Lung Mycobacterium tuberculosis infection perturbs metabolic pathways in non-pulmonary tissues

Mycobacterium tuberculosis (Mtb), through aerosol, reaches the lungs to cause pulmonary tuberculosis (TB); however, it may also affect the metabolism of other tissues in age-specific ways. In this study, female C57BL/6 mice (2 and 5 months old; M) were infected with a low aerosol dose (100-200 cfu) of Mtb H37Rv to monitor tissue mycobacterial load and multi-tissue metabolite profiling using gas chromatography and mass spectrometry (GC-MS). 5M C57BL/6 mice showed separate tissue metabolic phenotype with significantly higher lung aspartic acid, fecal oxalic acid and tryptophan levels with lower liver lysine and aspartic acid and fecal phenylalanine levels (log2FC: 5M/2M> {+/-}1.0, p<0.1) compared to 2M young controls. Upon Mtb infection, the lung mycobacterial load of 2M and 5M mice were similar till 6 weeks post-infection. However, significantly higher lung phosphoric acid, malonic acid and lower mannose levels (log2FC: Mtb infected/healthy> {+/-}1.0, p<0.1) were observed in Mtb-infected 5M C57BL/6 mice. Meanwhile, Mtb-infected 2M mice showed higher liver xylose and lower lysine levels. The thigh muscles of Mtb-infected 2M and 5M mice showed increased malic acid and oxalic acid and decreased glycine, serine, and glycerol levels. Fecal aspartic acid level was higher in Mtb-infected 5M mice, while a decreased abundance of fecal lysine was observed in Mtb-infected 2M mice. Overall, this study demonstrates a deregulated tissue-specific amino acid metabolism in Mtb-infected mice groups of different age groups, which might be targeted for managing TB infection-related adverse effects.