From gut to brain: effects of fecal microbiota transplants from humans to rats on hippocampal gene regulation - a study on anorexia nervosa

Abstract Fecal microbiota transplantation (FMT) has emerged as a novel approach for understanding anorexia nervosa (AN), a complex eating disorder characterized by severe underweight, fear of weight gain and distorted body image. Patients with AN show alterations in the gut microbiome, brain structure, and inflammatory processes, indicating the importance of the microbiome‒gut‒brain axis in AN pathology. This study aimed to investigate whether FMT from patients with AN into antibiotic-treated rats could transfer a phenotype associated with the disease inducing AN-like symptoms and hippocampal alterations. Female Wistar rats received antibiotics followed by FMT from healthy controls, patients with AN, or water. Gut microbiota effects were assessed through 16S rRNA gene sequencing, alongside post-mortem analyses of glial cells, neurogenesis markers, and inflammatory markers. The results revealed dysregulated microbial diversity after antibiotic treatment, which was partially restored after FMT. Successful transfer of human bacterial species was observed, but AN-like symptoms and changes in glial/neuronal counts were not detected. Notably, a decrease in hippocampal Bdnf expression was detected in the antibiotic control group, which was reversed by healthy control stool transplantation but not in the AN-transplanted group. Similar patterns were observed for neuroinflammation and Mki67, a marker of cell neogenesis. These findings suggest potential links between microbial changes, neuroinflammation and neuroplasticity in the hippocampus with the potential to correct deficits with FMT. Future studies should extend these findings by exploring the combination of FMT and starvation phases to better understand the roles of specific microbial populations in neuroinflammatory processes and, ultimately, clinical outcomes in AN.