The number of bacterial cells living within the human body is approximately equal
to, or greater than, the total number of human cells. This dynamic population of microorganisms,
termed the human microbiota, resides mainly within the gastrointestinal tract. It
is widely accepted that highly diverse and stable microbiota promote overall human
health. Colonization of the gut with maladaptive and pathogenic microbiota, a state
also known as dysbiosis, is associated with a variety of peripheral diseases ranging
from type 2 diabetes mellitus to cardiovascular and inflammatory bowel disease. More
recently, microbial dysbiosis has been associated with a number of brain pathologies,
including autism spectrum disorder, Alzheimer's disease (AD), Parkinson's disease
(PD), and amyotrophic lateral sclerosis (ALS), suggesting a direct or indirect communication
between intestinal bacteria and the central nervous system (CNS). In this review,
we illustrate two pathways implicated in the crosstalk between gut microbiota and
CNS involving 1) the vagus nerve and 2) transmission of signaling molecules through
the circulatory system and across the blood-brain barrier (BBB). We summarize the
available evidence of the specific changes in the intestinal microbiota, as well as
microorganism-induced modifications to intestinal and BBB permeability, which have
been linked to several neurodegenerative disorders including ALS, AD, and PD. Even
though each of these diseases arises from unique pathogenetic mechanisms, all are
characterized, at least in part, by chronic neuroinflammation. We provide an interpretation
for the substantial evidence that healthy intestinal microbiota have the ability to
positively regulate the neuroimmune responses in the CNS. Even though the evidence
is mainly associative, it has been suggested that bacterial dysbiosis could contribute
to an adverse neuroinflammatory state leading to increased risk of neurodegenerative
diseases. Thus, developing strategies for regulating and maintaining healthy intestinal
microbiota could be a valid approach for lowering individual risk and prevalence of
neurodegenerative diseases.