Zhang, Wanying
(Department of Clinical Laboratory, Fourth Affiliated Hospital of Harbin Medical University)
,
Zou, Guiling
(Department of Clinical Laboratory, Fourth Affiliated Hospital of Harbin Medical University)
,
Li, Bin
(Department of Clinical Laboratory, Fourth Affiliated Hospital of Harbin Medical University)
,
Du, Xuefei
(Department of Clinical Laboratory, Fourth Affiliated Hospital of Harbin Medical University)
,
Sun, Zhe
(Department of Clinical Laboratory, Fourth Affiliated Hospital of Harbin Medical University)
,
Sun, Yu
(Department of Clinical Laboratory, Fourth Affiliated Hospital of Harbin Medical University)
,
Jiang, Xiaofeng
(Department of Clinical Laboratory, Fourth Affiliated Hospital of Harbin Medical University)
Inflammatory bowel disease (IBD) is an increasing global burden and a predisposing factor to colorectal cancer. Although a number of treatment options are available, the side effects could be considerable. Studies on fecal microbiota transplantation (FMT) as an IBD intervention protocol require furt...
Inflammatory bowel disease (IBD) is an increasing global burden and a predisposing factor to colorectal cancer. Although a number of treatment options are available, the side effects could be considerable. Studies on fecal microbiota transplantation (FMT) as an IBD intervention protocol require further validation as the underlying mechanisms for its attenuating effects remain unclear. This study aims to demonstrate the ameliorative role of FMT in an ulcerative colitis (UC) model induced by dextran sulfate sodium (DSS) and elucidate its relative mechanisms in a mouse model. It was shown that FMT intervention decreased disease activity index (DAI) levels and increased the body weight, colon weight and colon length of experimental animals. It also alleviated histopathological changes, reduced key cytokine expression and oxidative status in the colon. A down-regulated expression level of genes associated with NF-κB signaling pathway was also observed. The results of 16S rRNA gene sequencing showed that FMT intervention restored the gut microbiota to the pattern of the control group by increasing the relative abundance of Firmicutes and decreasing the abundances of Bacteroidetes and Proteobacteria. The relative abundances of the genera Lactobacillus, Butyricicoccus, Lachnoclostridium, Olsenella and Odoribacter were upregulated but Helicobacter, Bacteroides and Clostridium were reduced after FMT administration. Furthermore, FMT administration elevated the concentrations of SCFAs in the colon. In conclusion, FMT intervention could be suitable for UC control, but further validations via clinical trials are recommended.
Inflammatory bowel disease (IBD) is an increasing global burden and a predisposing factor to colorectal cancer. Although a number of treatment options are available, the side effects could be considerable. Studies on fecal microbiota transplantation (FMT) as an IBD intervention protocol require further validation as the underlying mechanisms for its attenuating effects remain unclear. This study aims to demonstrate the ameliorative role of FMT in an ulcerative colitis (UC) model induced by dextran sulfate sodium (DSS) and elucidate its relative mechanisms in a mouse model. It was shown that FMT intervention decreased disease activity index (DAI) levels and increased the body weight, colon weight and colon length of experimental animals. It also alleviated histopathological changes, reduced key cytokine expression and oxidative status in the colon. A down-regulated expression level of genes associated with NF-κB signaling pathway was also observed. The results of 16S rRNA gene sequencing showed that FMT intervention restored the gut microbiota to the pattern of the control group by increasing the relative abundance of Firmicutes and decreasing the abundances of Bacteroidetes and Proteobacteria. The relative abundances of the genera Lactobacillus, Butyricicoccus, Lachnoclostridium, Olsenella and Odoribacter were upregulated but Helicobacter, Bacteroides and Clostridium were reduced after FMT administration. Furthermore, FMT administration elevated the concentrations of SCFAs in the colon. In conclusion, FMT intervention could be suitable for UC control, but further validations via clinical trials are recommended.
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제안 방법
FMT administration was performed by gavage with 200 μl of the supernatant from the fecal sample once a day for a period of 2 weeks in the FMT group.
In this study, the taxonomic composition of the microbiomes of the control, FMT and DSS groups was also carried out. The microbiota in samples analyzed from all studied groups were made up of Bacteriodetes, Firmicutes and Proteobacteria phyla.
Therefore, interventions that modulate the production of inflammatory cytokines can be promising therapeutic applications for colitis treatment. To evaluate the influence of FMT on cytokine expression in the UC mice induced by DSS, mRNA expression of pro-inflammatory cytokines was determined. As shown in Fig.
대상 데이터
A total of 36 female BALB/c mice (7 weeks old, 18-20 g weight) were purchased from the Vital River Laboratory Animal Technology Company (China) and raised at the Harbin Medical University Animal Center. Male mice were not used as their potential aggressiveness could constitute an uncontrolled variable in group-housed male mice.
데이터처리
In addition, all obtained data are expressed as the mean ± standard deviation (SD), with statistical significance analyzed using one-way ANOVA followed by a Duncan' test.
이론/모형
Homogenate was centrifuged at 12,000 g at 4°C for 15 min to obtain total protein and its concentrations were measured with the bicinchoninic acid protein assay (BCA, Beyotime, China) method.
성능/효과
After FMT intervention, the levels of CAT, SOD and T-AOC significantly increased (p < 0.05) and the level of MDA decreased (p < 0.01), implying that FMT intervention could effectively ameliorate oxidative stress.
These results indicated that FMT intervention regulated gut microbiota and their metabolites, such as SCFAs, which could attenuate UC conditions through NF-κB signaling pathway inhibition.
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