Migrating Motor Complex
The motility controller
Rebooting the Migratory Motor Complex .
If you have dealt with Small Intestinal Bacterial Overgrowth, Intestinal Methanogen Overgrowth, or some version of Irritable Bowel Syndrome; chances are that you have heard that you need to address the Migrating Motor Complex to help reduce bloating, gas, and general irregular bowel funciton.
The migrating motor complex (MMC) is characterized by waves of gastrointestinal smooth muscle contractions during the fasting state. The MMC occurs in a series of phases, including a quiescent phase, a phase of smooth muscle oscillations, a phase of intermittent smooth muscle contractions, and a phase of continuous sweeping contractions (up to 11 per minute). The MMC is important because it provides mechanical and chemical cleansing of the empty stomach and intestines. Impaired function of the MMC can result in retention of gastric or intestinal contents, bacterial overgrowth, and subsequent symptoms of functional bowel disorders.
The interaction between the MMC and bacterial overgrowth appears to be bidirectional. Whereas impaired MMC allows for overgrowth of bacteria, dysbiotic bacteria can, conversely, produce toxins that inhibit motility. In the case of Campylobacter jejuni infection, antibodies to cytolethal distending toxin B (CdtB) and vinculin damage the interstitial cells of Cajal and subsequently disrupt gastrointestinal motility.[1]
There is also an important interaction between the MMC and neuroendocrine function. The MMC cycle is mediated by vagal nerve activity as well as by a positive feedback interaction between motilin and 5-hydroxytryptamine (5-HT).[2]
According to this model, release of 5-HT promotes motilin release, which further drives release of 5-HT until 5-HT granules are depleted. Antagonists of 5-HT3 (e.g., ondansetron) inhibit the gastric MMC but do not affect the intestinal MMC, and antagonists of 5-HT4 (e.g., piboserod) inhibit both the gastric and intestinal MMC.[3] Stress plays a significant role in the function of the MMC, as reduced vagal activity impairs the MMC.[4]
Finally, the presence of food in the duodenum halts release of motilin, and therefore stops the sequential waves of the MMC. When patients consistently graze on small meals at frequent intervals, they lose the cleansing action of the MMC. Meals must be spaced at least 4-5 hours apart to allow for the complete MMC cycle. In addition, there should be no food for at least 8-12 hours overnight.
Our understanding of the MMC came initially from the study of gastroparesis (in which there is a dramatic slowing of digestive motility), but its relevance has extended to functional bowel disorders. The first step in rebooting the MMC in patients with IBS is teaching them about proper meal spacing. The second step is balancing vagal tone. The third step is evaluating and treating SIBO or other forms of intestinal dysbiosis. These steps should lead to healthy function of the MMC and dramatic improvement in functional bowel symptoms.
There are many nutritional, herbal, and functional treatments that support motility and migrating motor complex. In Europe the most researched motility treatment is a patented blend of herbs called Iberogast (which is composed of Iberis amara, Angelica, Chamomile, Caraway fruit, St. Mary’s thistle, Balm Leaves, Peppermint Leaves, Celandine, and Licorice Root). Like many natural medicines the effect of this blend is thought to be multifactorial including having an affinity for binding to 5HT3 and 5HT4 receptors, opioid receptors, and muscarinic receptors. It is also thought to have mast cell stabilizing activity. Its broad spectrum approach is likely the reason why it can be effective.
Other strategies for regulating the migrating motor complex includes using amino acid and neuropeptide supplements such as 5-HTP, GABA, and melatonin. These compounds help to regulate motility by acting on enterochromaffin cells, afferent signaling pathways, and by increasing the luminal content of serotonin. In addition, these supplements also help with HPA/CNS stabilization via coordination of the brain/gut axis.
Low Dose Naltrexone can also be used to help regulate motility. Our understanding of the mechanism is evolving but it likely that it helps to restore patterns in the gut by acting as a weak agonist on opioid receptors thereby reducing visceral sensitivity. It is also postulated that low dose naltrexone modulates inflammation in the gut but this mechanism is poorly understood at this time.
In Ayurvedic medicine, the staple herb Terminalia chebula (known as Triphala) has been used traditionally to promote motility and also in gastroparesis as a prokinetic. In rodent studies, it has proved more effective in reducing gastroparesis than metoclopramide, a common anti-gastroparesis drug. As of now we do not understand the mechanism of Triphala in the gastrointestinal tract, however its antimicrobial and anti-inflammatory actions are well understood.
Finally, Zingiber officinalis (ginger root) is often used as a prokinetic to increase with motility and cleansing waves. The use of ginger root has been studied for nausea associated with gastric hypomotility which involves a temporary dysfunction of the integrated network of cholinergic M3 and serotonergic 5- HT3/5-HT4 receptors. The major chemical constituents of the ginger roots lipophilic extracts such as [6]-gingerol, [8]-gingerol, [10]-gingerol, and [6]-shogaol do modulate all these receptors. This likely explains ginger’s effect on improving the migrating motor complex. (Lazzini, Polinelli, Riva, Morazzoni, & Bombardelli, 2016)
I have put together a list of some of the better migrating motor complex agents here .
[1] Pimentel M, Morales W, Pokkunuri V, et al. Autoimmunity Links Vinculin to the Pathophysiology of Chronic Functional Bowel Changes Following Campylobacter jejuni Infection in a Rat Model. Dig Dis Sci. 2015;60(5):1195-1205. [abstract]
[2] Takahashi T. Interdigestive migrating motor complex -its mechanism and clinical importance. J Smooth Muscle Res. 2013;4999-111. [abstract]
[3] Nakajima H, Mochiki E, Zietlow A, Ludwig K, Takahashi T. Mechanism of interdigestive migrating motor complex in conscious dogs. J Gastroenterol. 2010;45(5):506-514. [abstract]
[4] Greydanus MP, Vassallo M, Camilleri M, Nelson DK, Hanson RB, Thomforde GM. Neurohormonal factors in functional dyspepsia: insights on pathophysiological mechanisms. Gastroenterology. 1991;100(5 Pt 1):1311-1318. [abstract]