Homo sapiens are the only species of humans still existing, as far as we know. Sapiens became the "sensible, shrewd, knowing" species of humanoids (the Homo genus) with assistance from the gut microbiota that evolved alongside and within Homo sapiens, providing metabolites and assisting the gut-brain axis to aid brain expansion and function. This review discusses coevolution, how dietary and environmental changes have influenced the importance of the gut microbiota, the microbiome-gut-brain axis (MGBA) and related epigenetic changes, and how current procedures and products may alter the beneficial commensal relationship and contribute to increased incidence of disorders such as asthma, autoimmune diseases, obesity, and neuropathology. Immune and endocrine homeostasis are tightly linked to the MGBA, and industrialization, by dispersing more chemicals into the environment, is upsetting the balance. Although brain laterization influences on immunity and neurological disorders are reported, there is no definitive linkage between brain hemisphere effects on gut microbiota or the MGBA. Brain laterality (left/right hemisphere differences) affects physical and mental stress sensitivity, but linkage of MGBA and metabolites to autoimmune neurological diseases remain speculative. Loss of microbiota diversity and altered proportions of certain bacterial species due to environmental stressors may lead to increased numbers of opportunistic and pathogenic bacteria (dysbiosis) creating metabolites having fewer beneficial and more detrimental effects across multiple host organs. Diet, environmental toxicants, and stress are presented as influences on the current increased incidence of some immune-associated disorders, autoimmune diseases, and neuropathy. Increased toxic insults are hypothesized to coincide with immune disorders based on gut microbiota changes. Within the CNS itself, complement- and immunoglobulin-mediated synaptic pruning has emerged as a convergent mechanism linking peripheral immune dysregulation to synaptic vulnerability in neurodegenerative and neuropsychiatric disease, suggesting that enteric nervous system and MGBA disruption may act upstream of these processes. Genetic and genomic aspects of the host-microbiome relationship are also discussed.
