To investigate and explore intestinal microecology, brain functional activity, and interregional connectivity features in rats with copper-overloaded diet. Rat models of copper-overloaded were developed through copper sulfate-loaded diet. The successfully modeled rats were randomly divided into the model group (MG) and D-penicillamine group (DPA), while a naive control group (CG) consisting of non-modeled rats was established. Fecal samples of rats in different groups were randomly collected after 7, 14, and 28 days of treatment, respectively, and analyzed by 16S rRNA sequencing. Rats were scanned by resting-state functional magnetic resonance imaging (rs-fMRI). Hematoxylin and eosin staining was employed for histopathological examination of livers. (1) 16S rRNA sequencing: Compared with the CG group, the MG and DPA groups exhibited significantly increased relative abundances of Actinobacteriota and Corynebacterium and significantly decreased relative abundances of Lactobacillus and Limosilactobacillus ( P < 0.05). (2) rs-fMRI scanning: levels of fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) were significantly increased in the MG group and significantly decreased in the DPA group compared with the CG group. Compared with the CG group, the MG group exhibited impaired functional connectivity (FC) between the seed point and multiple brain regions, while DPA treatment restored FC in regions with disrupted connectivity (e.g., the hypothalamic preoptic area, hypothalamic nodular area, hypothalamic supraoptic area, midbrain dorsal tegmentum, and tegmentum of pons). Rats with copper-overloaded diet were exposed to gut microbiota disorder, accompanied by abnormal FC and interregional connectivity. Copper excretion therapy alleviated craniocerebral impairment in these rats. The hypothalamus-brainstem-gut-brain axis may serve as the core central nervous system mechanism underlying the regulation of the gut microbiota in copper-overloaded rats.
Tao et al. (Mon,) studied this question.