ACEND

Medications and the Microbiome: The Hidden Side Effects of Modern Medicine

Date: November 2025

Contributing Authors: Team TRILITY / ACEND

The human gut microbiome is a complex community of trillions of bacteria, fungi, and yeasts that profoundly influence human health. It supports digestion, nutrient absorption, metabolism, immune regulation, and even brain function. Yet new research reveals that many common medications—well beyond antibiotics—can leave a lasting imprint on this delicate ecosystem, sometimes for years after use.

When Medicine Meets Microbes

For decades, antibiotics were known to alter gut bacteria, wiping out not only pathogens but also beneficial species that produce short-chain fatty acids (SCFAs) and maintain gut-barrier integrity. But a landmark 2025 study published in the American Society for Microbiology’s journal mSystems found that at least seven major classes of prescription drugs can also disrupt the microbiome long after discontinuation.

Researchers from the University of Tartu in Estonia analyzed stool samples from 2,509 adults in the Estonian Biobank. Using shotgun metagenomic sequencing and prescription records, they assessed the microbial impact of 186 medications—and discovered that 167 altered the microbiome in measurable ways, while 78 produced long-term effects persisting even after use stopped.

“Even within the same class of drugs, individual medications can affect the microbiome in very different ways,” explained Dr. Elin Org, head of the Microbiome Research Group at the University of Tartu. “If two drugs work equally well, doctors may opt for the one that has a smaller impact on the gut microbiome.”

Seven Medication Classes That Disrupt the Microbiome

  1. Antibiotics – Kill pathogenic bacteria but also destroy beneficial species, reducing microbial diversity and SCFA production.

  2. Antidepressants – Affect gut motility and serotonin signaling, reshaping microbial populations linked to mood regulation.

  3. Antipsychotics – Modify bacterial gene expression and metabolism, possibly contributing to weight gain and metabolic changes.

  4. Beta-blockers – Influence intestinal motility and bile acid metabolism, indirectly changing microbial balance.

  5. Biguanides (Metformin) – Paradoxically, this diabetes drug can improve glucose control partly by enriching beneficial bacteria like Akkermansia muciniphila.

  6. Proton Pump Inhibitors (PPIs) – Suppress gastric acid, allowing bacterial overgrowth in the small intestine and increasing infection risk.

  7. Benzodiazepines – Showed the strongest negative impact in the Estonian study. Alprazolam (Xanax) disrupted microbial composition far more than diazepam (Valium).

Dr. Babak Firoozi, gastroenterologist at MemorialCare Orange Coast Medical Center, noted:

“The most surprising finding is how many classes of drugs appeared to influence the gut biome. These effects can accumulate with long-term or multiple prescriptions.”

How Drugs Disrupt Gut Ecology

Medications can alter microbial communities through several mechanisms:

  • Changes in pH – PPIs reduce stomach acidity, allowing microbes to migrate and colonize new niches.

  • Altered Motility – Beta-blockers and benzodiazepines slow intestinal transit, giving certain bacteria more time to proliferate.

  • Direct Toxicity – Some drugs inhibit bacterial enzymes or metabolic pathways shared with human cells.

  • Indirect Effects – Appetite changes, dietary shifts, and immune modulation all reshape the gut’s internal ecosystem.

Over time, these changes may contribute to dysbiosis—a disrupted microbial state associated with inflammatory bowel disease (IBD), type 2 diabetes, obesity, autoimmune conditions, and cardiovascular disease.

Why This Matters for Long-Term Health

The gut microbiome helps regulate inflammation and immune balance. When it’s disturbed, inflammatory pathways such as NF-κB and IL-6 can become overactive, increasing oxidative stress and intestinal permeability (“leaky gut”).
This chronic low-grade inflammation links directly to many conditions ACEND targets, including metabolic dysfunction, brain fog, fatigue, and accelerated aging.

Because many medications are taken continuously rather than short-term—unlike most antibiotics—their microbiome impacts may be deeper and more persistent.

“Given that human-targeted drugs are often taken continuously throughout life, the physiological effects can be even more profound,” wrote the mSystems authors.

Supporting Your Microbiome While on Medication

It’s rarely possible—or wise—to discontinue necessary prescriptions. But you can help your microbiome remain resilient:

  • Feed beneficial bacteria. Prebiotic fibers like partially hydrolyzed guar gum (Sunfiber®) and gum acacianourish beneficial microbes that produce anti-inflammatory SCFAs.

  • Repopulate diversity. Probiotics such as Bacillus coagulans and Bifidobacterium longum support recolonization after antibiotic or PPI use.

  • Fortify with polyphenols. Compounds like curcumin, quercetin, rosmarinic acid, and EGCG help restore microbial diversity and suppress pro-inflammatory species.

  • Replenish key nutrients. Many medications deplete magnesium, zinc, and B-vitamins, which are essential for gut and mitochondrial health.

  • Consider medical foods. ACEND®, developed for the dietary management of chronic inflammation, integrates clinically validated polyphenols, prebiotics, and micronutrients to promote microbial resilience and whole-body balance.

The Future of Microbiome-Aware Medicine

As research deepens, personalized prescribing may soon include microbiome profiling—helping physicians choose drugs that treat disease while minimizing collateral microbial damage.
Understanding these interactions could redefine preventive care, linking pharmacology and nutrition in a single therapeutic ecosystem.

Therefore, we suggest

that protecting your microbiome should be considered part of any long-term medication strategy. By nourishing this internal community through food-based science, lifestyle balance, and targeted formulations like ACEND®, you can help your gut—and your whole body—thrive in harmony with modern medicine.

References

  1. Aasmets O. et al. A hidden confounder for microbiome studies: medications used years before sample collection.mSystems (2025).

  2. Maier L. et al. Extensive impact of non-antibiotic drugs on human gut bacteria. Nature (2018).

  3. Forslund K. et al. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota.Nature (2015).

  4. Jackson M.A. et al. Proton pump inhibitors alter the composition of the gut microbiota. Gut (2016).

  5. Cryan J.F. et al. The microbiota–gut–brain axis. Physiological Reviews (2019).

  6. Wallace J.L. et al. NSAIDs and intestinal damage: lessons from animal and human studies. Gastroenterology(2020).

Other articles you may enjoy

Note: Always consult with a healthcare professional before considering any treatment options or significant dietary changes.