<b>From nose to brain: Olfaction loss induces Alzheimer's disease (AD) syndrome via the microbiota-gut-brain axis</b>

<b>Background: </b>Olfactory dysfunction is frequently observed in Alzheimer's disease (AD); however, very little is known about whether olfactory disorders trigger cognitive impairment or just act as early biomarkers of AD syndrome. In this study, we induced olfactory loss in C57BL/6 mice and investigated whether and how olfactory loss induces AD-like behaviors. <b>Results:</b> Our results demonstrate that olfactory loss not only causes a significant decrease in food intake and body weight and an increase in O₂ consumption but also induces AD-like cognitive impairment and anxiety-like behaviors. Moreover, the alteration in the gut microbiota induced by olfactory loss is followed by changes in cecal short fatty acids and serum neurotransmitters. The significant changes in AD-related proteins and pathways in the hippocampus show further evidence that the gut microbiota and cognition are linked via metabolic and signaling pathways in response to olfaction loss. Fecal microbial transplantation provides further support for the mechanisms by which olfactory loss triggers AD-like syndrome via the microbiota–gut–brain axis. <b>Conclusions: </b>Our study is expected to provide some of the first evidence for olfactory dysfunction in triggering AD syndrome, providing a foundation for future AD research on olfactory and cognitive function through the microbiota–gut–brain axis.