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 germfree 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.

WITHDRAWN: Enterococcus Faecium is a Risk Factor for The Outbreak of Anxiety and Depression in Patients With Inflammatory Bowel Disease

“…Kim et al reported that Escherichia coli treatment increased the NF-κB + /Iba1 + and LPS + /Iba1 + cell populations in the hippocampus and LPS levels in the blood and feces and decreased the BDNF + /NeuN + cell population and tight-junction protein expression, resulting in the occurrence of depression [29]. Lee et al also reported that oral gavage of Escherichia coli and LPS caused colitis and neuroin ammation in mice through the suppression of tight-junction proteins [38]. Koo et al showed that the inhibition of IL-1β expression by pre-treatment with an IL-1R antagonist mitigated depression [39].…”

A Probiotic Lactobacillus gasseri Alleviates Escherichia coli-Induced Cognitive Impairment and Depression in Mice by Regulating IL-1β Expression and Gut Microbiota

“…Third, to understand the effect of NK109 on the vagus nerve-mediated gut–brain signaling, we prepared the SPF mice with celiac vagotomy, as reported previously [ 20 ]. The mice were separated into vehicle-treated group in sham mice (CoV), Escherichia coli K1-treated (vEcV) and NK109-treated groups in K1-treated mice with vagotomy (vENK) vehicle-treated group in sham mice (CoV), Escherichia coli K1-treated (vEcV) and NK109-treated groups in K1-treated mice with vagotomy (vENK).…”

“…For the immunohistochemistry analysis, the mice were perfused transcardially with 4% paraformaldehyde. Hippocampi and colons were removed, post-fixed with 4% paraformaldehyde, immersed in 30% sucrose solution, frozen, and sectioned using a cryostat, as reported previously [ 20 ]. The sections were incubated with antibodies for NF-κB (1:100), CD11c (1:200), Iba1 (1:200), BDNF (1:200), IL-IR (1:200), and/or NeuN (1:200) and incubated with the Alexa Fluor 488 (1:200)- or Alexa Fluor 594 (1:200)-conjugated secondary antibody [ 6 ].…”

A Budding Relationship: Bacterial Extracellular Vesicles in the Microbiota-Gut-Brain Axis

“…Other investigators have also demonstrated that whole gut bacteria stimulate the vagus nerve indirectly via released metabolites interacting with the enteric nervous system [ 12 , 118 ]. That bacterial MV could utilize the vagus nerve to mediate gut–brain communication was suggested by a recent study by Lee et al [ 119 ]. The investigators performed a fecal transplant from both older humans and aged mice into young mice and examined changes in dementia-related behavior and physiology.…”

“…The investigators performed a fecal transplant from both older humans and aged mice into young mice and examined changes in dementia-related behavior and physiology. Lee et al [ 119 ] demonstrated that MV derived from Paenalcaligenes hominis caused cognitive deficits in the brain as well as increasing the number of activated microglia in the hippocampus [ 119 ]. Cognitive deficits significantly reduced, and the hippocampal cell populations normalized in vagotomized animals suggesting that MV interaction with the vagus nerve is at least partially responsible for the MV induced changes to the brain [ 119 ].…”