Patients with diabetes mellitus (DM) who also have latent tuberculosis infection (LTBI) have a markedly different gut microbiome compared with patients with DM who do not have LTBI, according to study findings published in Respiratory Research.
Diabetes is a major risk factor for TB infection, and evidence has linked the diabetes-related dysbiosis of gut microbiota to modifiable host immunity to Mycobacterium tuberculosis infection. However, little is known about the links between latent TB infection status, host immunity, and gut microbiota dybiosis in patients with diabetes. Investigators in Taiwan therefore conducted a prospective cohort study of individuals with poorly controlled diabetes to explore the relationships between gut microbiota composition, host immunity, and LTBI development.
The study enrolled 130 patients at least 45 years of age with poorly controlled diabetes (defined as having a maximum HbA1c [hemoglobin A1] level of more than 9.0%) during the year prior to study enrollment, which occurred between October 2019 and December 2020. Stool, blood samples, and medical records were obtained from all patients.
Among participants, 43 had LTBI, as determined by QuantiFERON-TB Gold in-Tube assay, and 87 did not have LTBI. The mean participant age was 67.1 years and mean body mass index was 26.6 kg/m2. Overall, 51% of the patients were male and 80.0% did not smoke. The mean maximum HbA1c level within 1 year was 10.7%.
The investigators used 16S ribosomal RNA sequencing to evaluate the differences in the taxonomic diversity of gut microbiota between the LTBI and non-LTBI groups. A predictive algorithm was established with the use of a random forest model. Additionally, serum cytokine levels were measured to determine their associations with gut microbiota.
Researchers found that compared with patients without LTBI, those with LTBI had microbiota with similar alpha-diversity but different beta-diversity, displaying a decrease in Prevotella_9, Streptococcus, and Actinomyces, as well as an increase in Bacteroides, Alistipes, and Blautia, at the genus level. Notably, the microbiota-based model used by investigators, which involved the 6 most differential genera in gut microbiota, exhibited favorable performance, with an accuracy of 0.872 in the prediction of LTBI status among individuals with poorly controlled diabetes.
This study provides a foundation for explorations relevant to gut microbiome-based diagnostic biomarkers and host-directed treatment strategies; such explorations could alleviate the TB-DM co-epidemic.
Additionally, compared with patients without LTBI, those with LTBI had significantly lower serum levels of interleukin-17F (P =.025) and tumor necrosis factor α (P =.038), which were correlated with the abundance of the aforementioned 6 taxa.
Limitations of the analysis include its cross-sectional design, which did not allow for determinations of causal mechanisms for the effect of microbiota alterations on host immunity during different stages of M tuberculosis infection. Further, the use of 16S RNA sequencing, rather than shotgun metagenomics, may interfere with the taxonomic and functional resolution of the microbiomes because of the inadequacy of the gene-related information obtained from the various strains.
The authors concluded, “This study provides a foundation for explorations relevant to gut microbiome-based diagnostic biomarkers and host-directed treatment strategies; such explorations could alleviate the TB-DM co-epidemic.” They added that “A new diagnostic platform incorporating various diagnostic modalities for LTBI is necessary to guide point-of-care management and the timing of treatment initiation.”