Gastrointestinal Disorders (Nov 2022)
Microbiome–Gut Dissociation in the Neonate: Autism-Related Developmental Brain Disease and the Origin of the Placebo Effect
Abstract
While the importance of the intestinal microbiome has been realised for a number of years, the significance of the phrase microbiota–gut–brain axis is only just beginning to be fully appreciated. Our recent work has focused on the microbiome as if it were a single entity, modifying the expression of the genetic inheritance of the individual by the generation of interkingdom signalling molecules, semiochemicals, such as dopamine. In our view, the purpose of the microbiome is to convey information about the microbial environment of the mother so as to calibrate the immune system of the new-born, giving it the ability to distinguish harmful pathogens from the harmless antigens of pollen, for example, or to help distinguish self from non-self. In turn, this requires the partition of nutrition between the adult and its microbiome to ensure that both entities remain viable until the process of reproduction. Accordingly, the failure of a degraded microbiome to interact with the developing gut of the neonate leads to failure of this partition in the adult: to low faecal energy excretion, excessive fat storage, and concomitant problems with the immune system. Similarly, a weakened gut–brain axis distorts interoceptive input to the brain, increasing the risk of psychiatric diseases such as autism. These effects account for David Barker’s 1990 suggestion of “the fetal and infant origins of adult disease”, including schizophrenia, and David Strachan’s 1989 observation of childhood immune system diseases, such as hay fever and asthma. The industrialisation of modern life is increasing the intensity and scale of these physical and psychiatric diseases and it seems likely that subclinical heavy metal poisoning of the microbiome contributes to these problems. Finally, the recent observation of Harald Brüssow, that reported intestinal bacterial composition does not adequately reflect the patterns of disease, would be accounted for if microbial eukaryotes were the key determinant of microbiome effectiveness. In this view, the relative success of “probiotic” bacteria is due to their temporary immune system activation of the gut–brain axis, in turn suggesting a potential mechanism for the placebo effect.
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