Time-restricted feeding prior to Mycobacterium tuberculosis infection reduces tissue CD4+ T cells with limited impact on bacterial clearance.

The effects of time-restricted feeding (TRF) on immune responses during bacterial infection are not well-studied. Here, we subjected mice (6-8 weeks, male) to 8 h of TRF for 30 days and then infected them with a low dose of Mycobacterium tuberculosis (Mtb) H37Rv. During the first 15 days, TRF improved glucose tolerance with marginal weight loss. However, global serum and liver metabolomics alongside liver proteomics indicated that TRF perturbed fatty acid biosynthesis and degradation, steroid hormone biosynthesis, and tyrosine metabolism. Together, these results indicate that TRF potentially affected the distribution and functionality of host immune cells. TRF mice had similar mycobacterial burdens in lungs and spleen at 21 days postinfection but had significantly lower CD3+ T cells in bone marrow and CD4+ T cells in both bone marrow and lungs. Ultimately, we show that TRF induced changes in amino acid and lipid metabolism persist during Mtb infection.