Alzheimer’s disease and the microbiome
Frontiers in Cellular Neuroscience
Surjyadipta Bhattacharjee and Walter J. Lukiw
The recognition of the human microbiome (HM) as a substantial contributor to nutrition, health and disease is a relatively recent one, and currently, peer-reviewed studies linking alterations in microbiota to the etiopathology of human disease are few. 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 (CNS). 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 (Forsythe et al., 2012; Collins et al., 2013; Douglas-Escobar et al., 2013; see below). It has been estimated that about 100 trillion bacteria from up to 1000 distinct bacterial species co-inhabit the human GI tract, albeit in different stoichiometries amongst individuals, and the varying combinations and strains of bacterial species amongst human populations might contribute, in part, to “human-biochemical” or “genetic-individuality” and resistance to disease (Aziz et al., 2013; Lukiw, 2013). Interestingly, HM participation in human physiology may also help explain the genomecomplexity conundrum—for example why the 26,600 protein-encoding transcripts in Homo sapiens are far fewer in number, than for example, the rice genome (Oryza sativa; which has about 46,000 functional genes). One thousand different strains of bacteria might be expected to contribute up to 4 × 10 potential mRNAs to the human transcriptome, thus making the human host-plus-microbiome genetic complexity closer to 4,026,600 mRNA transcripts, and a clear “winner” of human genetic complexity over that of rice and other species (Venter et al., 2001; Foster and McVey Neufeld, 2013; Lukiw, 2013). The very recent observation of microbiome-derived small non-coding RNA (sncRNA) and micro RNA (miRNA) translocation and signaling across endothelial barriers, between cells and tissues, and even perhaps between individual species indicates that human neurobiology may be significantly impacted by the actions of HM-mediated sncRNA or miRNA trafficking, and the integration of a cell, tissue or an entire organism into its local environment (Zhao et al., 2006; Alexandrov et al., 2012; Sarkies and Miska, 2013; Reijerkerk et al., 2013; unpublished). This opinion paper ncompasses what we know concerning the contribution of the HM to neurological disease, with specific emphasis on Alzheimer’s disease (AD) wherever possible.