How Antibiotics Increase IBD Risk

by Wayne Persky

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Recently published research shows that antibiotics damage the protective mucus layer (of the epithelia) in the intestine, independent of microbiota changes (Sawaed, et al., 2024).1 This appears to be an important discovery for microscopic colitis (MC) patients, as MC, like other IBDs, involves chronic inflammation of the intestinal lining. The disruption of the mucosal barrier (by an antibiotic treatment) could potentially worsen MC symptoms by exposing the intestinal epithelium to bacteria, triggering immune responses and exacerbating inflammation. Most of us are well aware of this problem, and many of us have been aware of it for many years. But now, the medical community is officially aware of it, also.​

Crohn's disease (in humans) resembles Johne's disease (in ruminants).

For many years after MC was first medically described, researchers suspected that IBD (especially Crohn's disease) might be caused by a bacterium similar to the one that causes Johne's disease in ruminants (Mycobacterium avium subspecies paratuberculosis [MAP]). But no research studies have ever been able to prove that connection. While this new discovery supports the probable role of pathogenic bacteria in the actual physical damage to the mucosal barrier (that initiates the development of IBD), the smoking gun that provides the opportunity for those bacteria to gain access to the mucosal barrier has been shown to be the use of antibiotics.​

Whether antibiotics initially cause IBD remains to be proven.

But it's obvious that antibiotic use could certainly inadvertently increase the risk of aggravating IBD (including MC), due to compromised mucus integrity. And the epidemiological evidence from our shared experiences on the discussion and support forum associated with our website, clearly shows that many of us have initially developed MC soon after undergoing one or more antibiotic treatments.

Compromising epithelial mucus production leads to inflammation.

The research provides evidence that antibiotic use allows bacterial infiltration into the intestinal wall by reducing mucus production. For MC patients, who already suffer from inflammation in the colon, this could mean that antibiotics may lead to further inflammation, worsening diarrhea and other symptoms. And because MC involves immune reactions in the colon, antibiotic-induced bacterial penetration could heighten immune activation, making the disease more challenging to manage.

This discovery suggests the need for drastic changes in antibiotic use.

Obviously, this discovery suggests that current treatment strategies for infections in IBD patients, need to be reconsidered. Physicians may need to weigh the risks of using antibiotics more carefully, considering alternative treatments or preventive measures to protect the mucosal barrier when antibiotics are necessary. But in addition to that, since antibiotic treatments obviously may increase the risk of developing IBD for anyone (although that remains to be proven), new guidelines for the use of any antibiotics that affect the digestive system should be developed, to suppress the increasing prevalence of IBD.

So what are our options if our doctor says we need an antibiotic?

Depending on the details of the particular health issue that is prompting our doctor to make that recommendation, there may be some leeway in the choice of antibiotics. But if the reason for using an antibiotic is a life or death matter, there may not be much leeway — we may just have to do what we have to do, and hope for the best.

Let's consider two categories for these antibiotic selections that are least likely to trigger a reaction for MC patients.

1. Antibiotics that should be safe based on theoretical considerations​.

1. Narrow-Spectrum Antibiotics — Narrow-spectrum antibiotics target specific bacteria and tend to have less impact on the gut and systemic health compared to broad-spectrum antibiotics. This makes them a safer option for MC patients. However, their safety still depends on the specific drug and individual response. They are effective for targeted bacterial infections, but their utility is limited to bacteria they are specifically designed to treat. For infections that involve resistant bacteria or multiple types, their efficacy may be lower.

2. Penicillin Derivatives (for example, Amoxicillin, Amoxicillin-Clavulanate) — Penicillin derivatives like amoxicillin are generally well-tolerated and are considered among the safer antibiotics for people with gut issues, including MC. However, combinations like amoxicillin-clavulanate (Augmentin) may cause “mild” gastrointestinal disturbances, so they should be used cautiously. Penicillin derivatives are highly effective for a broad range of bacterial infections, including respiratory, skin, and soft tissue infections. Amoxicillin, in particular, is a first-line treatment for many infections.

Despite that endorsement based on theoretical considerations, it should be noted that our shared experiences on our discussion forum suggest that amoxicillin causes many of us to react with diarrhea, although that doesn't necessarily mean that the antibiotic is triggering an MC reaction. Diarrhea is a labeled side effect of many, possibly most, antibiotics.

3. Cefuroxime — Cefuroxime is a second-generation cephalosporin with a relatively narrow spectrum of activity. While safer than some broad-spectrum cephalosporins, it can still have moderate effects on the gut, so it should be used with caution by MC patients. It is effective against respiratory tract infections, skin infections, and urinary tract infections (UTIs). It’s not as broad-spectrum as other cephalosporins but remains a reliable option for many bacterial infections.

4. Macrolides (for example, azithromycin, clarithromycin) — Macrolides are often used in penicillin-allergic patients and have a lower impact on the gut microbiome compared to some other antibiotic classes. They are generally considered safer for MC patients, but prolonged use can still pose some risks to gut health. Macrolides are effective for respiratory infections, certain skin infections, and atypical bacterial infections. Azithromycin is particularly known for its shorter duration of therapy and fewer side effects.

5. Nitrofurantoin — Nitrofurantoin is minimally absorbed in the gut, meaning it has limited systemic effects, including on the gastrointestinal system. This makes it a very safe choice for MC patients, especially when treating urinary tract infections (UTIs). Nitrofurantoin is highly effective for treating UTIs but is not useful for infections outside the urinary tract, which limits its broader applicability.

6. Rifaximin — Rifaximin is minimally absorbed systemically and acts locally in the gut. It is often used to treat conditions like irritable bowel syndrome (IBS) and small intestinal bacterial overgrowth (SIBO) without significantly disrupting the gut microbiome. It’s considered one of the safest antibiotics for gut-sensitive patients, including those with MC. Rifaximin is highly effective for gastrointestinal-related infections but is not a broad-spectrum antibiotic for systemic infections. Its use is mainly limited to gut infections and conditions like traveler’s diarrhea or hepatic encephalopathy.

When rifaximin first became available, many gastroenterologists were prescribing this antibiotic as a treatment for MC. And for some patients, it did indeed seem to control the symptoms for a week or two. But following that brief respite, symptoms virtually always returned. It was originally labeled for "traveler's diarrhea", and that's probably it's best use.

7. Fluoroquinolones (for example, levofloxacin, ciprofloxacin) — Fluoroquinolones are associated with a range of serious side effects, including risks of tendinitis, and neuropathy. Fluoroquinolones are broad-spectrum antibiotics that are highly effective against a wide range of infections, including respiratory, urinary, and gastrointestinal infections. However, their high efficacy comes with significant safety trade-offs, especially for long-term or recurrent use. Note that the U.S. Food and Drug Administration (FDA) has imposed regulations that require black box warnings against the possibility of tendon or neurological damage due to the use of fluoroquinolones (Tanne, 2008, July 19).2​

Key Takeaways

• Nitrofurantoin and Rifaximin are the safest options (from a theoretical viewpoint) for MC patients, with minimal effects on gut health, though they are limited in their scope of use (UTIs for Nitrofurantoin and gut-related conditions for Rifaximin).
• Penicillin derivatives and Macrolides are generally safe and effective choices for a wide range of infections, making them good options when broader coverage is needed.
• Fluoroquinolones despite their high efficacy, are risky for MC patients due to their significant side effects, and they should only be used when certain precautions (described below) are taken.​

2. Antibiotics that have been shown to be safe by personal experience.

Note that these are also included in the "theoretically safe" category above, but they have been found to be safe for most of us by our personal experiences.

• Ciprofloxacin — We have found Cipro to be safe and effective against a broad range of infections, including gut issues, many dental issues, UTIs, and respiratory infections. Cipro virtually never triggers an MC reaction for any of us. In fact, it will typically stop an MC reaction and calm the gut while it is being used, although the symptoms will almost always return after the treatment is ended, if the proper diet changes have not been made.

The black box warnings on fluoroquinolone labels are there for a reason.

​So please don't write the warnings off as "trivial". Ciprofloxacin (similar to the other fluoroquinolones) depletes magnesium, and as we have learned in the school of hard knocks, magnesium deficiency opens the door to many adverse consequences. Similarly, magnesium diminishes the effectiveness of Cipro. Therefore, although it's important for us to replenish our magnesium reserves while we're taking Cipro, we have to be careful not to take the Cipro and a magnesium supplement at the same time, because if we do, each one will antagonize the other. In other words, we need to allow enough time after taking Cipro for it to be absorbed into our bloodstream, before taking any magnesium supplements.

 These are uncharted waters.

Although the following viewpoint has never been proven by medical research, (because it has never been trialed or researched), epidemiological evidence suggests that the risks reflected in the black box warnings regarding the use of fluoroquinolones, are due to the effects of magnesium deficiency.​

Consequently, it appears that individuals who use any of the fluoroquinolones are at risk of tendon damage, or neurological damage, for example, if they allow their magnesium level to be depleted. Those who maintain an adequate magnesium level, don't appear to have an increased risk of tendon or neurological damage. But please remember that since this has never been proven by medical research, it must be regarded strictly as speculation. And just as there are never any guarantees that published medical research findings are valid proof that a medication will work well for everyone, there certainly are no guarantees that any statement based on speculation is valid for everyone (or anyone, for that matter).

​ Never take Cipro and a magnesium supplement at the same time.

Because of the fact that Cipro and magnesium both antagonize each other, the possibility of mutual damage must be avoided by carefully spacing out the timing between taking the antibiotic and a good magnesium supplement. For safety (and maximum effectiveness), they should be taken at least three or four hours apart. And remember that anyone who chooses to use Cipro as an antibiotic treatment, should definitely be taking a good magnesium supplement according to these directions, in order to prevent the possibility of incurring either tendon or neurological damage, (unless we want to risk the FDA telling us, "See, we told you so.")

• Azithromycin (Z-pak) — We have found that for most of us, azithromycin is a safe choice for treating respiratory infections, many dental issues, and dental procedures, certain skin infections, and certain bacterial infections. However, it's not a broad-spectrum antibiotic, so it's uses are someone limited.

For dental procedures, consider:

Ciprofloxacin (not for patients who are magnesium deficient)
Azithromycin
Amoxicillin
Clindamycin (for penicillin-allergic patients, although the risk of a reaction will be increased)
​Cefuroxime

For sinus infections, consider:

Ciprofloxacin (not for patients who are magnesium deficient)
Azithromycin
Amoxicillin
Cefuroxime or Cefdinir

For skin infections or an infected wound, consider:

1. Topical Antibiotics (First Choice)
​

• Mupirocin
• Bacitracin and Neomycin
  
  

2. Oral Antibiotics (When Topicals Are Not Sufficient)

• Ciprofloxacin (not for patients who are magnesium deficient)Azithromycin
• Cephalexin
• Clindamycin
• Sulfamethoxazole-Trimethoprim (Bactrim) (particularly skin infections caused by MRSA)​

For UTIs, consider:

Prevention Strategies:

• Hydration — Drinking plenty of water helps flush bacteria from the urinary system.
• Urinate Regularly — Don’t hold urine for long periods; frequent urination can help clear bacteria from the bladder.
• Hygiene — Wiping from front to back after using the toilet helps prevent bacteria from entering the urethra.
• Cranberry Products — Cranberries contain compounds that may prevent bacteria from adhering to the bladder walls.
• D-mannose Supplements — This sugar is thought to prevent certain bacteria (like E. coli) from sticking to the bladder lining, and can help toprevent recurrent UTIs.
• Probiotics — Some probiotics, like Lactobacillus, may help maintain a healthy balance of bacteria in the urinary tract and reduce the likelihood of infection.
• Avoid Irritants — Avoiding irritants like certain soaps, douches, or feminine hygiene sprays can help maintain urinary tract health.
• Urinate After Intercourse — This can help flush out any bacteria that may have entered the urethra during sex​

​Safer Treatment Options:

1. Non-Antibiotic Approaches:

• D-mannose
• Cranberry Extract
• Uva-ursi (Bearberry): (This herbal supplement has been used to treat UTIs, but it should be used cautiously, as long-term use can have side effects.)

2. Targeted Antibiotic Use:

• Nitrofurantoin
• Fosfomycin
• Short-course therapy — If antibiotics are necessary, healthcare providers might recommend short-course antibiotics (e.g., 3-day regimens) to minimize the overall exposure and reduce the risk of antibiotic resistance or impact on the gut.

For major surgery, consider:

1. Pre-Surgical Prophylactic Antibiotics

• Cefazolin (Ancef)
• Cefuroxime

​2. For Penicillin-Allergic Patients

• Clindamycin
• Vancomycin

3. Metronidazole
4. Ampicillin-Sulbactam (Unasyn)
5. Gentamicin

We can't always avoid the use of antibiotics.

While it's always best to minimize the use of antibiotics, and avoid them whenever possible, in situations where we have no choice but to use them, we can often pick a product that will minimize our risk of an MC flare, or other complications. But in a life-threatening situation, where a safe option is not available, we have no choice but to do what we have to do, and hope for the best possible outcome. And remember that while this list of (hopefully) safer options may work for many of us, it's probably not going to be safe for all of us, because were all different.

References

1. Sawaed, J., Zelik, L., Levin, Y., Feeney, R., Naama, M., Gordon. A., . . . Bel. S. (2024). Antibiotics damage the colonic mucus barrier in a microbiota-independent manner. Science Advances, 10(37), p 4119. Retrieved from https://www.science.org/doi/10.1126/sciadv.adp4119

2. Tanne, J. H. (2008, July 19). FDA adds "black box" warning label to fluoroquinolone antibiotics. BMJ, 337(7662), a816. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2483892/