Fecal microbiota transplantation ameliorates high‐fat diet‐induced memory impairment in mice

Gut dysbiosis is linked to metabolic and neurodegenerative diseases and comprises a plausible link between high‐fat diet (HFD) and brain dysfunction. Here we show that gut microbiota modulation by either antibiotic treatment for 5 weeks or a brief 3‐day fecal microbiota transplantation (FMT) regimen from low‐fat (control) diet‐fed mice decreased weight gain, adipose tissue hypertrophy, and glucose intolerance induced by HFD in C57BL/6 male mice. Notably, gut microbiota modulation by FMT completely reversed impaired recognition memory induced by HFD, whereas modulation by antibiotics had less pronounced effect. Improvement in recognition memory by FMT was accompanied by decreased HFD‐induced astrogliosis in the hippocampal cornu ammonis region. Gut microbiome composition analysis indicated that HFD diminished microbiota diversity compared to control diet, whereas FMT partially restored the phyla diversity. Our findings reinforce the role of the gut microbiota on HFD‐induced cognitive impairment and suggest that modulating the gut microbiota may be an effective strategy to prevent metabolic and cognitive dysfunction associated with unfavorable dietary patterns. This study investigated the impact of gut microbiota modulation on memory impairment and metabolic dysfunction induced by high‐fat diet (HFD) feeding. We found that antibiotic treatment and fecal microbiota transplantation (FMT) from low‐fat diet‐fed donor mice ameliorated metabolic outcomes induced by HFD. Notably, FMT, but not antibiotic treatment, reversed impaired recognition memory induced by HFD. The latter finding was accompanied by diminished HFD‐induced astrogliosis in the hippocampal cornu ammonis region and restored fecal microbiota diversity. The findings indicate that targeting gut dysbiosis may be a potential therapeutic strategy for cognitive dysfunction induced by excessive dietary fat (image created with Biorender.com®).