The extracellular vesicle of gut microbial Paenalcaligenes hominis is a risk factor for vagus nerve-mediated cognitive impairment.

ABSTRACT

BACKGROUND: In a pilot study, we found that feces transplantation from elderly individuals to mice significantly caused cognitive impairment. Paenalcaligenes hominis and Escherichia coli are increasingly detected in the feces of elderly adults and aged mice. Therefore, we isolated Paenalcaligenes hominis and Escherichia coli from the feces of elderly individuals and aged mice and examined their effects on the occurrence of age-related degenerative cognitive impairment and colonic inflammation in mice. RESULTS: The transplantation of feces collected from elderly people and aged mice caused significantly more severe cognitive impairment in transplanted young mice than those from young adults and mice. Oral gavage of Paenalcaligenes hominis caused strong cognitive impairment and colitis in specific pathogen-free (SPF) and germ-free mice. Escherichia coli also induced cognitive impairment and colitis in SPF mice. Oral gavage of Paenalcaligenes hominis, its extracellular vesicles (EVs), and/or lipopolysaccharide caused cognitive impairment and colitis in mice. However, celiac vagotomy significantly inhibited the occurrence of cognitive impairment, but not colitis, in mice exposed to Paenalcaligenes hominis or its EVs, whereas its lipopolysaccharide or Escherichia coli had no such effects. Vagotomy also inhibited the infiltration of EVs into the hippocampus. CONCLUSIONS: Paenalcaligenes hominis, particularly its EVs, can cause cognitive function-impaired disorders, such as Alzheimer's disease, and its EVs may penetrate the brain through the blood as well as the vagus nerve. Video Abstract.