The epigenetic legacy of ICU feeding and its consequences

Abstract

Purpose of reviewMany critically ill patients face physical, mental or neurocognitive impairments up to years later, the etiology remaining largely unexplained. Aberrant epigenetic changes have been linked to abnormal development and diseases resulting from adverse environmental exposures like major stress or inadequate nutrition. Theoretically, severe stress and artificial nutritional management of critical illness thus could induce epigenetic changes explaining long-term problems. We review supporting evidence.Recent findingsEpigenetic abnormalities are found in various critical illness types, affecting DNA-methylation, histone-modification and noncoding RNAs. They at least partly arise de novo after ICU-admission. Many affect genes with functions relevant for and several associate with long-term impairments. As such, de novo DNA-methylation changes in critically ill children statistically explained part of their disturbed long-term physical/neurocognitive development. These methylation changes were in part evoked by early-parenteral-nutrition (early-PN) and statistically explained harm by early-PN on long-term neurocognitive development. Finally, long-term epigenetic abnormalities beyond hospital-discharge have been identified, affecting pathways highly relevant for long-term outcomes.SummaryEpigenetic abnormalities induced by critical illness or its nutritional management provide a plausible molecular basis for their adverse effects on long-term outcomes. Identifying treatments to further attenuate these abnormalities opens perspectives to reduce the debilitating legacy of critical illness.

Nutrition and autophagy deficiency in critical illness

“…The long-term impact of nutritional management in ICU on autophagy in relation to the long-term adverse legacy after critical illness [104–110,131 ▪ ,132] remains unclear. Epigenetic abnormalities induced by critical illness or its nutritional management provide a plausible molecular basis for their adverse effects on long-term outcomes [133–136,137 ▪ ]. Autophagy is prone to epigenetic regulation, and abnormal DNA methylation of genes involved in autophagy was observed in the muscles of critically ill patients versus matched controls [137 ▪ ].…”

Abnormal DNA methylation within genes of the steroidogenesis pathway two years after paediatric critical illness and association with stunted growth in height further in time

“…Children who have been critically ill face substantial risk of long-term health problems and impairments in physical, neurocognitive and emotional/behavioural development, up to years after hospital discharge [ 1 – 8 ]. The mechanisms explaining adverse long-term outcomes after critical illness remain largely unclear, but epigenetic abnormalities induced by critical illness or associated treatments have been suggested as a plausible molecular basis [ 9 ]. Interestingly, estimation of “epigenetic” or biological age, with an epigenetic clock developed for children on buccal mucosa DNA [ 10 ], revealed an age deceleration in former critically ill children 2 years after PICU admission, as compared with normally developing healthy children, with stunted growth in height 2 years further in time as a physical correlate [ 11 ].…”

The power of the gut in critical care

“…A personalized nutrition plan can prevent the risks of over- or underfeeding and help to preserve muscle mass. Puthucheary et al [3] and Van den Berghe et al [4] focus on the effect of nutrition in the post intensive care period. A loss of muscle mass occurs early and rapidly during an episode of critical illness [5].…”

“…Van den Berghe et al [4] provide a fascinating overview on the epigenetic legacy of ICU feeding and its consequences. Epigenetic changes, including changes in DNA methylation, histone modification, and noncoding RNAs, have been linked to long-term physical, mental, or neurocognitive impairments in critically ill patients.…”

“…What are the long term consequences of intensive care unit (ICU) feeding? Now, Van Zanten et al [2], Puthucheary et al [3] and Van den Berghe et al [4] address these pressing questions.…”