. Samples taken at day 8, right after the 7-day's ceftriaxone administration, were typically of the same group (D1, D2, D3), in contrast to samples from the control mice (C1, C2, C3) which were treated sterile water. The Log number of total bacteria per gram of cecum content as assessed by q-PCR decreased from 10.942 ± 0.125 to 10.116 ± 0.070 (Figure 2C, p = 0.0049). Contrary to the decreasing pattern of overall bacterial population, several bands in the antibiotic-treated samples were more prominent (Figure 2A, a–c). Sequence analysis of 16S rRNA gene fragments of these bands revealed that a and b belonged to the genus Enterococcus, and c showed highest similarity to Clostridium species (Figure S2).

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