Antibiotics in Foods

Widespread, decade use of antibiotics in both livestock husbandry and human healthcare has led to trace amounts of these drugs and their byproducts ending up in everyone's food. 

The problem we face is one of unintentional and multifaceted exposure. Long-term consumption of antibiotics causes several health problems; it's been quite challenging scientifically to analyze more than a few antibiotics at a time. This is because the hundreds of antibiotics on the market ALL have different chemical properties. The majority of past monitoring methods for antibiotics in foods have been limited to a few compounds at a time, usually within a single class of antibiotics with similar structures and chemical properties.  

So, if you are looking for an antibiotic in a certain food (where it shouldn’t be), and the one “chemical shape” is not found, then that means many more could have been present—they were just missed because you were only looking for one chemical shape! Just because one antibiotic residue was not found does not mean the food is “antibiotic-free” as consumers are often fooled to believe when purchasing their animal products at any food dispensary; it simply means the food was free from the ONE class of antibiotics analyzed. Fortunately, researchers reporting in the Journal of Agricultural and Food Chemistry have developed a method to simultaneously measure 77 common antibiotics in a variety of foods. This is a huge step forward in casting a wider net, and certainly better than looking for just one or two antibiotics at a time. More on this in a bit … 

Typically, antibiotics are found in trace amounts in animal products like meat, eggs, and milk if the animals are not withdrawn from the drugs for a sufficient period of time before the animal (or its products) are gathered and processed. Unfortunately, most animals are kept on antibiotics their entire life to ensure farmers net a profit. 

The main concern we have about consuming foods with antibiotic residues (beyond the imbalances that occur in the gut microbiome) is that it could lead to increased antibiotic resistance of bacterial pathogens. This, of course, is the exact same concern we have about long-term antibiotic prescriptions. In other words, long-term exposure to large and small doses (via prescription antibiotics or from common foods) could set the stage for a disastrous outcome as it veers from the initial set point. 

Today, we can detect a wider range of antibiotics in a wider range of foods than before, and it can be done in a time- and cost-effective manner. After establishing that their method was sensitive and accurate with spiked antibiotics in several foods, researchers recently applied it to store-bought samples of wheat flour, lamb, eggs, milk, cabbage, and bananas, and detected a total of 10 antibiotics. One of them, roxithromycin, was detected at trace amounts in all six food types. This new method is just beginning to be used in research studies, and it will help with our understanding, monitoring, and regulating antibiotic levels in foods.

What We Know:  Asthma, Allergic Diseases, and Autoimmunity

Antibiotics are particularly potent at causing seismic change in the body because of their direct effect on the microbiome. Even transient alterations during critical developmental periods in early life can compromise both immune tolerance and inflammatory responses (Gensollen et al., 2016).

We know that children with immature intestinal microbiota and low abundance of specific bacterial taxa are at increased risk for asthma (Arrieta et al., 2015; Stokholm et al., 2018).

Antibiotic exposure at any point in a child’s life is associated with food allergy risk -- this is profound for a nation whose children are battling rising food allergy epidemic with “no known cause”. If antibiotics are administered to the mother during pregnancy, childbirth and/or during the first few years of a child’s life along with any exposure to cow’s milk and/or eggs (both directly and through breastmilk and formula), the risk of developing food allergies is extremely common. The risk is worsened if the child was given any anti-acid/colic medications which prevent the production of hydrochloric acid in the stomach (Mitre et al., 2018).

With less acid available, the stomach is no longer able to easily digest food and absorb critical nutrients and vitamins. It also leads to proliferation of pathogenic bacteria no longer killed off by stomach acid.  As more undigested “toxic” food particles reach the intestines putrefying in the colon, the gut’s microbiome begins to suffer dire consequences. Our health now hangs in jeopardy. 

This rightfully begs the question, do all drugs impact the microbiome? Until proven beyond a shadow of a doubt, most drugs that pass the GI tract likely change some aspect of it, yes. I would argue that all drugs likely impact the microbiome on a spectrum of least damaging to most damaging. At the very least, drugs like antacids and antibiotics cause massive damage to the gut’s microbiome during vital developmental periods (Gensollen et al., 2016; Blaser, 2017) known to subsequently cause a panacea of autoimmune diseases. For instance, the risk of celiac disease, inflammatory bowel disease, autism, ADHD and other learning disorders is dramatically increased if a child receives even one or more antibiotic prescriptions (specifically penicillins and cephalosporins) in their first 2 years of life. 

What We Know:  Obesity & Cognitive Function

How does pumping animals up with antibiotics fattens them up? -- while this question deserves its own blog, the answer lies within the animal’s microbiome. Fed antibiotics from day 1 of birth, animal’s most pathogenic bacteria quickly proliferate inside the gut. For example, when Clostridium difficile overgrows and causes an infection, the animal is no longer able to easily access energy from food consumed. This ‘unused food’ fattens them, but also accelerates them becoming diseased. 

This same effect happens in children -- when they are exposed to antibiotics in early life and/or fed any animal products (i.e, casein/whey in formula or via breastmilk), their gut bacteria quickly becomes imbalanced. The pathogenic bacteria begin hijacking critical nutrients from the beneficial bacteria and overgrowing. The digestive system is unable to easily extract nutrients and vitamins from food consumed leaving cells starving.  The child quickly begins gaining excess weight as a form of survival leading to our nation’s childhood obesity epidemic. 

Childhood is a critical window when the microbiome becomes established fully by age 3 to 5. The greater the diversity of microorganisms sets the stage for health years down the road. The lack of diversity in youth sets the stage for illness to encroach decades sooner than would be expected (which is exactly what we’re seeing in clinics now). For instance, when the gut microbiome becomes disrupted early in a child’s development, it sets them up for a whole host of neurological and behavioral disorders. 

We are still learning what constitutes a healthy microbiome: its richness, interaction with other microbes, viruses, fungi, and the like. What’s likely missing from all of these research studies is the personalization needed to correct the underlying imbalances. For some it’s diet, for others it’s stress; for some it’s immune tolerance, and for others it’s a combination of all three approaches for which no single treatment alone will suffice.

The key to optimizing patient outcomes in real time is 100% dictated by delivering personalized care through advanced diagnostics and treatment options. Without this framework, it’s like we are going to continue to take more steps back than forward in the overall course trajectory of a patient’s life quality and quantity.

For instance, two recent studies didn’t find an association between antibiotic exposure and autism (Hamad et al., 2018; Axelsson et al., 2019b), but they did not discern between antibiotic classes, which means all of them were lumped together with no stratification which basically makes the results of these studies invalid for drawing any useful conclusions.

By contrast, another recent study found an association between any treated infection and several childhood and adolescent neurobehavioral conditions; for autism, the risk was significantly increased only in kids who needed hospitalization for their infection (Köhler-Forsberg et al., 2019).

In Conclusion

Antibiotics are ubiquitous, and exposure in the first 2 years of life is associated with an increased risk of several health concerns in children, but there’s a lot you can do to build the best microbiome and limit your risk of developing major health concerns in the short and long term. Stay tuned for more information this fall

References

Aarts, E., Ederveen, T. H., Naaijen, J., Zwiers, M. P., Boekhorst, J., Timmerman, H. M., ... & Arias Vasquez, A. (2017). Gut microbiome in ADHD and its relation to neural reward anticipation. PloS one, 12(9), e0183509.

Arrieta, M. C., Stiemsma, L. T., Dimitriu, P. A., Thorson, L., Russell, S., Yurist-Doutsch, S., ... & CHILD Study Investigators. (2015). Early infancy microbial and metabolic alterations affect risk of childhood asthma. Science translational medicine, 7(307), 307ra152-307ra152.

Aversa, Z., Atkinson, E. J., Schafer, M. J., Theiler, R. N., Rocca, W. A., Blaser, M. J., & LeBrasseur, N. K. (2021, January). Association of infant antibiotic exposure with childhood health outcomes. In Mayo Clinic Proceedings (Vol. 96, No. 1, pp. 66-77). Elsevier.

Axelsson, P. B., Clausen, T. D., Petersen, A. H., Hageman, I., Pinborg, A., Kessing, L. V., ... & Løkkegaard, E. C. L. (2019a). Investigating the effects of cesarean delivery and antibiotic use in early childhood on risk of later attention deficit hyperactivity disorder. Journal of Child Psychology and Psychiatry, 60(2), 151-159.

Axelsson, P. B., Clausen, T. D., Petersen, A. H., Hageman, I., Pinborg, A., Kessing, L. V., ... & Løkkegaard, E. C. L. (2019b). Relation between infant microbiota and autism?: results from a national cohort sibling design study. Epidemiology, 30(1), 52-60.

Azad, M. B., Bridgman, S. L., Becker, A. B., & Kozyrskyj, A. L. (2014). Infant antibiotic exposure and the development of childhood overweight and central adiposity. International journal of obesity, 38(10), 1290-1298.

Bailey, L. C., Forrest, C. B., Zhang, P., Richards, T. M., Livshits, A., & DeRusso, P. A. (2014). Association of antibiotics in infancy with early childhood obesity. JAMA pediatrics, 168(11), 1063-1069.

Blaser, M. J. (2017). The theory of disappearing microbiota and the epidemics of chronic diseases. Nature Reviews Immunology, 17(8), 461-463.

Cho, I., Yamanishi, S., Cox, L., Methé, B. A., Zavadil, J., Li, K., ... & Blaser, M. J. (2012). Antibiotics in early life alter the murine colonic microbiome and adiposity. Nature, 488(7413), 621-626.

Cox, L. M., Yamanishi, S., Sohn, J., Alekseyenko, A. V., Leung, J. M., Cho, I., ... & Blaser, M. J. (2014). Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cell, 158(4), 705-721.

Dinan, T. G., Stilling, R. M., Stanton, C., & Cryan, J. F. (2015). Collective unconscious: how gut microbes shape human behavior. Journal of psychiatric research, 63, 1-9.

Gensollen, T., Iyer, S. S., Kasper, D. L., & Blumberg, R. S. (2016). How colonization by microbiota in early life shapes the immune system. Science, 352(6285), 539-544.

Hamad, A. F., Alessi-Severini, S., Mahmud, S. M., Brownell, M., & Kuo, I. F. (2018). Early childhood antibiotics use and autism spectrum disorders: a population-based cohort study. International journal of epidemiology, 47(5), 1497-1506.

Hirsch, A. G., Pollak, J., Glass, T. A., Poulsen, M. N., Bailey‐Davis, L., Mowery, J., & Schwartz, B. S. (2017). Early‐life antibiotic use and subsequent diagnosis of food allergy and allergic diseases. Clinical & Experimental Allergy, 47(2), 236-244.

Hoskin‐Parr, L., Teyhan, A., Blocker, A., & Henderson, A. J. W. (2013). Antibiotic exposure in the first two years of life and development of asthma and other allergic diseases by 7.5 yr: a dose‐dependent relationship. Pediatric Allergy and Immunology, 24(8), 762-771.

Hu, M., Ben, Y., Wong, M. H., & Zheng, C. (2021). Trace Analysis of Multiclass Antibiotics in Food Products by Liquid Chromatography-Tandem Mass Spectrometry: Method Development. Journal of Agricultural and Food Chemistry, 69(5), 1656-1666.

Köhler-Forsberg, O., Petersen, L., Gasse, C., Mortensen, P. B., Dalsgaard, S., Yolken, R. H., ... & Benros, M. E. (2019). A nationwide study in Denmark of the association between treated infections and the subsequent risk of treated mental disorders in children and adolescents. JAMA psychiatry, 76(3), 271-279.

Kozyrskyj, A. L., Ernst, P., & Becker, A. B. (2007). Increased risk of childhood asthma from antibiotic use in early life. Chest, 131(6), 1753-1759.

Leffler, D. A., & Lamont, J. T. (2015). Clostridium difficile infection. New England Journal of Medicine, 372(16), 1539-1548.

Metsälä, J., Lundqvist, A., Virta, L. J., Kaila, M., Gissler, M., & Virtanen, S. M. (2013). Mother's and offspring's use of antibiotics and infant allergy to cow's milk. Epidemiology, 303-309.

Mitre, E., Susi, A., Kropp, L. E., Schwartz, D. J., Gorman, G. H., & Nylund, C. M. (2018). Association between use of acid-suppressive medications and antibiotics during infancy and allergic diseases in early childhood. JAMA pediatrics, 172(6), e180315-e180315.

Schroeder, B. O., & Bäckhed, F. (2016). Signals from the gut microbiota to distant organs in physiology and disease. Nature medicine, 22(10), 1079.

Scott, F. I., Horton, D. B., Mamtani, R., Haynes, K., Goldberg, D. S., Lee, D. Y., & Lewis, J. D. (2016). Administration of antibiotics to children before age 2 years increases risk for childhood obesity. Gastroenterology, 151(1), 120-129.

Stark, C. M., Susi, A., Emerick, J., & Nylund, C. M. (2019). Antibiotic and acid-suppression medications during early childhood are associated with obesity. Gut, 68(1), 62-69.

Stokholm, J., Blaser, M. J., Thorsen, J., Rasmussen, M. A., Waage, J., Vinding, R. K., ... & Bisgaard, H. (2018). Maturation of the gut microbiome and risk of asthma in childhood. Nature communications, 9(1), 1-10.

Vuong, H. E., Yano, J. M., Fung, T. C., & Hsiao, E. Y. (2017). The microbiome and host behavior. Annual review of neuroscience, 40, 21-49.

Author

Dr. Payal Bhandari M.D. is one of U.S.'s top leading integrative functional medical physicians and the founder of SF Advanced Health. She combines the best in Eastern and Western Medicine to understand the root causes of diseases and provide patients with personalized treatment plans that quickly deliver effective results. Dr. Bhandari specializes in cell function to understand how the whole body works. Dr. Bhandari received her Bachelor of Arts degree in biology in 1997 and Doctor of Medicine degree in 2001 from West Virginia University. She the completed her Family Medicine residency in 2004 from the University of Massachusetts and joined a family medicine practice in 2005 which was eventually nationally recognized as San Francisco’s 1st patient-centered medical home. To learn more, go to www.sfadvancedhealth.com.