Abstract
Accumulating clinical- and scientific research-based evidence is driving our increased awareness of the significance of the human microbiome (HM) to the healthy and homeostatic operation of the human central nervous system (CNS). HM communities occupy several different but distinct microbial ecosystems on and within the human body, including nasal, oral, and otic cavities, the surface of the skin and the urogenital and the gastrointestinal (GI) tracts. The complex symbiotic inter-relationship between the GI-tract microbiome and its host is strongly influenced by diet and nutrition, and when optimized can be highly beneficial to food digestion, nutrient intake, and immune health (1–6). For example, dietary composition ultimately affects the structure, organization, function, and speciation of the HM occupying the GI tract, in part by supplying multiple substrates for microbial metabolism. Typical Western diets containing high fat–cholesterol, low amounts of soluble and insoluble fiber, and sugar- and salt-enrichment not only impart deleterious nutrition but also dietary constraints on the HM. This in turn impacts the supply of microbiome-generated molecules absorbed into the systemic circulation for transport into the extensive neurovasculature of the CNS. This short communication will focus on emerging ideas concerning the contribution of the GI-tract microbiome to human neurological disease with emphasis on Alzheimer’s disease (AD) wherever possible.
Highlights
It is the human microbiome (HM) of the GI tract that contains the largest reservoir of microbes in humans, containing about 1014 microorganisms from at least 1000 distinct microbial species, and outnumbering human somatic cells by about 100 to 1 [1, 7]
Of the 55 bacterial divisions currently identified, only two are prominent in mammalian GI-tract microbiota, including the anaerobic Bacteroidetes (~48%) and Firmicutes (~51%), with the remaining 1% of phylotypes distributed amongst the Proteobacteria, Verrucomicrobia, Fusobacteria, Cyanobacteria, Actinobacteria, and Spirochetes, with various species of fungi, protozoa, viruses, and other microorganisms making up the remainder
We list six specific, highly illustrative examples and recent insights into the interactive nature of the HM with a healthy, homeostatic central nervous system (CNS), and examples of a dysfunctional or altered HM contribution to the development of age-associated neurological disease: [1] studies of the enteric nervous system (ENS) in germ-free “gnotobiotic” mice, i.e., those missing their microbiome, indicate that commensal GI-tract microbiota are critically essential for membrane electrical characteristics, including ion fluxes, action potentials, and GI-tract sensory neuron excitability, providing a potential mechanistic link for the initial exchange of signaling information between the GItract microbiome and the autonomic nervous system (ANS), ENS, CNS neuroimmune–neuroendocrine systems [4, 5, 20, 23, 25]; [2] GI-tract-abundant Gram-positive facultative anaerobic or microaerophilic Lactobacillus, and other Bifidobacterium (Actinobacteria) species such www.frontiersin.org
Summary
It is the HM of the GI tract that contains the largest reservoir of microbes in humans, containing about 1014 microorganisms from at least 1000 distinct microbial species, and outnumbering human somatic cells by about 100 to 1 [1, 7].
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