Antibiotics and the Brain, Part 1
It's complicated: Antibiotics can both cause and cure psychosis.
“Vaccines and antibiotics have made many infectious diseases a thing of the past; we've come to expect that public health and modern science can conquer all microbes. But nature is a formidable adversary.” — Tom Frieden
Antibiotics are a bona-fide medical miracle. When it comes to bacterial infections, nothing compares. Antibiotics have saved millions of lives. Got a cut? Antibiotics. Got strep throat? Antibiotics. Got a cold? Antibiotics. I threw in the last one to see if you are paying attention. Colds are caused by viruses, not bacteria, and antibiotics won’t help even a tiny bit. But so what? Better safe than sorry, right?
The dark side of antibiotics
Antibiotics have a dark side, and you should be aware of it. Scientists have long known about a direct connection between acute psychosis and certain antibiotics, including penicillin, fluoroquinolones, cephalosporins, and macrolides.
It can be tricky to show causality: The reason that antibiotics are administered is because of infection or inflammation, which can also lead to psychosis. How can we be sure antibiotics are to blame? Notably, causality has been pretty well established in cases where the psychosis was lifted when the antibiotics were stopped and returned when the antibiotics were resumed.
This isn’t a new finding; doctors have documented a wide variety of mental complications with penicillin since 1945. The list of symptoms is long, including seizures, aphasia, spasms, psychosis, confusion, lethargy, anxiety, and coma. These are serious side effects!
How can antibiotics affect behavior?
It’s not just penicillin: The documented psychiatric side effects of antibiotics other than penicillin range from mild symptoms to severe delirium and psychosis. It’s not an insignificant effect. For some antibiotics, up to 10% of users experience adverse neurologic effects.
Most of us take antibiotics orally, so what could possibly be happening in the gut to influence our moods and personalities? What is this weird connection between antibiotics and the brain? The prime suspect is the gut microbiota—the batch of microbes that live in our gut and help us with digestion and defense against pathogens.
Oral antibiotics can seriously damage the microbiota. That is, after all, the whole point of antibiotics: killing bacteria. Studies have shown that your microbiota can affect your brain via the gut-brain axis. Antibiotics disturb that axis by killing bacteria that produce neurotransmitters like GABA, dopamine, and serotonin. That disruption can affect your cognition and your mood. The good news here is that when the antibiotics are discontinued, the mental issues typically resolve quickly.
Challenges to the microbiota can be particularly impactful on children. In our first 1,000 days of childhood, our microbes are growing and changing as fast as we are. There’s a special vulnerability in this period. That’s when our immune system lets its guard down, learning to tolerate our beneficial bacteria. Although the details are still murky, the job must get done, or we will forever be fighting our homegrown microbes, setting us up for long-term inflammation.
Getting it right is important for more than just our gut: A proper microbiota helps the brain to develop normally as well. Giving antibiotics during this accommodation period risks killing the bacteria we need for healthy brain growth, affecting behavior. In mice, a lack of bacteria can cause an abnormal stress reaction. Providing those mice with a healthy microbiota puts them back on track, but only if they are younger than three weeks. After that, their stress response can’t recover.
Humans are not mice, but infants who take antibiotics have a less diverse microbiota and are more likely to get IBD and depression as adults. If your child really needs them, don’t hold back, but keep in mind that there might be long-lasting consequences.
Not all antibiotics are bad for the brain
In 1882, Robert Koch discovered that tuberculosis was caused by bacteria, and soon sanatoriums were established to deal with contagious patients. People with TB are often depressed, and sanatoriums are typically quiet, somber places.
In 1951, researchers decided to trial a new antibiotic, called isoniazid, to treat TB bacteria. To their surprise, the patients reacted weirdly: They started laughing and dancing in the hallways. The staff found themselves shushing their normally reserved patients. The researchers realized that, by pure serendipity, they had discovered the world’s first antidepressant drug.
They found that isoniazid prevented the breakdown of neurotransmitters, including serotonin, dopamine, and epinephrine. The race was on to find new drugs that could affect neurotransmitters. That focus ultimately led to all the modern antidepressants, including Prozac, Wellbutrin, Zoloft, and others.
Virtually forgotten in all the hoopla: isoniazid is an antibiotic. As well as lifting mood, the drug alters the microbiota. This was an early glimpse at the connection between microbes and brain function, but it was swiftly forgotten.
Another win for antibiotics is hepatic encephalopathy, a liver problem that affects the brain. It can cause anxiety and profound personality changes. It is not new: Hippocrates made a note of patients with liver disease and bad tempers. He said, “Those who are mad on account of bile are vociferous, vicious, and do not keep quiet.”
The culprit is ammonia, which causes edema in the brain. If untreated, it can lead to coma and death. Ammonia is a product of certain gut bacteria. One treatment is lactulose, a sugar that is consumed by lactobacillus bacteria, which multiplies and produces lactic acid. That increased acidity kills off many of those ammonia producers. In essence, lactulose feeds the enemy of our enemy. The ability to treat psychosis with antibiotics is a surprising illustration of the impact our gut bacteria have on our brains.
Next week, we’ll look at how you can make antibiotic treatments work better, and what the latest research has in store for the future.
References
Maier, Lisa, Camille V. Goemans, Jakob Wirbel, Michael Kuhn, Claudia Eberl, Mihaela Pruteanu, Patrick Müller, et al. “Unravelling the Collateral Damage of Antibiotics on Gut Bacteria.” Nature 599, no. 7883 (November 2021): 120–24.
Essali, Norah, and Brian J. Miller. “Psychosis as an Adverse Effect of Antibiotics.” Brain, Behavior, & Immunity - Health 9 (December 2020): 100148.
Mostafa, Safinaz, and Brian J. Miller. “Antibiotic-Associated Psychosis During Treatment of Urinary Tract Infections: A Systematic Review.” Journal of Clinical Psychopharmacology 34, no. 4 (August 2014): 483.
Yousafzai, Zaland A, Qazi Kamran Amin, Wajeeha Qayyum, Azhar Saeed, and Nouman Anthony. “Ciprofloxacin-Induced Acute Delirium in a Young Female.” Cureus 14, no. 5 (n.d.): e25182.
Mohsen, Samiha, James A. Dickinson, and Ranjani Somayaji. “Update on the Adverse Effects of Antimicrobial Therapies in Community Practice.” Canadian Family Physician 66, no. 9 (September 2020): 651–59.
Angela, it's weirder than you might think! Part 2 will deal with this, but check this out:
https://pubmed.ncbi.nlm.nih.gov/30193113/
Just had a week of a broad spectrum antibiotic. Now having a broad spectrum probiotics. I guess eating fibrous foods, prebiotics, kerfir will rectify my gut microbiome??!!