Background Previous brain studies of growth hormone deficiency (GHD) often used single-mode neuroimaging, missing the complexity captured by multimodal data. Growth hormone affects gut microbiota and metabolism in GHD. However, from a gut-brain axis perspective, the relationship between abnormal GHD brain development and microbiota alterations remains unclear. The ultimate goal is to uncover the manifestations underlying gut-brain axis (GBA) abnormalities in GHD and idiopathic short stature (ISS). Methods Participants included 23 GHD and 25 ISS children. The fusion independent component analysis was applied to integrat multimodal brain datas (high resolution structural, diffusion tensor, and resting state functional MRI) covering regional homogeneity (ReHo), amplitude of low frequency fluctuations (ALFF), and White matter fractional anisotropy (FA). Gut microbiome diversity and metabolites were analyzed using 16S sequencing and proton nuclear magnetic resonance (1H-NMR). Associations between multimodal neuroimaging and cognition were assessed using moderation analysis. Results Six components (ReHo, ALFF, and FA) differed significantly between GHD and ISS patients, with three functional components linked to processing speed. GHD individuals showed higher levels of acetate in microbiota metabolism. Higher alpha diversity in GHD strengthened connections between ReHo-IC1, ReHo-IC5, ALFF-IC1, and processing speed, while increasing Agathobacter levels in ISS weakened the link between ALFF-IC1 and speech comprehension. Conclusions Our findings uncover differing brain structure and functional fusion in GHD, alongside microbiota metabolism of short-chain fatty acids. Additionally, microbiome influences connections between neuroimaging and cognition, offering insight into diverse gut-brain axis patterns in GHD and ISS, enhancing our understanding of the disease's pathophysiology and interventions.
S. Karger AG, Basel.