Diabetes mellitus and tuberculosis comorbidity induce unique microbial gut dysbiosis and associated metabolome
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Background
Diabetes and tuberculosis (DMTB) comorbid patients show atypical disease presentation and poor prognosis during treatment. In diabetes, the impaired immune system could partially be explained by the altered gut microbiota. Understanding gut microbiota and their association with the metabolite profiles in DMTB conditions may help design adjunct therapeutics.
Method
Nicotinamide (NA) and streptozotocin (STZ) induced diabetic C57BL/6 mice were aerosol infected with 100-120 CFU of Mycobacterium tuberculosis H37Rv . At different time points (2 days pre-infection and 3- and 8 weeks post infections; wpi), faecal samples were collected for microbiome and metabolome profiling using 16S rRNA sequencing and gas chromatography-time of flight-mass spectrometry (GC-TOF-MS), respectively.
Results
Diabetic mice showed gut dysbiosis, 16 bacterial genera were significantly altered between DMTB and TB at 3 wpi, which reduced to 11 at 8 wpi. Out of 93 identified faecal metabolites, a set of 11 and 10 deregulated (log 2 FC>±1.0, p<0.05) metabolites were observed in the DMTB compared to TB groups at 3 and 8 wpi, respectively. Correlation analysis of microbiome and metabolome profiles showed a negative correlation between valeric acid levels in DMTB with the abundances of Coriobacteriaceae, Granulicatella, Veillonella, Achromobacter, Erysipelatrichaceae, Atopobiaceae, Citrobacter, and Lactiplantibacillus . Stronger metabolite-microbiota correlations were observed in DMTB comorbid conditions compared to TB. Correlation analysis also revealed phylogenetic distance-dependent synchrony in amino acid metabolism in five clades of 3 or more bacterial genera.
Conclusion
The present study highlights that the comprehensive landscape of gut microbiome and metabolome of DMTB are significantly different from TB. Certain microbes and metabolic products could be useful as pre/probiotic concoctions for DMTB comorbid conditions for better recovery.
