Aspirin & the gut

One size fails all: the hidden dialogue between aspirin and microbiome

Aspirin and pediatric aspirin are among the most widely used medications worldwide. They are used for pain, inflammation, to prevent cardiovascular disease, and sometimes even for cancer prevention. But where one patient benefits, another is at risk for gastrointestinal complications.

So the question is not: is aspirin good or bad?
The right question is: for whom does it work, and for whom can it be harmful?

The answer lies in the crosstalk between DNA, microbiome and metabolites.

The problem

• NSAIDs (including aspirin) cause hundreds of thousands of hospitalizations each year due to gastrointestinal bleeding.
• Pediatric aspirin (low dose) is often considered "safe," but can cause subtle damage to the intestinal barrier in some people.
• "One size fits all" recommendations ignore genetic differences, microbial interactions and individual risk factors.

Multi-omics insights into aspirin & gut

1. DNA profiles
   - Variations in genes such as CYP2C9 and UGT1A6 affect aspirin degradation and increase the risk of side effects.
2. Microbiome interaction
   - Gut bacteria can metabolize aspirin, altering both efficacy and toxicity.
3. Barrier & mucosa
   - Aspirin can weaken the intestinal barrier, resulting in dysbiosis and microbial translocation.
4. Benefit-disadvantage balance.
   - Aspirin has been shown to protect some patients from myocardial infarction and colorectal cancer, but primarily increases the risk of GI bleeding in others.

What recent studies show

• Cancer prevention in Lynch syndrome
  The CAPP2 trial showed that daily use of 600 mg aspirin for ≥2 years reduced the risk of colorectal cancer by ~60% in people with Lynch syndrome (hereditary predisposition).
  Clear benefit for a specific genetic subgroup.
• No universal benefit in the elderly
  The ASPREE trial (Bakshi et al., 2022) found that in people over 70, aspirin did not significantly protect against colorectal cancer, even in those at high genetic risk.
  Age and context are determinants.
• Risk of bleeding
  The Nurses' Health Study (Huang et al., 2011) showed that the risk of GI bleeding increases primarily with dose, rather than duration of use.
  Low doses over long periods of time may be relatively safe, but higher doses greatly increase the risk.
• Low-dose aspirin not without risk
  A Danish cohort study (Sørensen et al., 2000) showed that even low-dose aspirin doubles to triples the risk of upper GI bleeding, especially in the elderly or those also taking other NSAIDs/anticoagulants. Age and context are determinants.
• Other risk factors
  Valkhoff et al. (2012) identified additional risks: older age, comorbidities, helicobacter infection and polypharmacy. Age and context are determinants.

Innovative solutions

1. Pharmaco-Crosstalk Index.
   - My InnerSelfie links DNA, microbiome and metabolites to predict who benefits from aspirin and who is at risk.
2. Barrier monitoring
   - Multi-omics detects subtle mucosal damage before symptoms develop.
3. Therapy personalization
   - Physicians can tailor dosage and timing of aspirin to patient profile, rather than generic recommendations.

Why My InnerSelfie is unique

• Multi-omics integration: DNA, microbiome and metabolites analyzed together.
• Crosstalk focus: visualizing how aspirin interacts with gut barrier and microbiome.
• Preventive precision: identify risks of complications early.
• Win-win: patients enjoy the benefits of aspirin, doctors and hospitals reduce complications.
• Tomorrow's care: innovative, preventive and always customized. Innovation of today becomes the standard of tomorrow - safe and scientifically based.

Key insights

• Aspirin is not a one size fits all: DNA, microbiome and age determine effectiveness and risk.
• In Lynch syndrome, there is clear benefit; not always in the elderly.
• Multi-omics reveals the difference between protection and complication.
• My InnerSelfie supports physicians in therapy selection and dosing.

Scientific references

• Serrano M, Burn J, Mathers JC, et al. CAPP2 trial: Aspirin reduces colorectal cancer in Lynch syndrome. Genes. 2022.
• Bakshi A, et al. Aspirin and colorectal cancer risk in older adults: ASPREE. PubMed. 2022.
• Huang ES, Strate LL, Ho WW, Lee SS, Chan AT. Long-term aspirin use and risk of GI bleeding. Gastroenterology. 2011.
• Sørensen HT, et al. Risk of upper gastrointestinal bleeding with low-dose aspirin. Arch Intern Med. 2000.
• Valkhoff VE, Sturkenboom MC, Kuipers EJ. Risk factors for GI bleeding in aspirin users. Gastroenterology. 2012.
• Caruso R, Lo BC, Núñez G. Host-microbiota interactions in inflammation. Nat Rev Immunol. 2020.