Gastrointestinal Disorders (May 2023)
On the Inheritance of Microbiome-Deficiency: Paediatric Functional Gastrointestinal Disorders, the Immune System and the Gut–Brain Axis
Abstract
Like the majority of non-communicable diseases that have recently gained attention, functional gastrointestinal (GI) disorders (FGID) in both children and adults are caused by a variety of medical conditions. In general, while it is often thought that common conditions such as obesity may cause other problems, for example, asthma or mental health issues, more consideration needs to be given to the possibility that they could both be brought on by a single underlying problem. Based on the variations in non-communicable disease, in recent years, our group has been revisiting the exact role of the intestinal microbiome within the Vertebrata. While the metabolic products of the microbiome have a role to play in the adult, our tentative conclusion is that the fully functioning, mutualistic microbiome has a primary role: to transfer antigen information from the mother to the neonate in order to calibrate its immune system, allowing it to survive within the microbial environment into which it will emerge. Granted that the microbiome possesses such a function, logic suggests the need for a robust, flexible, mechanism allowing for the partition of nutrition in the mature animal, thus ensuring the continued existence of both the vertebrate host and microbial guest, even under potentially unfavourable conditions. It is feasible that this partition process acts by altering the rate of peristalsis following communication through the gut–brain axis. The final step of this animal–microbiota symbiosis would then be when key microbes are transferred from the female to her progeny, either live offspring or eggs. According to this scheme, each animal inherits twice, once from its parents’ genetic material and once from the mother’s microbiome with the aid of the father’s seminal microbiome, which helps determine the expression of the parental genes. The key point is that the failure of this latter inheritance in humans leads to the distinctive manifestations of functional FGID disorders including inflammation and gut motility disturbances. Furthermore, it seems likely that the critical microbiome–gut association occurs in the first few hours of independent life, in a process that we term handshaking. Note that even if obvious disease in childhood is avoided, the underlying disorders may intrude later in youth or adulthood with immune system disruption coexisting with gut–brain axis issues such as excessive weight gain and poor mental health. In principle, investigating and perhaps supplementing the maternal microbiota provide clinicians with an unprecedented opportunity to intervene in long-term disease processes, even before the child is born.
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