Molecular patterns of microbial and metabolic interactions in septic patients with persistent lymphopenia

Abstract

Background

Persistent lymphopenia can be regarded as an important index of acquired immune dysfunction in sepsis. Whether the specific immune factor changes in septic patients with lymphopenia and the correlation to gut microbiota and metabolites remain unclear.

Methods

This single-center prospective observation conducted lymphocyte subgroup analysis of blood samples and 16S rRNA gene amplicons sequencing and untargeted metabolomics analysis of fecal samples from 36 subjects with the persistent (≥3d) (n = 21) and non-persistent lymphopenia (<3d) (n = 15).

Results

The persistent lymphopenia showed higher the 28d mortality and 90d mortality, while significantly lower CD3⁺T/LY, CD3⁺T cells, CD3⁺CD4⁺T cells, CD3⁺CD8⁺T cells, Th1 cells, Th2 cells, CD45RA ⁺ Treg cells. The 16S rRNA results showed that Staphylococcus, Peptostreptococcus, Bulleidia, Leuconostoc were significant enriched in the persistent lymphopenia. The metabolomics analysis showed that α-Ketoisovaleric acid was increased and 7-DHCA, α-MCA, β-MCA, HCA, LCA-3S, CA, UCA and Citramalic acid were decreased in the persistent lymphopenia.

Conclusion

In the process of interaction between host receptors and gut microbiota in patients with persistent lymphopenia sepsis, with a significant reduction in gut microbiota diversity and bile acid metabolites. That can affect various inflammatory pathways of gut immune cells, causing immune dysfunction in the body, which may be one of the main causes of death.