Gut microbiota composition can reflect immune responses of latent tuberculosis infection in patients with poorly controlled diabetes

Abstract

Background Diabetes mellitus (DM) is a major risk factor for tuberculosis (TB). Evidence has linked the DM-related dysbiosis of gut microbiota to modifiable host immunity to Mycobacterium tuberculosis infection. However, the crosslinks between gut microbiota composition and immunological effects on the development of latent TB infection (LTBI) in DM patients remain uncertain. Methods We prospectively obtained stool, blood samples, and medical records from 130 patients with poorly-controlled DM (pDM), defined as ever having an HbA1c > 9.0% within previous 1 year. Among them, 43 had LTBI, as determined by QuantiFERON-TB Gold in-Tube assay. The differences in the taxonomic diversity of gut microbiota between LTBI and non-LTBI groups were investigated using 16S ribosomal RNA sequencing, and a predictive algorithm was established using a random forest model. Serum cytokine levels were measured to determine their correlations with gut microbiota. Results Compared with non-LTBI group, the microbiota in LTBI group displayed a similar alpha-diversity but different beta-diversity, featuring decrease of Prevotella_9, Streptococcus, and Actinomyces and increase of Bacteroides, Alistipes, and Blautia at the genus level. The accuracy was 0.872 for the LTBI prediction model using the aforementioned 6 microbiome-based biomarkers. Compared with the non-LTBI group, the LTBI group had a significantly lower serum levels of IL-17F (p = 0.025) and TNF-α (p = 0.038), which were correlated with the abundance of the aforementioned 6 taxa. Conclusions The study results suggest that gut microbiome composition maybe associated with host immunity relevant to TB status, and gut microbial signature might be helpful for the diagnosis of LTBI.

Discovery of urinary biosignatures for tuberculosis and nontuberculous mycobacteria classification using metabolomics and machine learning

“…Furthermore, indole-3-carboxyaldehyde, a derivative of tryptophan derived from the gut microbiota, was found to suppress IL-6 cytokine production of murine macrophages in response to stimulation by Mtb 61 . Previous reports have also correlated the gut microbiome with host immune responses to Mtb infection 62 and NTM infection 63 . The alteration of indole-3-carboxyaldehyde in our study may be partially explained by the role of tryptophan metabolism mediated by gut microbiome in the immune responses to NTM infection and TB.…”

Latent tuberculosis infection is associated with an enrichment of short chain fatty acid producing bacteria in the stool of women living with HIV

“…However, it is comparatively understudied in latent TB. One study among individuals with poorly-controlled diabetes, showed LTBI-positives people to be Bacteroides-, Alistipes-, and Blautiaenriched compared to LTBI-negatives 7 .…”

Latent Tuberculosis Infection Is Associated with an Enrichment of Short-Chain Fatty Acid-Producing Bacteria in the Stool of Women Living with HIV

“…However, it is comparatively understudied in latent TB. One study among individuals with poorly controlled diabetes showed LTBI-positive people to be Bacteroides -, Alistipes -, and Blautia -enriched compared to LTBI-negative people [ 9 ]. During LTBI infection, comparisons of TB cases, HIV-negative LTBI-positive individuals, and LTBI-negative and active TB gut microbiomes showed trends of changes in Bacteroides and Firmicutes; however, no significant difference was observed in the composition of the stool microbiota [ 10 ].…”