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Translocated microbiome composition determines immunological outcome in treated HIV infection.

Cell | 2021

The impact of the microbiome on HIV disease is widely acknowledged although the mechanisms downstream of fluctuations in microbial composition remain speculative. We detected rapid, dynamic changes in translocated microbial constituents during two years after cART initiation. An unbiased systems biology approach revealed two distinct pathways driven by changes in the abundance ratio of Serratia to other bacterial genera. Increased CD4 T cell numbers over the first year were associated with high Serratia abundance, pro-inflammatory innate cytokines, and metabolites that drive Th17 gene expression signatures and restoration of mucosal integrity. Subsequently, decreased Serratia abundance and downregulation of innate cytokines allowed re-establishment of systemic T cell homeostasis promoting restoration of Th1 and Th2 gene expression signatures. Analyses of three other geographically distinct cohorts of treated HIV infection established a more generalized principle that changes in diversity and composition of translocated microbial species influence systemic inflammation and consequently CD4 T cell recovery.

Pubmed ID: 34237254 RIS Download

Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: R37 AI141258
  • Agency: NIDA NIH HHS, United States
    Id: R01 DA043263
  • Agency: NIDA NIH HHS, United States
    Id: R01 DA042712
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI124965
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL092565
  • Agency: NIAID NIH HHS, United States
    Id: P01 AI074340
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK112254
  • Agency: NIAID NIH HHS, United States
    Id: P30 AI036219
  • Agency: NIAID NIH HHS, United States
    Id: U01 AI141981

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This is a list of tools and resources that we have found mentioned in this publication.


HTSeq (tool)

RRID:SCR_005514

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RRID:SCR_006751

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RRID:SCR_010233

American company incorporated that develops, manufactures and markets integrated systems for the analysis of genetic variation and biological function. Provides a line of products and services that serve the sequencing, genotyping and gene expression and proteomics markets. Its headquarters are located in San Diego, California.

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RRID:SCR_010943

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RRID:SCR_011848

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RRID:SCR_012802

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RRID:SCR_013575

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RRID:SCR_016955

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