Can antibiotics cause a RA flare?

October 14, 2025 •

4 min read

According to a 2019 study published in Nature, the risk of rheumatoid arthritis (RA) flare was significantly increased in patients using sulfonamide and trimethoprim antibiotics within the previous 12 months. This finding highlights a potential link between antibiotic use and heightened disease activity, raising important questions about whether and how antibiotics can cause a RA flare.

Quick Summary

Antibiotics may disrupt the gut microbiome, which can potentially influence immune responses and lead to an increase in rheumatoid arthritis (RA) flare-ups. The direct cause-and-effect relationship is complex due to confounding factors like the underlying infection itself, which is a known trigger for flares.

Key Points

Microbiome Disruption: Antibiotics can disturb the gut microbiome, potentially increasing autoimmune activity and triggering an RA flare.
Specific Antibiotics: Research has linked sulfonamide and trimethoprim antibiotics to a higher risk of RA flares in the months following treatment.
Confounding Factors: The underlying infection, not just the antibiotic, can be a major trigger for RA flares, complicating research into causation.
Not Always a Trigger: Some antibiotics, like minocycline, have historically been used to treat RA due to their anti-inflammatory properties.
Talk to Your Doctor: Never stop a prescribed antibiotic without consulting your rheumatologist, as treating the infection is critical.
Other Triggers Exist: Many factors besides medication, such as stress, poor sleep, and illness, are known to cause RA flares.

Emerging research has shed light on a complex relationship between antibiotics and rheumatoid arthritis (RA) activity, particularly regarding the risk of flares. While definitive causation is not established, a growing body of evidence suggests an association that is likely mediated through the gut microbiome.

The Role of the Gut Microbiome

Your gut microbiome is a diverse ecosystem of microorganisms that plays a critical role in regulating the immune system. In autoimmune conditions like RA, the immune system is overactive and attacks healthy tissues.

Microbiome disruption: Antibiotics, while essential for treating bacterial infections, can also kill beneficial bacteria in the gut, leading to a state of imbalance known as dysbiosis. This disturbance can persist for months or even a year after a short course of treatment.
Immune system modulation: Changes in the gut microbiota can affect local and systemic immunity. This modulation can potentially increase autoimmune activity and inflammation, which are the hallmarks of an RA flare.
Molecular mimicry: Some researchers hypothesize that antibiotics can alter the body's microbial environment in a way that leads to the immune system attacking the body's own proteins through a process called molecular mimicry.

Specific Antibiotics and Flare Risk

While observational studies have suggested a link between antibiotic exposure and increased RA risk generally, some research has focused on specific types of antibiotics and their potential impact on flares.

Sulfonamide and Trimethoprim

A 2019 study published in Nature used a large UK patient database to examine the association between various antibiotics and RA flares. The study's key findings highlighted a specific link:

Increased flare risk: The use of sulfonamide and trimethoprim was associated with a 70% increased risk of an RA flare in the 1–3 months following treatment, with the risk remaining elevated for up to 12 months.
Gut/urinary microbiome link: Researchers hypothesized that this delayed onset of flares is mediated through the gut or urinary microbiomes.

Other Antibiotics

Other antibiotics have been investigated, but evidence of a direct causal link to flares is inconsistent.

Tetracycline: A recent Mendelian randomization study found no causal link between tetracycline use and RA risk after adjusting for confounding factors. This class of drugs, including minocycline, has also been historically used to treat RA due to anti-inflammatory properties, illustrating the complex picture.
Other classes: Observational studies have sometimes noted associations between other classes, including amoxicillin, ciprofloxacin, and clindamycin, and RA symptoms, but more research is needed.

Distinguishing Between the Infection and the Medication

One of the most significant challenges in studying the link between antibiotics and RA flares is the confounding factor of the underlying infection itself. Infections, especially respiratory ones, are known to be potent triggers for RA flares.

The Confounding Issue

Infection-induced flares: When a person with RA contracts a bacterial infection, their immune system ramps up to fight it. This increased immune activity can independently trigger a flare.
Observational bias: Observational studies may show a correlation between antibiotic use and flares simply because the antibiotic is a marker for an infection that was the true cause of the flare. It becomes difficult to separate the effects of the drug from the effects of the illness.
Unresolved questions: Research is still ongoing to determine the relative contribution of infections versus antibiotic-induced microbiome changes in driving RA activity.

Managing Your Health and Flare Triggers

For individuals with RA, understanding and managing potential flare triggers is key to maintaining remission.

Common RA flare triggers include:

Stress (emotional or physical)
Infections or other illnesses
Overexertion
Poor sleep
Smoking
Weather changes
Medication issues, such as stopping a prescribed drug

Comparison of Antibiotic Use and RA Risk


Aspect	Observational Studies (e.g., 2019 BMC Medicine study)	Mendelian Randomization (MR) Studies (e.g., 2025 study)
Conclusion	Found a higher risk of RA incidence or flares associated with antibiotic exposure.	Found no causal relationship between antibiotic use and RA risk after adjusting for confounders.
Methodology	Analyze large databases of patient health records to find correlations.	Use genetic variants as proxies for exposure to reduce confounding factors inherent in observational data.
Strengths	Can identify associations that warrant further investigation.	Better at establishing causal links by minimizing confounding.
Limitations	Prone to confounding bias (e.g., underlying infection, smoking).	Results may not be generalizable to all populations and have their own methodological constraints.
Interpretation	Antibiotic use may be a risk factor, possibly through microbiome disruption, but causation is not proven.	Observed associations may be significantly influenced by confounding factors and are not necessarily causal.

Conclusion

While a definitive causal link demonstrating that antibiotics cause a RA flare has not been established, a significant association exists, particularly for certain antibiotic classes. This relationship is complex and likely involves the disruption of the gut microbiome, which can influence immune system activity. It is also critical to recognize that the underlying infection requiring the antibiotic is a known trigger for RA flares and can be a major confounding factor. For those with RA, understanding these potential connections and managing known flare triggers, including stress and sleep, are crucial for maintaining control of their condition. It is vital to consult with a healthcare provider or rheumatologist to discuss any concerns about medication and to ensure that prescribed antibiotics are used appropriately to treat infections while managing RA effectively. The ongoing research in this area continues to provide valuable insights into the intricate interplay between infections, the microbiome, and autoimmune disease activity. For reliable information on managing your condition, consult with an expert, such as those at the Johns Hopkins Arthritis Center.

Frequently Asked Questions

Not necessarily. While some observational studies have found general associations between antibiotic use and RA flare risk, a direct link is not confirmed. Research suggests the risk may vary depending on the specific antibiotic, with sulfonamide and trimethoprim showing a more notable association in one study.

The primary hypothesis is that antibiotics cause dysbiosis, or an imbalance, in the gut microbiome. This disruption can affect the immune system, leading to increased inflammation and potentially triggering an RA flare.

This is a key challenge for researchers, as the infection itself is a powerful immune system activator and a known trigger for RA flares. It is often difficult to definitively separate whether the flare is caused by the infection, the antibiotic, or a combination of both.

A 2019 study in Nature specifically associated sulfonamide and trimethoprim antibiotics with an increased risk of RA flares in the months following treatment. More research is needed to fully understand the effects of other antibiotic classes.

You should follow your doctor's instructions for the full course of antibiotics to properly treat the infection. However, you should also discuss your concerns with your rheumatologist, who can help monitor your symptoms and manage any potential flares.

Interestingly, some older antibiotics like minocycline have anti-inflammatory properties and were historically used as a treatment for RA. This illustrates the complex and varied effects that different antibiotic classes can have.

Focus on managing other known flare triggers like stress and sleep. Communicate with your rheumatologist about any concerns or changes in symptoms. Maintaining a healthy diet rich in anti-inflammatory foods can also support your gut health during and after antibiotic treatment.

Some studies have found that the effects on the gut microbiome can last up to a year, and the elevated risk of flare with specific antibiotics like sulfonamide and trimethoprim was observed for up to 12 months.