Chronic early life stress alters the neuroimmune profile and functioning of the developing zebrafish gut

• Published in: Brain, behavior, & immunity. Health Vol. 31; p. 100655
• Main Authors: Graves, Christina L., Norloff, Erik, Thompson, Darius, Kosyk, Oksana, Sang, Yingning, Chen, Angela, Zannas, Anthony S., Wallet, Shannon M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2023; Elsevier
• Subjects: Anxiety; Chronic stress; Early life stress; Full Length; Gut; Neuroimmune; Zebrafish; Zebrafish; Early life stress; Chronic stress; Anxiety; Neuroimmune; Gut
• ISSN: 2666-3546; 2666-3546
• DOI: 10.1016/j.bbih.2023.100655

Chronic early life stress (ELS) potently impacts the developing central nervous and immune systems and is associated with the onset of gastrointestinal disease in humans. Though the gut-brain axis is appreciated to be a major target of the stress response, the underlying mechanisms linking ELS to gut dysfunction later in life is incompletely understood. Zebrafish are a powerful model validated for stress research and have emerged as an important tool in delineating neuroimmune mechanisms in the developing gut. Here, we developed a novel model of ELS and utilized a comparative transcriptomics approach to assess how chronic ELS modulated expression of neuroimmune genes in the developing gut and brain. Zebrafish exposed to ELS throughout larval development exhibited anxiety-like behavior and altered expression of neuroimmune genes in a time- and tissue-dependent manner. Further, the altered gut neuroimmune profile, which included increased expression of genes associated with neuronal modulation, correlated with a reduction in enteric neuronal density and delayed gut transit. Together, these findings provide insights into the mechanisms linking ELS with gastrointestinal dysfunction and highlight the zebrafish model organism as a valuable tool in uncovering how “the body keeps the score.”