Malfunction of a Hypothetical Evolved Microeukaryote Microbiome: Birth-Initiated Dysregulation of Immune System, Brain, and Gut

Although autoimmune conditions are normally recognised by their physical symptoms, on further investigation signs of neuropsychiatric disease may become apparent. While it is possible that the one actually causes the other, it is noteworthy that a similar correspondence can also be traced to the so-called gut-brain axis, perhaps indicating a deeper relationship between the three nominally independent variables of immune system, brain, and gut. Increasingly, as this “triple plague” of related conditions (autoimmunity, poor mental health, and weight gain) has begun to resemble an avalanche, intense speculation has focused on the so-called microbiome: that collection of unicellular pro- and eukaryotes, viruses and mobile genetic elements present, to a greater or lesser extent, at many sites around and inside the body. Primarily for reasons of accessibility and ease of analysis, most effort has focused on the bacteria, i.e., the bacteriome, but unfortunately with little rationale. By contrast, our work was based on the premiss that the microbiome, “our microbes” has evolved to be an intergenerational part of animal immune systems, helping to protect successive generations of multicellular entities against external microbes. Analysis further suggested that key microbes should be the more flexible microeukaryotes, while the concomitant, diverse, bacteriome is able to express mobile genetic elements. In summary, the evolved nature of these key microbes means that they should be transferred at birth, i.e., as a maternal microbial inheritance working alongside the parental genetic inheritance of the individual. As antigenic information is carried within the body by sentinel cells, the most succinct suggestion would be that intergenerational information is carried by means of a microbial version of such cells, perhaps taken up by the neonate gut as a form of inoculation to become what could be classed as an “immune-gut-brain triangle”. If so, it would be their failure in microbe-hostile environments that accounts for the often early-onset epidemiology of what has been termed “dysbiosis”: potentially eczema in the infant; autism in toddlers; and type 2 diabetes in primary school children. Significantly, however, in this hypothesis disease is not a problem of the organs themselves, but of their communication with the brain. Accordingly, the so-called placebo effect could be due to a temporary improvement in brain-centred communication.