Can Prokinetic Agents Help SIBO and Gut Symptoms?

Written by Dr. Ruscio on August 24, 2021

Your Complete Guide to the Pros and Cons of Prokinetics

What Are Prokinetic Agents?|
Gut Motility and Dysmotility|
SIBO|
Dysbiosis, Inflammation and Gut Motility|
Gut Healing Strategies|
Follow-up Therapies|
When and How to Try Prokinetics|
Recommended Products|

Key Takeaways

Pharmaceutical and natural prokinetic agents are designed to improve gut motility (get a sluggish gut moving).
There’s been a tendency for these to be considered a “silver bullet” in the treatment of SIBO patients.
In fact, motility problems may often go away of their own accord if underlying gut dysbiosis and inflammation are treated.
Prokinetic agents can help with motility, but only if still needed when the fundamentals of diet and probiotic therapy are in place.

Within the world of functional medicine, the use of pharmaceutical or natural prokinetic agents in patients with SIBO (small intestine bacterial overgrowth), IBS (irritable bowel syndrome), and other gastrointestinal disorders is hotly debated.

Prokinetics are a complex topic, and there are some gaps in the research. It’s easy to get bogged down in the details. But if you’re struggling with unpleasant gut-related symptoms, you’ll mainly just want to know if prokinetics will work for you or not.

In this article, we’ll walk you through the evidence and help you to come to a considered decision about using them.

What Are Prokinetic Agents?

Prokinetics agents are pharmaceutical and natural substances that support gut motility — the healthy downward movement of food through your digestive tract.

Prokinetic agents are popularly used for treating reflux diseases like heartburn (where food and acid move upwards from the stomach into the esophagus). But as well as treating gastroesophageal reflux, it’s also become more common to use them for conditions like SIBO or IBS. This is based on the idea that slow movement through the gastrointestinal tract may be an underlying cause of these conditions.

Examples of prokinetic drugs include tegaserod, prucalopride, macrolide and mosapride. However natural prokinetic agents have also been identified. For example, probiotics, curcumin, melatonin, peppermint oil, ginger, and some ayurvedic medicines may all aid gastric motility.

Natural Prokinetic Agents

Name	Description	Effects
Probiotics	Live bacteria	Shown to improve constipation, stool frequency, intestinal transit time, and IBS symptoms, both alone and when combined with mosapride [1, 2, 3, 4, 5, 6].
Chinese herbal medicine	Specific Chinese herbs including modified Runchang-Tang, modified Chaihu Shugan, and modified Xiaoyao San	More effective than prokinetic drugs at improving constipation and indigestion [7, 8, 9, 10, 11].
Iberogast ®	An herbal blend — ingredients include bitter candytuft, angelica root and chamomile.	Equivalent efficacy in treating functional dyspepsia to the now defunct prokinetic drug Cisapride (withdrawn in the USA due to side effects) [12, 13, 14].
Peppermint oil	Essential oil	May help improve motility, reduce inflammation, and improve gut microbiota [15, 16, 17, 18].
Curcumin	Bioactive substance found in turmeric	May improve digestive symptoms of IBS, ulcerative colitis, and peptic ulcer disease [19, 20].
Japanese herbal medicine	Specific Japanese herbs including rikkunshito (RKT), dai-kenchu-to (DKT), and hange koboku to (HKT)	Shown to improve constipation, motility, gastric emptying, reflux, and digestive symptoms [21, 22, 23, 24, 25].
Melatonin	Hormone available as a supplement	Shown to reduce abdominal pain and other digestive symptoms, potentially in part by improving motility [26, 27, 28].
Ginger	Culinary spice	Soothes nausea [29]; mixed evidence that it speeds stomach emptying [30, 31].
Triphala	Ayurvedic laxative medicine	Improved the frequency and consistency of bowel movements in one clinical trial [32].
Prodigest ®	Standardized combination of artichoke and ginger extracts	Found to be 24% better than placebo at improving motility after a meal, suggesting efficacy as a prokinetic agent [33].

Pharmaceuticals With Prokinetic Effects

Name	Classification	Effects
Prucalopride (Motegrity, Resolor), Mosapride, Tegaserod*	Serotonin receptor agonists	Stimulate peristalsis and normalise motility. *Tegaserod is older generation and has adverse effects that include cardiac arrhythmia [34]
Low-dose Erythromycin	Macrolide antibiotic	A low dose stimulates the secretion of motilin hormone, which in turn activates the cyclic, recurring motility pattern (the migrating motor complex, or MMC) that occurs in the stomach and small bowel during fasting [35]
Metoclopramide, Domperidone*	Benzamide-derivative dopamine receptor antagonists	Accelerate gastric emptying in diabetic gastroparesis (incomplete stomach emptying most commonly affecting people with diabetes); acts as an antiemetic (inhibitor of vomiting) [36] *Domperidone is no longer routinely available in the USA
Low Dose Naltrexone	Opioid receptor antagonist	Inconclusive evidence that in low doses it regulates gut motility, and can ease chronic constipation and Crohn’s disease symptoms [37, 38]
Bethanechol	Cholinergic agent (mimics the central nervous system neurotransmitter acetylcholine)	Used for reflux and gastroparesis in the past, but largely replaced by newer agents [35, 39]

Gut Motility and Dysmotility

To understand why you might need prokinetics, it’s important to understand what good gut motility means.

In a normal healthy gut, peristalsis is the distinctive pattern of propulsive smooth muscle contractions. This propels foodstuffs down the esophagus into the stomach via the lower esophageal sphincter into the small intestine and then via the ileocecal valve into the large intestine (colonic region).

If those peristaltic movements aren’t working properly and become sluggish, things can get out of whack in the GI tract — this is known as dysmotility.

For an analogy, think of flowing water in a river or stream, and then compare it with a stagnant pond. Good motility helps keep your gastrointestinal ecosystem, or microbiota, in balance. But just as standing water can foster bacterial growth, when food is moving too slowly, it can cause bacteria and fungi to overgrow.

Poor Gut Motility Might Not Be a Main Cause of SIBO

The idea that poor gastrointestinal motility can be a factor in SIBO and/or IBS isn’t in dispute. However, it’s important not to run away with the idea that these conditions are exclusively, or even primarily, a motility disorder.

My contention is that poor motility is actually far less common in IBS and SIBO that those within the SIBO community suggest.

For example, other documented causes of/risk factors associated with SIBO that aren’t to do with impaired with motility documented include [40]:

Low stomach acid affecting the stomach’s ability to digest or degrade harmful intestinal bacteria
Low levels of digestive enzymes
Chronic pancreatic insufficiency
Autoimmune disorders.

Factors other than poor gut motility that can contribute to IBS include:

Gut dysbiosis (as a result of poor diet, stress, antibiotic use and other lifestyle factors [41, 42]
A bout of food poisoning (estimated to trigger between 5% and 32% of IBS cases) [43]
A leaky gut [44, 45]
Immune disruptions [46, 47]
Altered serotonin levels (serotonin is a chemical messenger and one of the body’s most important signaling chemicals for digestion) [48]

Given all these possible contributing factors to IBS and SIBO, by only honing in on gut motility as the issue (and by implication, prokinetics being the answer), we may miss important pieces of the puzzle.

Dysbiosis, Inflammation and Gut Motility

A more holistic approach is to consider the overall dysbiosis and inflammation that underlies most cases of SIBO and IBS, which are themselves highly interrelated [49].

One interpretation of the data on motility and SIBO is that reduced gut motility precedes gut symptoms and predisposes people towards developing SIBO [50]. However, it’s more likely that the existing inflammation and gut bacteria imbalance associated with SIBO and IBS actually cause reduced gut motility [51].

For example, one observational study found inflammation to be a major driver of motility problems in Crohn’s disease patients [52].

Excess blood sugar can also contribute to inflammation, and, in turn, motility issues [53, 54].

One theory is that inflammation interferes with the ability of intestinal cells called interstitial cells of Cajal (ICC) — involved in healthy gut motility — to repair themselves.

If you are in the early stages of SIBO treatment, you will likely have low motility as a result of gut dysbiosis and inflammation that disrupt the gut motility apparatus — but that doesn’t necessarily mean you have a functional motility problem that requires prokinetic therapy.

What I have consistently found in clinical practice is that by remedying the underlying gut dysbiosis and damping down inflammation, we can resolve the motility issues and improve symptoms of SIBO and IBS without needing much other intervention.

Effective Gut Healing Strategies

One small observational study in patients whose IBS/SIBO was successfully treated with antibiotics did find that a popular prokinetic medication (low dose erythromycin) staved off a relapse longer than patients who did nothing (five months versus two months) [55].

However, we need to weigh the risk-to-benefit ratio when using prokinetic medications. No studies have been done to show how long non-pharmaceutical alternatives stave off SIBO recurrence, and this approach could be more effective.

I’ve found that a more well-rounded and multifaceted approach to gut healing is the best way to go before leaping to prokinetic agents. For nearly all my patients, motility issues can be resolved with this approach, without using prokinetics.

When approaching gut health more holistically, a step-by-step approach beginning with diet and probiotics generally works best.

Low FODMAP Diet

Any diet that cuts down on sugary and highly processed foods and focuses instead on whole foods, such as leafy greens and lean proteins, can help to calm inflammation and begin getting your gut in better shape.

However, for IBS and SIBO in particular, you might want to go straight to the low FODMAP diet. It has been shown to be particularly helpful in these conditions [56, 57, 58, 59].

Low FODMAP diets cut out or minimize certain types of fermentable, bacteria-feeding carbs (FODMAPs) that can flare SIBO and IBS symptoms. High FODMAP foods include common foods like dairy, honey, onions, and wheat. You may not have to cut them out forever, but doing so while you’re experiencing the worst IBS/SIBO symptoms may help you to feel better.

An observational study involving 13 IBS patients and 13 healthy controls found that a low FODMAP diet also increased the densities of endocrine cells that secrete serotonin. This in turn stimulates motility and speeds up transit time in both small and large intestines [60]. We can’t read too much into this small study, but it does seem to suggest that a gut healing diet might in itself act like a prokinetic agent.

Probiotic Therapy

Your second vital strand in easing gut symptoms and re-establishing gut health is taking a probiotic supplement. There’s a wealth of research showing just how beneficial probiotics can be:

One recent clinical trial (330 patients) found that probiotics significantly reduced abdominal pain and bloating in IBS patients. Subjects also experienced a significant normalization in stool consistency and quality of life [61].
Many other high-quality studies agree that probiotics improve IBS symptoms, including gas, diarrhea, and constipation, bloating, abdominal pain [4, 62, 63, 64, 65, 66, 67].
With reference to intestinal motility, various human trials and a systematic review and meta-analysis of randomized, controlled trials found that specific probiotic species and strains could decrease gut transit time by 12 hours (i.e. improve motility) [1].
A meta-analysis summarizing 18 clinical trials also showed that probiotics are an effective treatment for SIBO, reducing bacterial overgrowth and hydrogen concentrations, and improving symptoms [68, 69, 70, 71].

Follow-up Therapies

If you don’t have complete symptom relief after sorting your bases of diet and probiotics, another couple of approaches that may work include antimicrobials and an elemental diet.

These approaches both help to correct gut bacteria imbalance and remove lingering bad bacteria.

Antimicrobials

Rifaximin is an antibiotic medicine that can help clear SIBO infections [72, 73]. More natural but often as effective are plant-based antimicrobials [74] such as oregano oil (active ingredient carvacrol) [75], berberine [76], and caprylic acid [77].

Elemental Diet

An elemental diet provides all the nutrients in a predigested form, thereby giving your system a rest and allowing it to heal. An elemental formula can be used to replace all your meals over a block of several days, or just to replace one or two meals on a regular basis.

Research has shown that elemental diets even used 50% of the time can significantly gut symptoms and flares [78].

How and When to Try Prokinetic Agents

You should by all means consider taking a prokinetic if, after trying all the steps above, you still have issues with gut issues or SIBO. You may be a candidate if you have constipation-dominant IBS [79, 80]. IBS-C tends to be more associated with bacteria that produce methane, which slows down motility and could play a role in constipation [81].

If you could benefit from a pharmaceutical prokinetic — which can have a stronger action — you’ll need to discuss this with a doctor and get a prescription.

However you may prefer a plant-based prokinetic such as Iberogast or peppermint oil (peppermint conveniently also doubles up as an antimicrobial) [82]. These may be less effective in certain cases, but may still help to achieve the effect of gently improving the motility of your gut.

Pharmaceutical drugs also tend to have more frequent and severe side effects than natural treatments. Mosapride, lubiprostone, cisapride, and other prokinetic drugs have been linked to side effects including headaches, dizziness, insomnia, and increased digestive side effects including nausea, heartburn, diarrhea, and constipation (in other words, many of the symptoms you’re trying to get rid of!). In some cases, prokinetic drugs can also lead to more serious side effects.

Tying It All Together

Prokinetic agents do have their place, but there’s been a tendency to jump to them too fast for SIBO treatment. Most cases of SIBO and IBS aren’t caused by poor gut motility. More likely, the poor motility is a result of the inflammation and dysbiosis that are part and parcel of these conditions.

By tackling the underlying issues with a comprehensive gut healing regimen, you’re likely to get better results in the long runYou find a lot more detail on healing your gut in my book, “Healthy Gut Healthy You.” Or, you might consider a personal consultation for more in-depth help with gut-related health issues.

Dr. Michael Ruscio is a DC, Naturopathic Practitioner, researcher, and clinician. He serves as an Adjunct Professor at the University of Bridgeport and has published numerous papers in scientific journals as well as the book Healthy Gut, Healthy You. He also founded the Ruscio Institute of Functional Health, where he helps patients with a wide range of GI conditions and serves as the Head of Research.

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