The human body plays host to a plethora of different microscopic organisms ranging in size and complexity from viruses and bacteria to multicellular, eukaryotic parasitic worms. The bacterial component of the microbiome accounts for roughly 1–3% of body mass with 10 bacteria for every human cell (NIH Human Microbiome Project) and bacterial load is likely to increase with age. Bacteria are found in greatest numbers and variety in the mouth, the gut, and on the skin. Emerging studies indicate that the HM may contribute to the regulation of multiple neuro-chemical and neuro-metabolic pathways through a complex series of highly interactive and symbiotic host-microbiome signaling systems that mechanistically interconnect the gastrointestinal (GI) tract, skin, liver, and other organs with the central nervous system. For example, the human GI tract, containing 95% of the HM, harbors a genetically diverse microbial population that plays major roles in nutrition, digestion, neurotrophism, inflammation, growth, immunity and protection against foreign pathogens.
Bacteria in the mouth, the gut, and on the skin form biofilms. This is a complex ecosystem of different species of bacteria forming a symbiotic whole, enabling the attachment and proliferation of individuals. Biofilm-forming bacteria release a highly hydrated matrix of extracellular polymeric substance, composed of proteins, polyuronic acids, nucleic acids, and lipids. Together bacteria and this matrix form the bulk components of biofilm. Of the estimated 700 oral bacteria identified by DNA, only around 50% have been cultured. The microbiome of the human GI tract is the largest reservoir of microbes in the body, containing about 1014 microorganisms; over 99% of microbiota in the gut are anaerobic bacteria, with fungi, protozoa, archaebacteria and other microorganisms making up the remainder.
As we get older, bacterial load steadily increases as our humoral and cell-mediated immune responses wane in favor of the more primitive, but less efficient, innate immune system. There is growing evidence that the microbiome composition, species identity and combinations, the density and distribution of these bacteria may influence how well we age. Gradually, as the innate immunity predominates over time, certain bacteria may proliferate and trigger more damaging responses. Against a background of rising bacterial load it becomes even more important to maintain the integrity of the blood-brain barrier. Weakening of the blood-brain barrier either, by any predisposing polymorphisms or as a result of conditions that elicit a sustained TNF-α response, may serve to increase the propensity for bacteria or endotoxins to gain access to the brain, trigger neuropathology and alter brain function.