Human gastrointestinal (GI) tract microbiome-derived pro-inflammatory neurotoxins from Bacteroides fragilis: Effects of low fiber diets and environmental and lifestyle factors

Over the last decade, our understanding of the immense contribution of GI-tract microbiome to human physiology and host metabolic functions has increased dramatically, yet progress is limited by the sheer complexity and dynamics of these microbial communities [3,81]. Microorganisms of the human GI-tract microbiome are now generally appreciated as playing some critical role in the maintenance of health and the development of disease, however the complexity and diversity of this ‘dispersed organ system’, and commensal and symbiotic relationships with human host cells, particularly with host cells of the central nervous system (CNS) remains incompletely understood. Neurotoxins detrimental to the normal structure, function and signaling properties of brain cells: (i) may be acquired directly via naturally-occurring, plant growth- and plant yield-promoting factors or processed components of ingested foodstuffs; (ii) from the environment; (iii) from the individual lifestyles that we live; and also (iv) from the neurotoxic exudates derived from thousands of species of stressed GI-tract resident microbes. Diet, environment and lifestyle are inextricably linked when considering ‘hologenome’ aspects of a highly networked ‘metaorganism’ and metagenomics factors with the most recent findings that microbiome-derived neurotoxins can strongly contribute to human diseases from intestinal and systemic inflammation, to obesity to schizophrenia and to Alzheimer’s disease (AD) [21,27–33,37–40]. For example, in fiber-deprived diets which can be strongly impacted by environmental and lifestyle choices certain GI-tract abundant Gram negative bacilli such as B. fragilis appear to strongly proliferate, increasing both their potential and abundance for the synthesis and release of neurotoxins by mass action alone. Importantly, especially against a background of unwise and unhealthy environmental and lifestyle choices, some of the most potent neurotoxins known can be a significant and a continuous ‘life-long’ source from the diet, in part through an insufficient supply of dietary fiber and the maintenance, support and proliferation of dysbiotic microbes that maintain their persistent and continual residence in the human GI-tract microbiome.