β-glucan mitigates necrotizing enterocolitis-induced long-term cognitive impairment by remodeling gut microbiota and restoring tryptophan metabolite IAA-mediated gut–brain signaling
- 1Department of Neonatology, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, China
- 2Bishan Maternal and Child Health Care Hospital, Chongqing, China
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.
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BibTeX
@article{zhang2026βglucan,
title = {{β-glucan mitigates necrotizing enterocolitis-induced long-term cognitive impairment by remodeling gut microbiota and restoring tryptophan metabolite IAA-mediated gut–brain signaling}},
author = {Xingdao Zhang and Haiyan Cao and Yuni Zhang and Yuan Shi},
journal = {Gut Microbes},
year = {2026},
month = nov,
doi = {10.1080/19490976.2026.2756699},
url = {https://doi.org/10.1080/19490976.2026.2756699},
note = {CC BY},
}
RIS
TY - JOUR
TI - β-glucan mitigates necrotizing enterocolitis-induced long-term cognitive impairment by remodeling gut microbiota and restoring tryptophan metabolite IAA-mediated gut–brain signaling
AU - Xingdao Zhang
AU - Haiyan Cao
AU - Yuni Zhang
AU - Yuan Shi
PY - 2026
DA - 2026/11/07
JO - Gut Microbes
DO - 10.1080/19490976.2026.2756699
UR - https://doi.org/10.1080/19490976.2026.2756699
AB - 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.
SN - 1949-0984
SN - 1949-0976
ER -