Since the discovery of penicillin by Alexander Fleming, the utility and efficacy of antibiotics in combating infectious diseases has been a game changer. Unfortunately, the overuse of antibiotics—especially when used inappropriately for viral infections—has led to numerous unintended consequences, limiting the benefits while increasing the likelihood of side effects.

 

Consequences of Inappropriate Antibiotic Use

The inappropriate use of antibiotics has led to the emergence of multiple drug-resistant bacteria, making this issue a pressing public health problem.1 This over-exposure to antibiotics also takes place in our food supply, as 80% of all antibiotics used in the United States are fed to farm animals to the tune of 160,000 tons in 2020.2

These antibiotics have been shown to disturb the composition and function of the gut microbiota, resulting in alterations to immunity, metabolism and health.3 

 

Mitochondria and Ancient Microbial Origins

Recent research has shed light on a lesser-known aspect of antibiotic use, particularly their impact on the vital cellular powerhouse, the mitochondria. Mitochondria are unique in that they have their own DNA (mtDNA) and are theorized by Dr. Lynn Margulis under the endosymbiotic theory to be an ancient form of bacteria that were taken into larger cells where they produced energy in exchange for protection from the elements.4

While mitochondria play a critical role in energy production and cellular regulation, they are also vulnerable to the effects of various antibiotics, which may lead to unforeseen health implications.

 

Disruption of the Microbiome and Mitochondria by Antibiotics

Prolonged antibiotic use, especially with broad-spectrum antibiotics, can disrupt the balance of the gut microbiota as well as mitochondrial function and energy metabolism.5 Certain classes of antibiotics, particularly fluoroquinolones and tetracyclines, can disrupt mitochondrial function, leading to oxidative stress and the subsequent generation of reactive oxygen species (ROS).

This oxidative stress can ultimately result in cellular damage and contribute to the development of various adverse effects, including an array of metabolic disorders, such as obesity, insulin resistance, neurodegenerative disorders and cardiovascular complications.5

 

Direct Mitochondrial Toxicity of Antibiotics

Mitochondrial toxicity induced by antibiotics serves as a critical reminder for health care practitioners to exercise caution and prudence when prescribing these medications. Antibiotic classes, such as macrolides and fluoroquinolones, have been shown to cause mitochondrial toxicity by targeting a variety of mitochondrial mechanisms and targets, including disrupting mtDNA.6

 

Antibiotics and Drug-Induced Nutrient Depletion

Antibiotics can also deplete essential micronutrients necessary for mitochondrial function. These nutrient depletions include folic acid, iron, calcium, magnesium, and vitamins B1, B2, B3, B5, B6, B12, A, D, and K.7

While fluoroquinolones cause calcium and iron de­ficiencies, tetracyclines can inhibit the absorption of vita­min B6, calcium, magnesium, iron and zinc in the gastro­intestinal tract when the nutrients bind to this type of drug.7 Moreover, trimethoprim causes folic acid deficiency; pen­icillin and cephalosporins cause B and K vitamin deficien­cies; and aminoglycosides, such as gentamicin, neomycin, and streptomycin, cause magnesium, calcium, and potas­sium imbalances and vitamin B and K deficiencies.7

 

Nutrient Support for Mitochondrial Function

When antibiotics are necessary, the potential risks may be mitigated by taking measures to support mitochondrial function. This may include supplying patients with micronutrients and antioxidants, such as the following:

  • N-acetyl cysteine
  • Alpha lipoic acid
  • Acetyl-L-carnitine

 A high-quality multivitamin may also reduce the risk of drug-induced nutrient depletion.

 

Beyond Bacteria: How Antibiotics Impact Mitochondria

 

 

Putting It All Together

The intricate relationship between antibiotics and mitochondria necessitates a comprehensive understanding of the potential implications for patient health. As health care practitioners, we must be vigilant and judicious in our approach to antibiotic administration, prioritizing a balance between eradicating infections and preserving the delicate equilibrium of our cellular powerhouses.

 

 

 

Head shot of Kareem Kandil, MD, ND

Kareem Kandil, MD, ND is the Immune Foundations Clinical Brand Manager at Lifestyle Matrix Resource Center. Upon graduating from medical school at Ross University School of Medicine, Dr. Kandil went on to do an observership in integrative medicine and then pursued his Doctorate of Naturopathic Medicine (ND) at National University of Health Sciences in Lombard, IL.

 

 

 

References
1. Habboush Y, Guzman N. Antibiotic Resistance. StatPearls Publishing. 2023 Jan. Online. https://www.ncbi.nlm.nih.gov/books/NBK513277/
2. Tons of antibiotics used for livestock. The World Counts; date unknown. Accessed November 11, 2023. https://www.theworldcounts.com/challenges/consumption/foods-and-beverages/antibiotics-used-for-livestock
3. Francino MP. Antibiotics and the Human Gut Microbiome: Dysbioses and Accumulation of Resistances. Front Microbiol. 2016 Jan 12;6:1543. doi: 10.3389/fmicb.2015.01543. 
4. Gray MW. Lynn Margulis and the endosymbiont hypothesis: 50 years later. Mol Biol Cell. 2017;28(10):1285-1287. doi:10.1091/mbc.E16-07-0509
5. Salimiaghdam N, Singh L, Schneider K, et al. Effects of fluoroquinolones and tetracyclines on mitochondria of human retinal MIO-M1 cells. Exp Eye Res. 2022 Jan;214:108857. doi: 10.1016/j.exer.2021.108857. 
6. Will Y, Shields JE, Wallace KB. Drug-Induced Mitochondrial Toxicity in the Geriatric Population: Challenges and Future Directions. Biology. 2019; 8(2):32. https://doi.org/10.3390/biology8020032
7. Yalçın N, Armut M, Kelleci Çakır B, Demirkan K. Drug-induced nutritional disorders. Clin Sci Nutr. 2020. 1(3): 113-22. doi: 10.5152/ClinSciNutr.2020.962