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

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 upon bacterial 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, multi-tissue metabolome, and proteome changes and distribution of immune cells in these study groups were monitored. In the first 15 days of TRF, mice showed better glucose tolerance with marginal weight loss. The serum and liver metabolome of TRF mice demonstrated perturbed fatty acid biosynthesis and degradation, steroid hormone biosynthesis pathways and tyrosine metabolism. Liver proteome data of TRF mice indicated an increased fatty acid oxidation which might affect the host immune cell frequency and functionality. The Mtb-infected TRF and control mice had similar tissue (lung, spleen and liver) bacterial 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 8 hours of TRF had an improved metabolic phenotype, and discontinuing TRF limits its positive impact on handling Mtb infection at an early point.