Peripheral blood microbiome signature and Mycobacterium tuberculosis-derived rsRNA as diagnostic biomarkers for tuberculosis in humanOriginal paper
Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease, four years before the first published case study.
Read MoreWhat was studied?
This study characterized the peripheral blood microbiome of tuberculosis (TB) patients using RNA sequencing, aiming to find non-sputum biomarkers for TB diagnosis. The researchers focused on identifying Mycobacterium tuberculosis (Mtb) genome-derived small RNA molecules, specifically rRNA-derived small RNAs (rsRNAs), circulating in blood. They analyzed blood microbiome RNA signals across bacteria, fungi, archaea, and viruses, and then tested candidate Mtb rsRNAs as potential diagnostic markers. Small RNA sequencing was also performed on plasma exosomes to further probe these RNA signatures.
Who was studied?
The initial analysis used RNA sequencing data from the blood of TB patients and healthy controls retrieved from the NCBI-SRA public database. Small RNA sequencing was additionally performed on plasma exosomes from TB patients and healthy controls. Candidate Mtb rsRNA levels were then validated by RT-qPCR in a separate cohort of 73 TB patients and 62 healthy controls. Together these groups combined public sequencing data with a defined clinical validation cohort.
What were the most important findings?
The blood microbiome of TB patients contained RNA signals from bacteria, fungi, archaea, and viruses, with bacteria making up more than 97% of the total signal. TB patients showed reduced blood microbial diversity and reduced abundance of six Mycobacterium-associated bacterial genera, including Mycobacterium and Priestia. Mtb-derived rsRNAs were detectable in blood and plasma exosomes, distinguishing TB patients from healthy controls in the validation cohort of 73 patients and 62 controls.
What are the greatest implications of this study?
These findings suggest that blood microbiome signatures and circulating Mtb-derived rsRNAs could serve as non-sputum, blood-based diagnostic biomarkers for tuberculosis. This approach could help address the ongoing challenge of early TB diagnosis, particularly for patients who cannot easily produce sputum samples. The reduced microbial diversity and altered Mycobacterium-associated genera also point to broader shifts in the blood microbiome accompanying active TB infection. Validating these markers in a defined patient cohort supports their potential clinical translation as a diagnostic test.