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Millicent Ekwudo
Pronouns
She/Her/Hers
Job Title
Research Technician
Academic Rank
Department
Neurology
Authors
Joanna A. Korecka, Millicent N. Ekwudo, Danielle S. Leserve, Christian Gauthier, Manel Boussouf, Madelynn O’Brien, Kusha Chopra, Howard L. Weiner, Vikram Khurana, Laura M. Cox
Principal Investigator
Laura M. Cox
Research Category: Neurosciences
Tags
The gut microbiota and their metabolites modulate the neuroimmune axis in neurodegenerative diseases such as Parkinson’s disease (PD). Variable disease penetrance can occur in individuals with genetic risk factors, which we hypothesize may be modulated by the gut microbiota. To investigate this, we colonized male and female PD transgenic mice (3KL mice) with gut microbiota from a Spanish kindred of familial PD carrying the E46K mutation in the alpha-synuclein gene and compared symptomatic carriers vs. asymptomatic carriers and non-carrier familial controls. Male mice colonized with symptomatic PD microbiota showed increased clasping and cognitive impairment as measured by the Y maze, and females showed cognitive impairment as measured by the novel object recognition test. We investigated changes in the gut microbiome by 16S rRNA sequencing and found treatment, age, and sex contributed to microbiome variance (ADONIS, p<0.001) and identified bacteria that correlated with motor and cognitive function. We also found that mice colonized with symptomatic microbiota had increased microglial expression of Sorl1, a gene previously linked to familial PD. Taken together, these data suggest that the PD gut microbiota influences microglia, motor, and cognitive function and identifies specific bacteria that may mediate this effect.
The gut microbiota has many beneficial functions, including helping break down food, producing vitamins, and protecting us from infections. The gut microbiome can even influence the brain by making neurotransmitters or by changing our immune system. We are investigating whether the gut microbiome can affect Parkinson’s disease. To test this, we recruited a Spanish family with a documented history of an inheritable E46K mutation in the alpha synuclein gene known to cause PD. We collected stool samples from carriers who showed PD symptoms, those who didn’t, and from non-carriers (all from the same family) and transferred the feces into male and female mice. We found that recipients of feces from symptomatic carriers showed worse motor function and worse memory compared to controls. We then identified bacteria that were associated with the memory impairments and motor function observed in the mice. Immune cells of the brain (microglia) were altered by these microbes, suggesting that this may be one way that microbes in the gut can contribute to PD. Overall, our findings suggest that the PD gut microbiota influences microglia, motor, and cognitive function and identifies specific bacteria that may mediate this effect.
