Work

β-glucan mitigates necrotizing enterocolitis-induced long-term cognitive impairment by remodeling gut microbiota and restoring tryptophan metabolite IAA-mediated gut–brain signaling

Year: 2026

Type: article

Abstract: Necrotizing enterocolitis (NEC) is a life-threatening gastrointestinal disorder prevalent in preterm infants, and most NEC survivors suffer from persistent cognitive deficits and neurodevelopmental disorders, with no targeted therapeutic approaches available to date. β-glucan has been documented to regulate gut microbiota, suppress inflammation, and exert neuroprotective effects, yet its efficacy and molecular mechanisms against NEC-associated cognitive dysfunction remain unclear. In this study, we established a mouse NEC model with β-glucan intervention to explore its gut–brain axis protective effects. Behavioral assessments verified that β-glucan significantly rescued NEC-induced cognitive impairments, with comparable therapeutic effects between low and high doses. Multi-omics analyses demonstrated that β-glucan effectively reversed NEC-triggered gut microbiota dysbiosis and restored disrupted tryptophan metabolism, notably elevating the level of indole-3-acetic acid (IAA). Fecal microbiota transplantation and exogenous IAA supplementation recapitulated the neuroprotective phenotypes of β-glucan, which inhibited excessive hippocampal microglial activation and neuroinflammation, and repaired impaired synaptic ultrastructure and plasticity. Further mechanistic validation confirmed that IAA mediated neuroprotection via activating the AHR/MAP2K3/p38 signaling cascade. Collectively, β-glucan alleviates NEC-related cognitive injury through modulating the gut microbiota–tryptophan metabolism–IAA axis and subsequent AHR/MAP2K3/p38 signaling activation. This study elucidates a novel gut‒brain axis regulatory mechanism of β-glucan, providing reliable preclinical evidence for the clinical prevention and treatment of long-term neurodevelopmental complications in NEC survivors.

Source: Gut Microbes

DOI: 10.1080/19490976.2026.2756699

Authors: Xingdao Zhang, Haiyan Cao, Yuni Zhang, Yuan Shi

Institution: Children's Hospital of Chongqing Medical University

Language: English

Topic: Infant Nutrition and Health

Subfield: Nutrition and Dietetics

Field: Nursing

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,060