Dataset Information

Effects of Fecal Microbiota Transplantation on Composition in Mice with CKD.

ABSTRACT:

Background

Chronic kidney disease (CKD) is a renal disorder characterized by the accumulation of uremic toxins with limited strategies to reduce their concentrations. A large amount of data supports the pivotal role of intestinal microbiota in CKD complications and as a major source of uremic toxins production. Here, we explored whether fecal microbiota transplantation (FMT) could be attenuated in metabolic complication and uremic toxin accumulation in mice with CKD.

Methods

Kidney failure was chemically induced by a diet containing 0.25% (w/w) of adenine for four weeks. Mice were randomized into three groups: control, CKD and CKD + FMT groups. After four weeks, CKD mice underwent fecal microbiota transplantation (FMT) from healthy mice or phosphate buffered saline as control. The gut microbiota structure, uremic toxins plasmatic concentrations, and metabolic profiles were explored three weeks after transplantation.

Results

Associated with the increase of alpha diversity, we observed a noticeable improvement of gut microbiota disturbance, after FMT treatment. FMT further decreased p-cresyl sulfate accumulation and improved glucose tolerance. There was no change in kidney function.

Conclusions

These data indicate that FMT limited the accumulation of uremic toxins issued from intestinal cresol pathway by a beneficial effect on gut microbiota diversity. Further studies are needed to investigate the FMT efficiency, the timing and feces amount for the transplantation before, to become a therapeutic option in CKD patients.

SUBMITTER: Barba C

PROVIDER: S-EPMC7761367 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Publications

Effects of Fecal Microbiota Transplantation on Composition in Mice with CKD.

Barba Christophe C Soulage Christophe O CO Caggiano Gianvito G Glorieux Griet G Fouque Denis D Koppe Laetitia L

Toxins 20201124 12

<h4>Background</h4>Chronic kidney disease (CKD) is a renal disorder characterized by the accumulation of uremic toxins with limited strategies to reduce their concentrations. A large amount of data supports the pivotal role of intestinal microbiota in CKD complications and as a major source of uremic toxins production. Here, we explored whether fecal microbiota transplantation (FMT) could be attenuated in metabolic complication and uremic toxin accumulation in mice with CKD.<h4>Methods</h4>Kidne ...[more]

PMID: 33255454

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Project description:This study was conducted to investigate the effect of fecal microbiota transplantation (FMT) from yaks on weaning diarrhea, fecal microbiota composition, microbial network structure and functional pathways in Chinese Holstein Calves. In this study, 50 calves were randomly divided into five groups of 10 each: NC group (no supplementation), Control group (normal saline), low concentration FMT group (LFMT, 1 × 108 CFU/ml), high concentration FMT group (HMFT, 1 × 109 CFU/ml), and sterilized FMT group (SMFT, sterilized bacterial solution). The test lasted for 30 days. We found that FMT reduced the incidence of diarrhea in weaned calves, and the anti-diarrhea effect of LFMT was stronger than those of HFMT and SFMT. Calf feces were collected by rectal palpation on days 5, 10, 15, and 20 post-weaning, and high-throughput sequencing of bacterial 16S rRNA and fungal internal transcribed spacer region of fecal microbiota was performed. We observed that the richness and diversity of bacterial microbiota in the LFMT, HFMT, and SFMT groups were higher than those in the NC and Control groups at day 20 after weaning. The treatment had a significant effect on bacterial richness (p < 0.05), but not on fungal diversity or richness. The analysis of gut microbiome showed that Firmicutes and Bacteroides were the main bacterial phyla in the feces of weaned calves, and norank_ f Muribaculaceae, UCG-005, Rikenellaceae_RC9_gut_group, Bacteroides, and Blautia were the main genera. Ascomycota and Basidiomycota were the main fungal phyla. Compared to abundance parameters in the Control and NC groups, relative abundances of Firmicutes in the FMT groups increased at different time points after weaning. The relative abundance of Blautia and Lactobacillus in the LFMT group increased significantly after weaning. In addition, abundances of Ruminococcus and Romboutsia, which produce short-chain fatty acids, were also increased in different FMT groups. FMT significantly increased the relative abundance of beneficial bacteria, enhanced the complexity of the fecal microbial network, and promoted important metabolic and cellular processes in weaned calves. In conclusion, our study provides a reference and theoretical basis for FMT to prevent calf weaning diarrhea and other intestinal diseases in ruminants.

Project description:Chronic kidney disease (CKD) is associated with gut microbiome dysbiosis, but the role of intestinal flora in CKD treatment remains to be elucidated. Fecal microbiota transplantation (FMT) can be utilized to re-establish healthy gut microbiota for a variety of diseases, which offers new insight for treating CKD. First, 5/6 nephrectomy rats (Donor CKD) and sham rats (Donor Sham) were used as donors for FMT, and fecal metagenome were analyzed to explore potential therapeutic targets. Then, to assess the effect of FMT on CKD, sterilized 1/2 nephrectomy rats were transplanted with fecal microbiota from Donor sham (CKD/Sham) or Donor CKD (CKD/CKD) rats, and 1/2 nephrectomy rats without FMT (CKD) or no nephrectomy (Sham) were used as model control or normal control. Results showed that Bacteroides uniformis and Anaerotruncus sp. 1XD22-93 were enriched in Donor CKD, while Lactobacillus johnsonii and Lactobacillus intestinalis were reduced. In addition, the increased abundance of microbial functions included tryptophan metabolism and lysine degradation contributing to the accumulation of protein-bound uremic toxins (PBUTs) in Donor CKD. Genome analysis indicated that FMT successfully differentiated groups of gut microbes and altered specific gut microbiota after 1 week of treatment, with Bacteroides uniformis and Anaerotruncus sp. 1XD22-93 increasing in CKD/CKD group as well as Lactobacillus johnsonii and Lactobacillus intestinalis being improved in CKD/Sham group. In comparison to CKD group, substantial PBUT buildup and renal damage were observed in CKD/CKD. Interestingly, compared to CKD or CKD/CKD group, tryptophan metabolism and lysine degradation were efficiently suppressed in CKD/Sham group, while lysine biosynthesis was promoted. Therefore, FMT considerably reduced PBUTs accumulation. After FMT, PBUTs and renal function in CKD/Sham rats remained the same as in Sham group throughout the experimental period. In summary, FMT could delay the malignant development of CKD by modifying microbial amino acid metabolism through altering the microenvironment of intestinal flora, thereby providing a novel potential approach for treating CKD.

Dataset Information

Effects of Fecal Microbiota Transplantation on Composition in Mice with CKD.

Background

Methods

Results

Conclusions

Publications

Effects of Fecal Microbiota Transplantation on Composition in Mice with CKD.

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