The following is a summary of “Circulating N-formylmethionine and metabolic shift in critical illness: a multicohort metabolomics study,” published in the October 2022 issue of Critical Care by Sigurdsson, et al.

Stress on a cell speeds up the breakdown of its mitochondria, which then release dangerous molecular patterns that are broken down into N-formylmethionine. Researchers thought that the response to N-formylmethionine in very sick adults would be linked to an increase in metabolites related to metabolomic shifts and an increase in 28-day mortality. They  did metabolomics analyses on plasma from the Correction of Vitamin D Deficiency in Critically Ill Patients Trial (VITdAL-ICU) cohort of 428 people and the Registry of Critical Illness (RoCI) cohort of 90 people at Brigham and Women’s Hospital. In the VITdAL-ICU cohort looked at 983 metabolites on admission to the ICU, on day 3, and on day 7. They looked at 411 metabolites when the RoCI cohort was admitted to the ICU.

Adjusted logistic regression was used to figure out the link between N-formylmethionine and death. With false discovery rate correction, linear regression, linear mixed-effects, and Gaussian graphical models were used to examine the relationship between individual metabolites and the amount of N-formylmethionine. In the VITdAL-ICU (OR, 2.4; 95% CI, 1.5–4.0; P=0.001) and RoCI (OR, 5.1; 95% CI, 1.4–18.7; P=0.015) cohorts, patients who were in the top quartile of N-formylmethionine abundance when they were admitted to the ICU had a much higher chance of dying within 28 days. Adjusted linear regression shows that 55 metabolites have significant differences between the VITdAL-ICU and RoCI cohorts when the amount of N-formylmethionine at admission to the ICU goes up.

With more N-formylmethionine, metabolites from the short-chain acylcarnitine pathway, the branched-chain amino acid pathway, the kynurenine pathway, and the pentose phosphate pathway all went up in both groups. The results show that circulating N-formylmethionine promotes a metabolic shift that increases mortality. This metabolic shift includes incomplete mitochondrial fatty acid oxidation, increased branched-chain amino acid metabolism, and activation of the pentose phosphate pathway.