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An orally delivered microbial cocktail for the removal of nitrogenous metabolic waste in animal models of kidney failure

Abstract

Patients with kidney failure commonly require dialysis to remove nitrogenous wastes and to reduce burden to the kidney. Here, we show that a bacterial cocktail orally delivered in animals with kidney injury can metabolize blood nitrogenous waste products before they diffuse through the intestinal mucosal barrier. The microbial cocktail consists of three strains of bacteria isolated from faecal microbiota that metabolize urea and creatinine into amino acids, and is encapsulated in calcium alginate microspheres coated with a polydopamine layer that is selectively permeable to small-molecule nitrogenous wastes. In murine models of acute kidney injury and chronic kidney failure, and in porcine kidney failure models, the encapsulated microbial cocktail significantly reduced urea and creatinine concentrations in blood, and did not lead to any adverse effects.

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Fig. 1: Screening of bacteria with cascaded metabolic reactions.
Fig. 2: Construction of the BME.
Fig. 3: In vivo therapeutic effect of the BME in murine and porcine AKI models.
Fig. 4: In vivo therapeutic effect of the BME in a murine CKF model.

Data availability

The main data supporting the results of this study are available within the paper and its Supplementary Information. The raw and analysed datasets generated during this study are too large to be publicly shared, yet they are available for research purposes from the corresponding authors on reasonable request.

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Acknowledgements

This work was supported by the National Key Research and Development Program of China (2019YFA0905603) and National Natural Science Foundation of China (51988102, 51833007, 51690152, 51573142 and 21721005).

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Contributions

D.-W.Z. and X.-Z.Z. conceived the project and designed the experiments. P.P. and K.-W.C. synthesized the materials. P.P. and K.-W.C. performed the in vitro microbiological experiments. D.-W.Z., P.P., J.-X.F. and H.C. collected and analysed the data. P.P. and K.-W.C. performed the in vivo experiments. D.-W.Z., P.P., C.-X.L., H.C. and X.-Z.Z. co-wrote the manuscript. All authors discussed the results and reviewed the manuscript.

Corresponding author

Correspondence to Xian-Zheng Zhang.

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Supplementary Information

Supplementary methods, Figs.1–8 and Table 1.

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Zheng, DW., Pan, P., Chen, KW. et al. An orally delivered microbial cocktail for the removal of nitrogenous metabolic waste in animal models of kidney failure. Nat Biomed Eng 4, 853–862 (2020). https://doi.org/10.1038/s41551-020-0582-1

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