SummaryBackground The ways in which Mycobacterium tuberculosis (Mtb) infection affects host metabolism and its implications for disease pathogenesis remain poorly understood. Understanding how Mtb shapes the metabolic state of the host could lead to nutritional and host-directed therapies to improve TB outcomes. Methods We performed high-resolution metabolic and lipid profiling on male rhesus macaques infected with Mtb (n = 17). Serial plasma samples were analysed beginning at the time of infection and up to 15–16 weeks post infection. Observed host metabolic changes were examined in a cohort of Mtb-infected (TBI, positive QuantiFERON Gold QFT; n=92) and Mtb-uninfected (TBU, negative QFT; n=102) participants as well as those with pulmonary TB (PTB; n=68). Findings Using principal component analysis, we found the greatest metabolic changes in NHPs occurred 15–16 weeks after experimental infection. Metabolic changes were characterised by declines in saturated, monounsaturated, and polyunsaturated long chain fatty acids (LCFAs) including linoleic acid, linolenic acid, docosahexaenoic acid, and palmitoleic acid. Humans with TBI also experienced significant declines in plasma concentrations of nearly all species of LCFAs 6 months after Mtb exposure. In participants with PTB, LCFAs were further depleted relative to those with TBI but gradually normalised six months post-TB treatment. Interpretation Our study shows the host metabolic response to infection with Mtb is characterised by the systemic depletion of host lipids, which is exacerbated in persons with PTB. Interventions that supplement host lipids should be tested to determine their impact on TB outcomes. Funding This work was supported by grants from the U.S. National Institute of Allergy and Infectious Diseases (NIAID) R01 AI182244, R21 AI178324, K23 AI144040, P30 AI168386, P30 AI050409, K24 AI114444, U19 AI111211; and the National Center for Advancing Translational Sciences UL1 TR002378, Bethesda, MD, USA. The study sponsors had no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication.
Collins et al. (Fri,) studied this question.