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Gut Microbiota-Immune System Interactions during Acute Kidney Injury

Sanjeev Noel, Fuad Mohammad, James White, Kyungho Lee, Sepideh Gharaie and Hamid Rabb
Kidney360 March 2021, 2 (3) 528-531; DOI: https://doi.org/10.34067/KID.0006792020
Sanjeev Noel
1Department of Medicine, Johns Hopkins University, Baltimore, Maryland
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Fuad Mohammad
1Department of Medicine, Johns Hopkins University, Baltimore, Maryland
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James White
2Resphera Biosciences, Baltimore, Maryland
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Kyungho Lee
1Department of Medicine, Johns Hopkins University, Baltimore, Maryland
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Sepideh Gharaie
1Department of Medicine, Johns Hopkins University, Baltimore, Maryland
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Hamid Rabb
1Department of Medicine, Johns Hopkins University, Baltimore, Maryland
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    Figure 1.

    Renal ischemia-reperfusion injury (IRI) and cisplatin treatment change gut microbial populations. Under an approved animal protocol, AKI was induced in male, 8- to 10-week-old, C57BL/6 mice by 30 minutes of bilateral IRI or 30 mg/kg cisplatin (CP) injection. The gut microbiota was then studied at baseline (D0) and 72 hours (D3) post-AKI using 16S sequencing. (A) IRI and CP affected relative abundance of bacterial species belonging to the phyla Actinobacteria, Bacteroidetes, Firmicutes, Tenericutes, and Verrucomicrobia. (B) The vertical dot plots represent differential abundance testing between sham and CP mice or sham and IRI mice (x axis, fold change; size, base mean), showing distinct alterations in microbial populations at the family level. The genera identified on the y axis are those that were affected by AKI, using negative binomial testing. There were no significant operational taxonomic units with species-level information. (C and D) Dimensional analysis by Brey non-metric multidimensional scaling (NMDS) and α-diversity analysis using the Shannon index suggests the microbiome differentiates itself over time, depending on treatment. (E) Percentage change in Erysipelotrichaceae incertae sedis and Lactobacillus populations after IRI and CP-induced AKI. Timept, time point. NA, not available.

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    Figure 2.

    An overview of gut microbiota–immune cell interactions in the kidney affecting injury and repair processes after AKI. Gut microbiota produce short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate, that interact with multiple G protein–coupled receptors on kidney epithelial cells. Similar interactions are likely involved in immune cells that modulate their number, immune function, and metabolism in the kidney. Normal gut microbiota promote the anti-inflammatory milieu by increasing T helper 2 (Th2) cell, regulatory T (Treg) cell, and M2 macrophage populations that protect kidneys from AKI. However, AKI-induced dysbiosis and translocation of bacterial products across the leaky intestine promote a proinflammatory immune environment, such as increased Th1 cells, M1 macrophages, and activated dendritic cells (DCs). Activated DCs secrete proinflammatory cytokines, such as IL-12 and IL-6, and skew the differentiation of naive CD4 T cells and maturation of B cells. Th17-inducing bacteria may promote Th17 immunity via IL-17A/IL-17F induction, which may involve signaling mediated by the Toll-like receptor ligands. Additionally, IgA produced by plasma cells residing in the gut epithelium modulates response to colonization by specific commensal bacteria. SCFAs also regulate cytokine expression in T cells and generation of Treg cells through histone deacetylase inhibition. Therapeutic and supplemental use of pre-, pro-, and postbiotics could be helpful in normalizing bacterial composition in the gut and in protecting the kidneys from AKI. NKT, natural killer T cell.

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Kidney360: 2 (3)
Kidney360
Vol. 2, Issue 3
25 Mar 2021
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Gut Microbiota-Immune System Interactions during Acute Kidney Injury
Sanjeev Noel, Fuad Mohammad, James White, Kyungho Lee, Sepideh Gharaie, Hamid Rabb
Kidney360 Mar 2021, 2 (3) 528-531; DOI: 10.34067/KID.0006792020

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Gut Microbiota-Immune System Interactions during Acute Kidney Injury
Sanjeev Noel, Fuad Mohammad, James White, Kyungho Lee, Sepideh Gharaie, Hamid Rabb
Kidney360 Mar 2021, 2 (3) 528-531; DOI: 10.34067/KID.0006792020
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  • Article
    • Gut Microbiota–Kidney Crosstalk
    • Gut Microbiota, Amino Acids, Antibiotics, and AKI
    • Role of Gut Microbiota in Immune-System Development and Function
    • Mechanism of Gut Microbiota–Immune System Interactions
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More in this TOC Section

  • CRRT De-escalation
  • Considerations for COVID-19 immunization in ESRD
  • Standardizing diagnosis and management of AIN
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Keywords

  • acute kidney injury and ICU nephrology
  • acute kidney injury
  • basic science
  • cisplatin
  • dysbiosis
  • gastrointestinal microbiome
  • gut microbiota
  • immune system
  • ischemia reperfusion injury
  • transplantation

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