Frontiers in molecular neuroscienceOct 27, 2026

How short-chain fatty acids may help newborn brain injury by improving cell energy and reducing stress

Gut-Brain Axis Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Oct 28, 2026

Abstract

Neonatal hypoxic-ischemic encephalopathy (HIE) is a leading cause of neonatal mortality and neurodevelopmental impairments.

HIE results from perinatal asphyxia and is associated with severe neurological disorders.
Common long-term effects of HIE include cerebral palsy, epilepsy, and cognitive deficits.
Therapeutic hypothermia is currently an effective intervention, but it has limitations, including a narrow treatment window.
Short-chain fatty acids (SCFAs) may offer neuroprotective effects through the gut-brain axis.
SCFAs could potentially modulate mitochondrial dysfunction and endoplasmic reticulum stress in the context of HIE.

Simplified

Neonatal hypoxic-ischemic encephalopathy (HIE) is a common severe neurological disorder following perinatal asphyxia and a leading cause of neonatal mortality and long-term neurodevelopmental impairments, including cerebral palsy, epilepsy, and cognitive and behavioral deficits. It remains one of the primary causes of death and disability in newborns, imposing a substantial burden on families and society. Although therapeutic hypothermia is currently recognized as an effective intervention, its narrow treatment window, limited patient eligibility, and the persistence of significant sequelae in some affected infants underscore the urgent need for adjunctive therapeutic strategies targeting novel mechanisms. In recent years, short-chain fatty acids (SCFAs), which are metabolites of the gut microbiota, have garnered considerable attention due to their neuroprotective effects via the gut-brain axis. This article systematically reviews the potential mechanisms and therapeutic prospects of SCFAs in neonatal HIE, focusing on their modulation of mitochondrial dysfunction and endoplasmic reticulum stress (ERS).

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How short-chain fatty acids may help newborn brain injury by improving cell energy and reducing stress

Abstract

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