Abstract

We know more about the surface of Mars than we know about the depths of the ocean. David Attenborough, Blue Planet, 2018 The same holds true for the human gut. We can navigate its abysses and study its topography with bathyscopes such as a capsule endoscopy (pill cam) but to a large extent our knowledge of its functional complexity and homeostatic regulation is embryonic. What do we know? We have an inkling that our gastrointestinal tract and its symbionts is existential to our being. I eat, therefore, I am. This Descartian view was expressed by Brillat-Savarin, the father of French gastronomy in the Physiology of Taste (1825) as: ‘Tell me what you eat and I will tell you what you are’. Notionally our gut and symbionts may determine our personality, our intellect and our psyche. Autism,1 schizophrenia,2 attention-deficit/hyperactivity disorder,3 Alzheimer's disease4 and even anxiety5 may be manifestations of our microbial signature and an underlying intestinal dysbiosis. Every individual has a unique flora, with unique speciation and a unique mix. This flora will determine or contribute to our longevity by protecting us from harmful pathogens. Adaptive immunity and surveillance will be established by interaction of our symbionts with immune regulating mechanisms, such as Toll-like receptors6 which may protect us from cancer and autoimmune diseases. Additionally, lifestyle diseases such as obesity and other associated insulin-resistant states such as diabetes types 1 and 2, fatty liver, dyslipidaemia and hypertension, all associated with premature death, have a dysbiotic component.7, 8 All parts of our bowel, the mouth, oesophagus,9 stomach, small intestine10 and colon have their own unique flora. All this is a gift from our mothers. This starts in utero with the swallowing of amniotic fluid,11 but central to the process is vaginal delivery and breastfeeding. Anathema to the establishment of a healthy flora is the early use of antibiotics and possibly antipyretics. As a bonus, our mothers provide us with both a virome, mainly in the form of bacteriophages and a mycobiome (fungi). How these co-passengers contribute to our life course and the phenomenology of our diseases is still to be elucidated. At once the tummy voice came through, It shouted “Hey there! Listen you!” “I'm getting hungry! I want eats!” “I want lots of chocs and sweets!” “Get me half a pound of nuts!” “Look snappy or I'll twist your guts” Whatever's the matter with Mary Jane? She is crying with all her might and main Whatever's the matter with Mary Jane? It can't be rice pudding again. Don't scratch your bum and suck your thumb. Babette Cole, Dr Dog, 1994 The first two examples link food to symptoms of abdominal pain. As such, they are prescient. The much later example from Dr Dog may or may not be good advice. It depends on both parental and medical belief in the hygiene hypothesis. Intestinal parasites may well protect from autoimmune disease.12 Psychiatrists, like mothers, also recognise the centrality of the gut to our existence. They were extraordinarily perceptive in noting that our development is intrinsically linked to our gastrointestinal tract. Of the three stages of infant development, two are gut related. The oral phase relates to sustainability and the anal phase to autonomy. These were recognised by Freud, respectively, as the id and ego predominant. With our evolving understanding of our microbiota, it is possible that Freud scored a trifecta with the possibility that the much less reliable development of a superego (conscience or sentient thought) is also gut related. Paediatric gastroenterologists are lucky. Our domain is the growling, grumbling, volatile, murky, odiferous and largely unexplored gastrointestinal tract of childhood. We serve as Argonauts of the same. Some swerve off on roads less travelled but no less fascinating. The liver and pancreas are much less accessible and even less studied. They hold their own secrets. The Greek legend of the Titan Prometheus forever chained to a rock with an eagle devouring his liver which would regenerate overnight to be devoured again attests to this. Prometheus was eventually freed by Hercules. Two and a half millennia later the equally legendary Thomas Starzl, father of liver transplant, discovered that if you transplant a small liver in a large dog it grows and if you transplant a large liver in a small dog it shrinks.13 We now think this has something to do with insulin-like growth factors and homeobox genes.14 The ancient Greeks believed the liver to be the seat of the soul. This may explain their optimism on Prometheus' part but it is uncannily close to the truth. This issue of the journal explores what we know about the childhood intestinal tract, liver and pancreas. Much is unknown and will be a source of febrile maternal and literary conjecture for millennia to come.

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