Gupta, A.; Yadav, N.; Nanda, R.

Time-restricted feeding (TRF) in human and animal model systems has been reported to positively impact metabolic health by improving glucose homeostasis and reducing adiposity. However, limited studies have demonstrated its impact on infection conditions like Mycobacterium tuberculosis. We subjected 6-8 weeks old male C57BL/6 mice to 8 hr (9 pm to 5 am, lights on/off: 8 am/pm) of TRF for 30 days, and then aerosol infected them with a low dose (100-400 cfu) of Mycobacterium tuberculosis (Mtb) H37Rv. We measured tissue mycobacterial burden and CD4+ T-cell distribution at 21 days post-infection (dpi). The TRF mice showed minimal weight gain with better glucose tolerance. In addition, the serum and lung tissue metabolome of TRF and ad-libitum control mice were monitored by using mass spectrometry. The serum and liver metabolome of TRF mice demonstrated perturbation in pathways associated with amino acids and fatty acids. Mtb infection in TRF mice impacted the tyrosine and arachidonic acid metabolism, which may benefit the host. At 21 dpi, the Mtb-infected TRF mice showed tissue (lung, spleen and liver) Mtb load similar to the controls but a significant decrease in the number of CD3+ T cells in the bone marrow and CD3+CD4+ T cells in the bone marrow and lungs. TRF helps in improving metabolic health, but its effects are lost if it is discontinued.