Are Prokinetics for SIBO Useful for Gut Health and Motility?

If, When, and How to Use Prokinetics for SIBO Treatment  

Key Takeaways:

  • Gut motility and SIBO may be related, but there’s debate as to whether motility issues cause SIBO or whether SIBO causes poor motility.
  • Either way, prokinetics are potentially useful pharmaceutical and natural agents that can help the gut to be less sluggish and work more efficiently.
  • The best context for using prokinetics in SIBO is as part of an overall gut healing program that addresses underlying gut dysbiosis and inflammation (both of which can cause low motility).
  • By using a holistic approach, many patients will be able to address their SIBO symptoms without the use of prokinetics.

When you have SIBO, especially if it’s accompanied by a whole lot of unpleasant gut symptoms, you might feel like you’d do anything to feel better faster. 

Antibiotic treatment followed by prokinetics for SIBO is one treatment combination that’s sometimes offered as the easy solution. However, as with most gut-related health issues, there’s rarely a quick fix.

In this article, we’ll look at the role of prokinetics for SIBO and what they can and can’t do for the condition and other gut issues.

Prokinetics for SIBO: man with a stomachache

What Do Prokinetics Do?

Prokinetics are medications or herbal supplements that improve the motility of the gastrointestinal system. Motility is how quickly and efficiently food is moved through the gut.

Two key aspects of gastrointestinal motility are [1 Trusted SourcePubMedGo to source, 2 Trusted SourcePubMedGo to source]:

  • Peristalsis: the downward contractions of the GI tract that occur when it has food in it
  • The migrating motor complex: A wave-like motility pattern stimulated by the hormone motilin that works between meals, when the digestive tract is empty.

Prokinetic medications and natural prokinetics increase downward movement, which can help in conditions where gut motility is abnormal, such as chronic constipation, constipation dominant irritable bowel syndrome (IBS-C) and SIBO.

Prokinetics for SIBO

Are Prokinetics for SIBO Useful for Gut Health and Motility? - Prokinetics for SIBO Landscape L

In SIBO, gut bacteria proliferate in the small intestine rather than the large intestine (ie, higher up the digestive tract than they should). 

Many potential factors can cause or contribute to SIBO. One hypothesis is that slowed gastric emptying and reduced small intestine motility increase SIBO risk because gut contents sit around longer, allowing bad bacteria and fungi to grow [3 Trusted SourcePubMedGo to source].

It’s easy to imagine, then, how prokinetics might help in counteracting SIBO by flushing the contents of the gut downwards. 

However prokinetics often aren’t always the right route for SIBO and IBS symptoms.

To begin with, while poor motility is one possible cause of SIBO, it’s likely that this problem only affects a small subset of individuals, so a treatment aimed specifically at improving motility may miss the boat for the vast majority of SIBO patients.

Even for those who do have slow motility, prokinetics might not necessarily address what’s causing that low motility: often, inflammation or gut dysbiosis.

Even where prokinetics could be helpful, a healthy diet and probiotics should be the first supports for SIBO that underpin any other treatments.

We’ll investigate a bit more where prokinetics might fit into a SIBO treatment plan later. But first, here’s a roundup of common prokinetic medications and natural prokinetics.

Pharmaceutical Prokinetics for SIBO

Name ClassificationEffects
Prucalopride (Motegrity, Resolor), Mosapride, Tegaserod* Serotonin receptor agonistsStimulate peristalsis and normalise motility.
*Tegaserod is older generation and has adverse effects that include cardiac arrhythmia [4]
ErythromycinMacrolide antibioticA 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 [5 Trusted SourcePubMedGo to source]
Metoclopramide, Domperidone*Benzamide-derivative dopamine receptor antagonistsAccelerate gastric emptying in diabetic gastroparesis (incomplete stomach emptying most commonly affecting people with diabetes); acts as an antiemetic (inhibitor of vomiting) [6 Trusted SourcePubMedGo to source]
*Domperidone is no longer routinely available in the USA 
Low Dose NaltrexoneOpioid receptor antagonistInconclusive evidence that in low doses it regulates gut motility and can ease chronic constipation and Crohn’s disease symptoms [7 Trusted SourcePubMedGo to source, 8 Trusted SourcePubMedGo to source]
BethanecholCholinergic agent (mimics the central nervous system neurotransmitter acetylcholine) Used for reflux and gastroparesis in the past, but largely replaced by newer agents [5 Trusted SourcePubMedGo to source, 9]
Prokinetics for SIBO: ginger root and ginger powder

Natural Alternative Prokinetics for SIBO

Iberogast ®Herbal — ingredients include bitter candytuft, angelica root and chamomileEquivalent efficacy in treating functional dyspepsia to the now defunct prokinetic drug Cisapride (withdrawn in the USA due to side effects) [10 Trusted SourcePubMedGo to source, 11 Trusted SourcePubMedGo to source, 12 Trusted SourcePubMedGo to source]
GingerCulinary spiceSoothes nausea [13 Trusted SourcePubMedGo to source]; mixed evidence that it speeds stomach emptying [14 Trusted SourcePubMedGo to source, 15 Trusted SourcePubMedGo to source]
Peppermint oilEssential oil May help improve motility, reduce inflammation, and gut microbiota [16 Trusted SourcePubMedGo to source, 17 Trusted SourcePubMedGo to source, 18 Trusted SourcePubMedGo to source, 19 Trusted SourcePubMedGo to source]
TriphalaAyurvedic laxative medicineImproved the frequency and consistency of bowel movements in one clinical trial [20]
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 [21 Trusted SourcePubMedGo to source]

SIBO, Motility, and Autoimmunity

Gut motility issues, including faster or slower transit times, can result from an autoimmune problem occurring in the aftermath of an infection such as food poisoning, a stomach virus, or traveler’s diarrhea. 

In this case, the immune system system can damage cells called interstitial cells of Cajal, which play an important role in regulating motility [22 Trusted SourcePubMedGo to source].

Testing for antibodies known as anti-CdtB antibodies and anti-vinculin antibodies can assess if this sort of immune damage has occurred. However, it is not something I tend to do routinely with my SIBO/IBS patients, as it isn’t always that informative.

For example, a 2017 observation study found that the presence of both these antibodies tended to predict IBS-D (diarrhea predominant IBS) reasonably well. However, 26.7% of people with IBS-C (constipation dominant IBS) still had the antibodies, as did 16.3% of people with no symptoms at all [23 Trusted SourcePubMedGo to source].

Similarly, a 2021 study found no statistical difference between the levels of anti-CdtB antibodies among those with functional GI disorders (including IBS) and healthy individuals [24 Trusted SourcePubMedGo to source].

Overall, it’s likely that the autoimmunity-driven dysmotility theory behind IBS and SIBO has been overstated.

The Role of Inflammation and Dysbiosis

While the autoimmunity hypothesis above suggests that dysmotility problems in the gut cause SIBO, there’s also some evidence that the other way round is true — ie, the gut bacteria imbalances and inflammation that come with SIBO cause gut dysmotility issues [25 Trusted SourcePubMedGo to source].

This is another reason why tackling inflammation and dysbiosis is so important for those with SIBO and IBS. For example:

  • An observational study found inflammation to be a major driver of motility problems in inflammatory bowel disease (Crohn’s disease patients) [26 Trusted SourcePubMedGo to source].
  • Studies in which gut biopsies are tested in the lab show that inflammation interferes with the ability of the human small intestine to contract properly [27 Trusted SourcePubMedGo to source].
  • In patients with type 2 diabetes, the presence of SIBO has been associated with delayed gut transit, pointing to an association between gut microbial dysbiosis, GI dysmotility, and metabolic disorder [28 Trusted SourcePubMedGo to source].

Rather than hopping straight to prokinetics for SIBO or IBS, it’s therefore a good idea to deal with inflammation and gut bacteria imbalances and allow your gut motility apparatus (and your overall gut health) to repair naturally. This approach has worked best for most of my patients and fits with research that shows the interstitial cells of Cajal (ICC) —intestinal cells involved in healthy gut motility — can repair themselves in about 6 months even after significant autoimmune damage [29 Trusted SourcePubMedGo to source, 30 Trusted SourcePubMedGo to source, 31 Trusted SourcePubMedGo to source].

Diet and Lifestyle Alternatives to Prokinetics

The most effective approach to dealing with SIBO and IBS symptoms is a comprehensive gut healing program. Remember, prokinetics are not for everyone, and they cannot replace good nutrition and lifestyle habits.

The most important part, and the first place to start, is your diet. Giving extra support to your gut microbiome with the right probiotics will also help, as of course will a healthy, physically active lifestyle.

Let’s have a look at these one by one:

Healthy Eating (the Low FODMAP Diet)

Prokinetics for SIBO: FODMAP Food List infographic by Dr. Ruscio

Cutting down on inflammatory processed foods and sugar will help with gut symptoms almost straight away. Healthy whole foods such as vegetables, whole grains, and lean proteins are the basis of most healthy eating regimens that reduce inflammation and control blood sugar. But for SIBO and IBS in particular, the low-FODMAP diet may be most pertinent.

A low FODMAP diet cuts out specific troublesome carbohydrates that would otherwise feed the gut bacteria that cause gas and bloating. Low FODMAP diets have been shown to be very effective at improving SIBO and IBS symptoms [32 Trusted SourcePubMedGo to source, 33 Trusted SourcePubMedGo to source, 34 Trusted SourcePubMedGo to source, 35 Trusted SourcePubMedGo to source].

One review of 10 clinical trials found that the low-FODMAP diet resulted in several positive changes in the microbiome, and in overall gut health, including [32 Trusted SourcePubMedGo to source]:

  • A less leaky gut 
  • Reduced inflammation
  • Reduced histamine (a marker of an overzealous immune system)

An advantage of the low-FODMAP diet is that though it may be somewhat restrictive at first, as your SIBO improves, you should gradually be able to reintroduce and tolerate foods that were previously problematic.

Probiotic Support

To complement positive diet changes, adding a daily probiotic supplement is the next really useful step. Despite some reports to the contrary, probiotics are a safe, excellent and well evaluated treatment for SIBO [36 Trusted SourcePubMedGo to source].

For example:

  • A meta-analysis summarizing 18 clinical trials concluded that probiotics are an effective treatment for SIBO. Specifically, probiotics reduced bacterial overgrowth and hydrogen concentrations and improved symptoms including abdominal pain [36 Trusted SourcePubMedGo to source].
  • A pilot study found probiotics to be more effective than antibiotic treatment for SIBO [37 Trusted SourcePubMedGo to source].
  • Another study found that probiotics work better in patients with both IBS and SIBO as compared to those who have IBS without SIBO [38 Trusted SourcePubMedGo to source].

A Three-Prong Approach

3 Probiotics for Gut Balance infographic by Dr. Ruscio

Research has observed that multi species probiotics work best, for example for alleviating IBS symptoms [39 Trusted SourcePubMedGo to source, 40 Trusted SourcePubMedGo to source]. Some of the best success we’ve seen in the clinic with SIBO patients has been when these three types of probiotics were administered at the same time:

These three types of probiotics work together like the legs of a three-legged stool. If the stool only has one or two legs, it’s likely to be unstable. With three legs, the stool is able to stay upright.

Exercise

Physical activity is another important way to ensure healthy gut motility and beat constipation. Being on your feet and moving around tends to encourage proper gut contractions [41 Trusted SourcePubMedGo to source, 42 Trusted SourcePubMedGo to source, 43 Trusted SourcePubMedGo to source].

Each week, you should try to fit in 150 minutes of moderate or 75 minutes of vigorous exercise. This can be spread over several short (5-10 minute) bursts if you prefer.

There is also good evidence that exercise improves the bacteria in your gut microbiome [44 Trusted SourcePubMedGo to source].

When to Consider Prokinetics 

White pills and an orange pill bottle

If some of your symptoms still remain after you’ve made diet and lifestyle changes and been taking probiotics for a month or so, it’s time to consider other ways to support your gut.

In the phased protocol described in Healthy Gut, Healthy You, antimicrobials are the next logical step, with prokinetics something to consider after that.

Antimicrobials

Given the ability of antibiotics and antimicrobials (even natural versions) to blast bad bugs [45, 46 Trusted SourcePubMedGo to source], it might be tempting to opt for microbials earlier on in your gut treatment pathway. However, lots of clinical experience and good practice guidelines from around the world suggest otherwise. 

For example, the 2021 IBS treatment guidelines from the British Society of Gastroenterology and Romanian Society of Neurogastroenterology reflect that the treatment order should be diet. probiotics and then antimicrobials [47 Trusted SourcePubMedGo to source, 48 Trusted SourcePubMedGo to source].

Antimicrobials that can help SIBO patients include the following:

  • Rifaximin (a conventional antibiotic)
  • Oregano
  • Berberine
  • Artemisinin
  • Caprylic acid

You can work with a practitioner to find out which antimicrobial works best for you. If you decide this is Rifaximin, you’ll need a doctor’s prescription for this pharmaceutical antibiotic. However many patients prefer to work with natural antimicrobials, such as ginger, peppermint oil and other herbals, that can still have potent effects [46 Trusted SourcePubMedGo to source] but may be less likely to contribute to antibiotic resistance [49 Trusted SourcePubMedGo to source].

Prokinetics

The theory behind using prokinetics after antibiotics is that they help to maintain good motility and prevent bad bacteria from building up again. If you have SIBO-associated IBS-C (which tends to correlate with a positive methane breath test) you are likely a good candidate for prokinetics.

Evidence that supports the use of prokinetics for SIBO and other motility problems includes:

  • A review of randomized controlled trials (RCTs) that found several different prokinetics accelerated gastric emptying and reduced upper gastrointestinal symptoms [6 Trusted SourcePubMedGo to source]. 
  • A 2013 expert review that concluded prucalopride and mosapride were helpful for treating IBS-C [50 Trusted SourcePubMedGo to source].
  • Research showing long-term users of PPI (proton pump inhibitor) medications had a faster gut motility and a lower risk of SIBO (associated with long-term PPI use) when they add prokinetics to their regimen [51 Trusted SourcePubMedGo to source].
  • Six RCTs found that patients receiving prucalopride were more likely to experience an increase in complete spontaneous bowel movements (to at least three per week) than those who received a placebo [52].

However not all the research is clear-cut, nor are prokinetics a silver bullet. For example: 

  • A 2011 systematic review of eight RCTs (424 patients with constipation or IBS-C) found that the prokinetic cisapride demonstrated no clear benefit over placebo [53 Trusted SourcePubMedGo to source].
  • In an observational study, patients with various gut symptoms were prescribed the prokinetic low-dose naltrexone. The study found that of the 85 patients with IBS and SIBO [7 Trusted SourcePubMedGo to source]:
    • 15 (17.6%) got much better 
    • 32 (37.6%) got moderately worse 
    • 1 (1.2%) became much worse
  • Treatment of SIBO with prokinetics (following antibiotics) extended the period before bacterial regrowth, but relapse still occurred within 5–7 months (versus two months later if no prokinetic was used [54 Trusted SourcePubMedGo to source].

Which prokinetic to choose for SIBO, and when, is something you can work out with a practitioner or by following the great-in-8 protocol. If you are going it alone, remember that you won’t get the stronger acting pharmaceutical prokinetics without a prescription. Many people find they prefer to start with gentle natural prokinetic agents such as ginger, anyway.

The Bottom Line 

Prokinetics help improve gut motility and can be of help in SIBO, but a good effect isn’t guaranteed, nor should prokinetics be the first or only treatment. Diet changes, probiotics and antimicrobials should come first. SIBO relapses can happen even if you do use prokinetics and reducing these relapses and eventually reaching a point where your gut is completely well again takes a multi-pronged approach. For expert help tailoring prokinetics and SIBO treatment to your needs, consider a consultation at my functional medicine center

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