The alternation of gut microbiome composition can predict latent tuberculosis infection status in poorly-controlled diabetic patients: A prospective case-controll study

<b>Background:</b> Poorly controlled diabetic mellitus (pDM) has been regarded as a major risk factor for tuberculosis (TB) disease. Accumulating evidence has linked DM related dysbiosis of gut microbiome to modifiable host immunity, and thus facilitates infection with&nbsp;Mycobacterium tuberculosis. However, the crosslinks between gut microbiota composition and immunological impact on the development of latent TB infection (LTBI) in pDM patients remains uncertain. <b>Methods:</b> We prospectively obtained stool, blood and medical records from 130 pDM patients (43 LTBI and 87 nonLTBI), whose HbA1c &gt;9.0% within previous 1 year. Interferon-gamma release assay was used for LTBI screening. The differences in gut microbial taxonomy diversity between groups were investigated by using 16S ribosomal RNA sequencing, and a classification model was established by illustrating area under curve (AUC). Sera cytokine was quantified by ELISA. <b>Results:</b> Compared with patients with DM-nonLTBI, the microbiota from DM-LTBI patients displayed similar alpha-diversity but distinguished with respect to beta-diversity, and featured by decrease of Prevotella, Actinomyces, and Streptococcus, and increase of Bacteroides, Alistipes and Blautia. The AUC was 0.917 of a predictive model with 9 microbiome-biomarkers to distinguish DM-nonLTBI and DM-LTBI cohorts. DM-LTBI groups had significantly lower serum level of IL-17F and TNF-α than DM-nonLTBI groups, which was correlated to aforementioned taxa. <b>Conclusions:</b> The alternation of gut microbiome composition may modulate host immunity potentially relevant to TB susceptibility in pDM patient to be&nbsp;a potential diagnostic biomarker.