Pre-exposure to time-restricted feeding reduces tissue CD4+ T cells with a limited effect on Mycobacterium tuberculosis clearance at early time point

Time-restricted feeding (TRF) in human and animal models positively impacts metabolic health by improving glucose homeostasis and reducing adiposity. However, limited studies have investigated the impact of TRF on the host immune response and in infection. In this study, C57BL/6 mice (6–8 weeks old, male) were subjected to 8 hours of dark-phase TRF for 30 days, and aerosol infected with a low dose (100-400 colony-forming units) of Mycobacterium tuberculosis (Mtb) H37Rv. The body weight gain, tissue metabolite, proteome and immune cell components of these study groups were profiled. At 15 days post TRF, mice showed marginal weight loss with better glucose tolerance. The serum and liver metabolome of TRF mice demonstrated perturbed amino acids and fatty acids metabolic pathways. TRF mice liver proteome profiling indicated increased fatty acid oxidation. The Mtb-infected TRF and control mice had similar tissue (lung, spleen and liver) Mtb burden at 21 days post infection. The bone marrow of Mtb-infected TRF mice had significantly lower CD3+ T cells and CD4+ T cells were low both in the bone marrow and lungs. This study reports that mice undergoing TRF had an improved metabolic phenotype and discontinuing limits its positive impact on handling Mtb at early time points.