Antimicrobial Agents: When and How to Use Them for a Healthy Gut

Antimicrobial agents: ginger tea with lemon and mint

Gut issues can bring up many different kinds of symptoms, like brain fog, fatigue, and inflammation, and more. Along with gastrointestinal symptoms, dealing with these issues on a daily basis can be exhausting. 

Often, these gut and systemic symptoms are a result of microbial infections that create or contribute to an imbalance in the good and bad bacteria in the microbiome. An imbalance in the gut microbiome is known as dysbiosis. Small intestinal bacterial overgrowth (SIBO), parasites, and candida are just a few types of microorganisms and imbalances that can cause a disturbance in the gut microbiology. 

For some people, rebalancing the gut is simply a matter of making diet and lifestyle changes that allow the good bacteria to recover and balance to be restored. Probiotic therapy may also help increase beneficial bacteria and crowd out harmful microbes. But other people need antimicrobial agents to tackle the invaders and regain gut health. 

In this article, we’ll define antimicrobial agents, when you should use them, how to incorporate them into your therapeutic regimen, possible side effects, and other tips you should know. 

What Are Antimicrobial Agents?

Antimicrobial agents: Gut Bugs That Cause Imbalances infographic by Dr. Ruscio

Antimicrobial agents kill microbes or prevent them from growing. There are four categories of antimicrobials [1]: 

  • Antibiotics (antibacterial agents) 
  • Antifungals
  • Antivirals
  • Antiprotozoals (antiparasitics). 

When dealing with bacterial overgrowth, antibacterial herbs can work in two ways: 

  • They may be bactericidal, meaning they actually kill harmful bacteria by destroying bacterial ribosomes, enzymes used in reproduction, or the cell wall.
  • They may be bacteriostatic, meaning they prevent or regulate bacterial growth.

Both of these components can help reduce bacterial overgrowth and keep harmful bacteria in check. 

Antibiotics vs. Antimicrobials

The difference between antimicrobial drugs and antibiotics is that antibiotics are exclusively antibacterial. They’re intended to kill bacteria specifically. For example, common prescription antibiotics you may recognize include penicillin, methicillin, cephalosporins, tetracycline, streptomycin, aminoglycosides, and quinolones, among many others. These antibiotics are often prescribed for bacteria such as escherichia coli (e. Coli), staphylococcus aureus (a staph infection), salmonella, and streptococcus (causes strep throat). 

But antimicrobials have a more broad-spectrum pharmacology. They include compounds that are not only antibacterial but can also be antiparasitic, antifungal, and antiviral ​​[2]. 

When to Use Antimicrobial Agents

When patients present with symptoms like fatigue, brain fog, low mood, inflammatory diseases, and autoimmune conditions, it’s highly likely the gut microbiome has an imbalance, whether it’s a fungal overgrowth, SIBO, or parasitic worms [3, 4, 5]. 

So why not start these patients immediately on antimicrobial therapy to help get rid of any potential infection? 

The reason is because without a healthy foundation, antimicrobials are less likely to be effective and may be more likely to lead to side effects. And, in many cases, individuals can restore gut balance through diet and lifestyle alone. 

Therefore, the use of antimicrobials should only come as a third-line option, after implementing diet and lifestyle changes and probiotic therapy. The order of this approach is well-researched and backed by scientific study. For example, the British Society of Gastroenterology and Romanian Society of Neurogastroenterology reflect this treatment order in their 2021 IBS treatment guidelines [6, 7].

So, the treatment we recommend will often look like this: 

Antimicrobial agents: 3 Steps for Gut Health infographic by Dr. Ruscio

Let’s take a closer look at each step of this reset, support, remove approach. 

Start With Diet

Before using antimicrobial agents, we have to lay a good gut foundation with an anti-inflammatory and immune friendly diet. Eliminating foods that can trigger inflammation and an immune response alone can go a long way towards improving your overall health. Ideally, by implementing the right diet, you may not need antimicrobial treatment.  

The Paleo diet is one anti-inflammatory diet that eliminates these triggering foods, like gluten-containing grains and dairy products, and replaces them with nutrient-rich animal proteins, fruits, vegetables, and gluten-free grains and starches. 

For many people, this will allow the gut to start rebuilding. But if the Paleo diet doesn’t improve your symptoms as much as you would like, you can also try a low-FODMAP diet. Low-FODMAP restricts foods that feed bacteria, which may help reduce symptoms further if you have some kind of bacterial overgrowth in play. This diet has been shown to be very effective for gut issues like IBS [8, 9, 10, 11].

Do You Need an Elemental Diet? 

For some patients, replacing their regular diet with an elemental formula can help the gut heal. This can be done for as many or as few meals as you wish. For many people, just replacing breakfast or lunch provides that critical resting time for the gut to repair itself. 

Studies on the effectiveness of elemental diets for addressing SIBO, IBS, IBD, and other gastrointestinal diseases are strong [12, 13, 14, 15, 16, 17, 18].

Antimicrobial agents: probiotic pills inside and outside a jar

Next, Try Probiotic Therapy

After changing your diet, probiotics are the next step in rebuilding your gut microbiome. Probiotics can create powerful and lasting changes to the microbiota in your gut and may even have some antimicrobial activity on their own. Look at just a few of the peer-reviewed studies on probiotic therapy: 

  • For SIBO patients, probiotic therapy was shown to significantly improve bacterial overgrowth and reduce abdominal pain, according to a meta-analysis and systematic review of 18 studies ​​[19]. 
  • In one study, probiotics were found to be even more effective than metronidazole (an antibiotic) in the treatment of SIBO [20].
  • In IBS, multi-strain probiotics improved abdominal pain and discomfort [21].
  • S. boulardii (a healthy fungus) is effective in treating parasites in the gut, including  giardia, amoebas, and Blastocystis hominis [22].
  • In terms of overall gut health, probiotics can lower inflammation, improve the balance of gut bacteria, fight pathogens, clean up toxic compounds, and support digestive function [19, 23, 24].

Furthermore, the research suggests that better results are achieved when you take multiple species of probiotics at one time. For example, two systematic reviews and meta-analyses indicate that multi-species probiotics were more effective than single-species probiotics for treating IBS [25].

Most probiotics fit into one of three different categories: 

  • Multi-strain Lactobacillus and Bifidobacteria blends
  • Saccharomyces boulardii (a beneficial yeast)
  • Soil-based probiotics, usually Bacillus species.

For the most microbiome benefits, we recommend taking one of each type (triple probiotic therapy). 

Introducing Antimicrobial Agents

If you’ve reset your diet and tried probiotics for at least a couple of weeks but your symptoms aren’t improving much, you may consider adding antimicrobial agents. Depending on how long it takes to zero in on your ideal diet, the full healing process could take anywhere from 1-3 months. 

The great thing about antimicrobial herbs is that you don’t need to exactly identify which pathogen is at the root cause of your issues. This is because most of these herbs work on a broad-spectrum level, addressing multiple pathogens at the same time. 

Many medicinal plants and herbs are antibacterial, antiparasitic, antifungal, and antiviral — truly antimicrobial [26]. 

Coconut oil in jar and wooden spoon

Benefits of Antimicrobials

Beyond killing microbes, antimicrobial agents have some pretty impressive physical and mental health benefits. Here are some research-based examples: 

  • Cognitive function: In a systematic review, berberine was found to prevent brain damage and enhance cognitive function, potentially preventing dementia associated with diabetes [27].
  • Performance/mental fatigue: By taking encapsulated peppermint oil, people given a cognitively strenuous task experienced improved performance and reduced fatigue while completing the task [28].
  • Inflammation: A 2019 study showed that berberine appeared to decrease C-reactive protein levels in the blood, which indicates reduced inflammation [29].
  • SIBO: A study determined that a combination of herbal antimicrobials, including berberine and oil of oregano, was found to reduce small intestinal bacterial overgrowth just as well as the antibiotic Rifaximin [30].

Effective Antimicrobial Agents

Unfortunately, there is still a lack of research in human clinical trials when looking at how antimicrobial herbs affect human health. However, there have been many animal and laboratory studies. 

We know that pharmaceutical antibiotic intervention can have excellent benefits for conditions like SIBO, and the research supports this. If we have herbal counterparts to these pharmaceutical antibiotics that appear to have similar bactericidal effects, we can infer that they will have a similar clinical outcome as the pharmaceutical drug interventions, hopefully with fewer side effects. 

Here are some of the most well-researched herbal antimicrobials:


Active IngredientsAntimicrobial EffectOther BenefitsSources
Thymol and carvacrol (in oregano oil)Antibacterial, antiviral, antifungal, antioxidant, insecticidal Pain-relieving and liver-protective effects have been noted. May act as an antidepressant. Antibacterial effects against harmful bacillus species have also been reported.[31, 32, 33]


Active IngredientsAntimicrobial EffectOther BenefitsSources
Berberine, which naturally occurs in various plants, including Oregon grape and goldensealEffective antimicrobial agent and anti -inflammatory May inhibit dementia by preventing brain damage. Beneficial effect on high blood cholesterol and triglycerides. Improved diarrhea symptoms in IBS; may also help H. pylori eradication and reduce colorectal adenoma recurrence. [27, 34, 35, 36, 37, 38]

Sweet Wormwood (Artemisia Annua)

Active IngredientsAntimicrobial Effect Other BenefitsSources
ArtemisininAntimicrobial, antiparasitic,antifungal and anti-inflammatory; has gut microbiome modulating effects. An FDA-approved derivative of artemisinin achieved faster parasite clearance combined with a sulfonamide than sulfonamide alone. Has antimalarial effects.[39, 40, 41, 42, 43]

Peppermint Oil

Active IngredientsAntimicrobial EffectOther BenefitsSources
Various: Includes limonene, cineole, menthone, menthol, pulegone, and carvone Antifungal, antimicrobial, and antiparasitic propertiesVery effective in easing pain and bloating in IBS. Boosts alertness. Peppermint oil inhalation had an antibacterial effect alongside multidrug therapy in tuberculosis. [28, 44, 45, 46, 47]

Caprylic Acid

Active IngredientsAntimicrobial EffectOther BenefitsSources
Caprylic acid: a fatty acid that occurs in large quantities in coconut oilAntibacterial, antifungalMay have neuroprotective effects. May benefit chronic upper respiratory tract infection, tooth infection, and cytomegalovirus infection.[48, 49]
Doctor giving pills to a patient

Pharmaceutical vs. Natural Antimicrobials

Some cases may call for the careful use of antibiotics or antifungal drugs, such as treatment of certain infectious diseases or bacterial infections. For example: 

  • SIBO treatment may require a round of Rifaximin or a combination of Rifaximin and neomycin [50, 51].
  • Fluconazole is a common antifungal used for acute candida infections.
  • Flagyl can help destroy protozoa (parasites). 

However, using prescription antimicrobial medications typically requires you to know exactly what pathogen or problem you’re dealing with. If you’re wrong about the type of infection, the drug may not help. This is because most prescription antimicrobials are designed to attack a specific type of bacteria, fungus, or parasite. This is why broad-spectrum herbal compounds are more forgiving if you’re unsure of the type of pathogen causing your symptoms [26].

Still, pharmaceutical interventions have their place. Review the pros and cons of natural vs. conventional options with your provider.  

Possible Side Effects of Antimicrobials

Because they can be so powerful, use antimicrobials with caution and pay close attention to your response as you begin. You should know the potential side effects of antimicrobial use. 

What Is Die Off? 

“Die off” is a reaction that can occur when bad bacteria or microbes die inside your body, increasing toxicity and causing a number of symptoms. You may experience: 

  • Headaches
  • Digestive upset
  • Increased fatigue
  • Flu-like symptoms

A die-off reaction shouldn’t last longer than a few days to a week, similar to the time it takes to fight a cold. On one hand, it’s no fun to experience these symptoms, but on the other hand, it means your antimicrobial regimen is working. 

However, there’s no reason to suffer through a die-off reaction. If you’re really feeling unwell, you can lower your antimicrobial dosage, take the same dose at longer intervals or stop completely for a short period to give your body a chance to recover and adapt. Consult your doctor before making any changes to your antimicrobial regimen. 

If you persist through the symptoms but your reaction doesn’t go away after a week, you may be allergic to something in the formula you’re taking. In this case, stop taking any antimicrobials for at least a few days and see how you feel. You can reintroduce antimicrobials one at a time to see what you had a problem with, or you might simply need a lower dose. Again, consult your doctor to make these adjustments. 

Bacterial Resistance

Bacteria, parasites, fungi, or viruses can become resistant to antimicrobial treatment. Resistant strains of harmful bacteria are a huge public health concern when infections become more difficult to treat and the risk of disease increases [52].

Intrinsic antibiotic resistance occurs when a microbe is inherently protected from an antimicrobial agent. For example, gram-negative bacteria have an extra outer membrane that protects the bacterial cell wall from some antibiotics. Of the types of bacterial resistance, this one is less serious. 

Acquired antibiotic resistance is when a microbe develops drug resistance over time, becoming immune to an antibiotic or antimicrobial that once could destroy it. One example of this is methicillin-resistant Staphylococcus aureus, or MRSA. 

The worst case scenario is a pathogen that becomes multi-drug resistant to any drug treatment we can throw at it. The antibiotic vancomycin is the antibiotic of last resort in Western medicine, but some bacteria have already developed resistance to it [1]. 

Ultimately, we can boil down this issue to two points: 

  • The bad news is that antimicrobial resistance is basically inevitable due to the adaptability and diversity of microorganisms as well as the prevalence of pharmaceutical antibiotics in healthcare over the last several decades. 
  • The good news is that antimicrobial herbs can help with these resistant microorganisms, since they have a more broad-spectrum mode of action than pharmaceutical agents. Antimicrobial herbs can also be combined and rotated to prevent antimicrobial resistance. 
Balanced stones by the sea

Find the Right Balance

Once you’ve adjusted your diet and lifestyle and built up your good gut bacteria with probiotics, antimicrobial agents can help reduce or eliminate bad or overgrown microbes in your gut. They are often the turning point in resolving stubborn health issues caused by bacterial infections or other pathogens such as parasites and fungi.

If you’re interested in starting an antimicrobial regimen, consider booking an appointment with one of our experienced practitioners at the Ruscio Institute for Functional Medicine.


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