Metatranscriptomic insights into the dengue patient blood microbiome: Enhanced microbial diversity and metabolic activity in severe patients.

Background: Dengue is the most re-emergent infection, with approximately 100 million new cases reported annually, yet no effective treatment or vaccine exists. Here, we aim to define the microbial community structure and their functional profiles in the dengue positive patients with varying disease severity. Methodology/Principal findings: Hospital admitted 112 dengue-positive patients blood samples were analyzed by dual RNA-sequencing to simultaneously identify the transcriptionally active microbes (TAMs), their expressed genes and associated pathways. Results highlight that patients with severe dengue exhibited increased microbial diversity and presence of opportunistic species (unique and core) which includes Bacillus cereus, Burkholderia pseudomallei, Streptococcus suis, and Serratia marcescens. The functional profile analysis revealed enriched metabolic pathways such as protein degradation, nucleotide biosynthesis, ion transport, cell shape integrity, and ATP formation in severe cases, indicating the high energy demands and adaptability of these microbes. Conclusion: Our metatranscriptomic approach provides a species-level characterization of blood microbiome composition and reveals a heightened diversity of TAMs in patients with severe dengue, underscoring the need for further research into the role of blood microbiota in disease progression. Comparing the microbial signatures across the severity classes early in the disease offers unique potential for convenient and early diagnosis of dengue infection. Author summary: Dengue poses a significant public health challenge in tropical and subtropical regions. The lack of a specific treatment or broadly effective vaccine highlights the critical need for novel approaches. In this study, we investigated the transcriptionally active microbial species (TAMs) in 112 dengue-positive patients from MAX Hospital in Delhi, India, to identify their correlations with disease severity. RNA-seq analysis revealed an increased abundance of opportunistic TAMs in severe dengue patients, with some species showing significant associations with platelet counts and total leukocyte count (TLC). Our findings underscore the underappreciated importance of the blood microbiome in dengue, particularly the heightened metabolic activity of these opportunistic species in severe cases. This study offers valuable insights for early infection diagnosis for dengue management. The species-level data identified here could pave the way for systematic exploration of microbial involvement in dengue virus (DENV) infections, potentially serving as an indicator for new adjuvant treatment strategies. [ABSTRACT FROM AUTHOR]