A Quick clarification:
I realize that the study was conducted
in vitro, not on patients. So I was theorizing why they even bothered to do so, and I wonder if they already have some good hunches how the
in vivo study (with patients) will turn out. Also, since the article postulated that the excess 11% of the drug that was not absorbed in patients and was still in circulation could be part of the cause of the effect, this could have an in-contact effect on gut bacteria. But the added effect of "messing with" the delicate serotonin balance could be an
additional factor, so that's why I mentioned it. If the drug merely affected the neurology of the colon, it would be less severe than the combination of the two.
Also, I wanted to mention that the link I cited (
https://www.badgut.org/information-centre/a-z-digestive-topics/ibs-and-serotonin/ ) had the most advanced explanation of the gut as "the second brain," detailing the intricate neurology that mimics and closely interfaces with your "upper brain" more than I ever have heard explained. It's worth a read for anyone with ME because of the current research going on:
"The altered bowel function, abdominal pain, and sensitivity symptoms indicative of IBS result from what appears to be a disturbance in the interaction among the gut, the brain, and the Autonomic Nervous System – which includes the Parasympathetic, Sympathetic, and the Enteric Nervous System – or ENS – now recognized as the “
brain below.”
“The status of our knowledge of the enteric nervous system has been, until recently, positively medieval,” said Dr. Michael Gershon, Professor and Chairman, Department of Anatomy and Cell biology at Columbia University, “but in recent times, significant advances in the understanding of this brain in the gut have resulted in a greater appreciation of its importance in clinical medicine, and no more so than in IBS.”
The ENS consists of an extensive network of neurons supported by glia. Enteric glia are analogous to the astrocytes of the CNS. Enteric glial processes encircle large bundles of enteric axons. The small intestine contains about 100 million nerve cells, roughly equal to the number found in the spinal cord.
Two neural plexuses comprise the ENS: a larger, myenteric plexus, positioned between the muscle layers of the muscularis externa, which is home to the neurons responsible for motility. A smaller, submucosal plexus houses sensory cells that talk to the neurons of the myenteric plexus and contain motor nerves cells, which stimulate luminal secretion.
Signals from the brain to the gut play a critical role in maintaining optimal digestive function, reflex regulation of the GI tract, and modulation of mood states.
The ENS can regulate peristalsis and secretion – independently of the central nervous system.
If you cut the central nervous system connection to the gut, the bowel function persists. The ENS relies on a number of neuropeptides and small molecules to regulate both intestinal motility and secretion. Scientific evidence strongly suggests that serotonin – or 5HT – is one of the most important signalling molecules involved in the peristaltic reflex – and that alterations in serotonin signalling may be responsible for IBS symptoms. Ninety-five percent of the serotonin found in the body resides in the gut.
“I first proposed that serotonin was an enteric neurotransmitter in the 1960s,” explained Dr. Gershon, “and by the early 1980s, my suggestion had been confirmed, and teams of scientists determined that serotonin was not only a neurotransmitter but also a signalling molecule that ultimately triggers peristaltic and secretory reflexes. Today, the gut is known to have at least seven different serotonin receptors.”
In order for the gut to govern its own behaviour and trigger any reflexes, it has to sense what is going on in the lumen of the bowel. It does so using two detectors: the intrinsic primary afferent neurons of the intestine (IPANS) and enterochromaffin (EC) cells.
“IPANs are activated by luminal content, such as pressure, nutrients, or acidity and they are the detectors that mobilize the neurons that control mixing and propulsion in the small intestine,” said Dr. Gershon. The large concentration of serotonin in EC cells is located in the basal granules of these cells because the serotonin is secreted into the wall of the gut, not the lumen.
The ECs release serotonin into the underlying connective tissue space, which contains the nerve fibres that express serotonin receptors and thus respond to serotonin.
These receptors include the 5-HT3 receptors known to send signals encoding pain, nausea and other noxious sensations to the CNS. This serotonin release occurs as the result of mucosal stimulation.
The release of serotonin and activation of interneurons within the ENS triggers a cascade of other neurotransmitters, such as acetylcholine and Substance P, which excites peristaltic and secretary reflexes.
“We now have extensive data confirming that serotonin stimulates the peristaltic reflex when it is applied to the mucosal surface and that serotonin is released when peristalsis is initiated. We also know that this reflex disappears when the mucosal actions of serotonin are blocked,” said Dr. Gershon.
The more we know about serotonin’s role in the enteric nervous system, the closer we come toward creating effective therapeutic agents that can manipulate serotonin action and provide symptom relief.
“As the true abundance of neurotransmitters, such as serotonin, in the gut finally become apparent, it has become possible to use the actions of these substances to unlock the secrets of the second brain and to use the data to bring solace to a troubled gut,” explained Dr. Gershon.