Your body has special cells called macrophages that act like tiny garbage trucks, cleaning up harmful bacteria in your lungs. Scientists discovered that when people lack a specific protein called ZIP8, these cleanup cells don’t work properly, making pneumonia infections worse. The good news? A supplement called phenylbutyrate appears to help these cells work better again, even when the ZIP8 protein is missing. This discovery could help billions of people worldwide who don’t get enough zinc in their diet, which is needed to make ZIP8 work correctly.

The Quick Take

  • What they studied: How a missing protein called ZIP8 makes it harder for immune cells to fight lung infections, and whether a supplement called phenylbutyrate could fix this problem
  • Who participated: Laboratory mice that were genetically modified to lack the ZIP8 protein, plus their normal immune cells grown in dishes
  • Key finding: Mice without ZIP8 got much sicker from pneumonia because their immune cells couldn’t properly destroy bacteria. However, when given phenylbutyrate supplement, these mice recovered better and had fewer bacteria in their lungs
  • What it means for you: If you have low zinc levels or carry a genetic variant affecting ZIP8, phenylbutyrate supplementation might help your body fight lung infections better. However, this is early research in mice, and more studies in humans are needed before doctors would recommend this treatment

The Research Details

Scientists created mice that couldn’t make the ZIP8 protein, which normally helps immune cells absorb zinc. They infected these mice with pneumonia bacteria and watched what happened to their immune system. They also studied immune cells in laboratory dishes to understand exactly how ZIP8 works. Finally, they tested whether giving the mice phenylbutyrate (a supplement that helps gut bacteria make helpful compounds) would improve their immune response.

The researchers examined the macrophages—the immune cells that eat and destroy bacteria—under microscopes and tested their ability to kill bacteria. They looked at specific structures inside these cells called lysosomes, which are like tiny bags of cleaning chemicals that break down bacteria.

Understanding how zinc deficiency weakens immune defenses is important because billions of people worldwide don’t get enough zinc. This research shows that the problem isn’t just about having less zinc—it’s about a specific protein that can’t do its job without zinc. Finding that a supplement can partially fix this problem offers hope for a practical treatment that doesn’t require fixing the genetic issue itself.

This is laboratory research using mice and cells in dishes, which is an important first step but doesn’t prove the same thing happens in humans. The study was published in a peer-reviewed scientific journal, meaning other experts checked the work. However, because it’s animal research, results may not directly apply to people. The researchers were transparent about what they found and what still needs investigation.

What the Results Show

Mice without the ZIP8 protein got much sicker when infected with pneumonia bacteria. Even though their bodies sent more immune cells to fight the infection, these cells couldn’t do their job properly. The immune cells had fewer and smaller lysosomes—the structures that contain bacteria-killing chemicals—so bacteria piled up inside the cells instead of being destroyed.

When researchers gave these mice phenylbutyrate supplement, something remarkable happened: the immune cells started working better. The supplement helped restore the ability of these cells to kill bacteria, and the mice recovered from infection more successfully. This worked even though the mice still lacked the ZIP8 protein.

The researchers discovered that ZIP8 normally helps control a specific pathway inside cells (called mTORC1/TFEB) that tells cells to make more lysosomes. Without ZIP8, this pathway doesn’t work right. Phenylbutyrate appears to activate this pathway through a different route, bypassing the need for ZIP8.

The study showed that zinc deficiency affects not just the amount of immune cells your body makes, but also how well those cells function. The researchers also found that ZIP8 affects how gut bacteria produce helpful compounds called butyrate. This suggests that zinc deficiency creates multiple problems in the body’s defense system, not just one.

Previous research showed that zinc deficiency increases pneumonia risk worldwide. This study explains one of the reasons why: it’s not just that people have fewer immune cells, but that the cells they do have don’t work properly. The finding that phenylbutyrate can help is novel and suggests a new treatment approach that hasn’t been widely explored before.

This research was done in mice and laboratory cells, not in humans, so we can’t be sure the same effects would occur in people. The study didn’t test phenylbutyrate in humans or compare it to other possible treatments. We don’t know the right dose for humans or whether long-term use would be safe. Additionally, the research focused on one specific type of pneumonia bacteria, so results might differ with other infections.

The Bottom Line

Based on this research alone, phenylbutyrate supplementation is NOT recommended for general use yet. This is early-stage research that needs to be tested in humans first. However, if you have zinc deficiency or recurrent lung infections, talk to your doctor about whether zinc supplementation or other treatments might help. The research suggests that maintaining adequate zinc intake through diet (meat, nuts, seeds, legumes) is important for immune function.

This research is most relevant to people with zinc deficiency, those with genetic variants affecting ZIP8, and people with recurrent pneumonia infections. It’s also important for public health experts considering how to address zinc deficiency in developing countries. People with normal zinc levels and no genetic risk factors may not see benefits from phenylbutyrate supplementation.

If phenylbutyrate were eventually approved for human use, benefits would likely take weeks to months to appear, as the immune system needs time to rebuild its defenses. This isn’t a quick fix but rather a way to help the body’s natural defense systems work better.

Want to Apply This Research?

  • Track zinc intake from food sources daily (target: 8-11 mg for adults) and monitor any respiratory infections or symptoms like cough, fever, or shortness of breath. Note frequency and severity of infections over 3-month periods.
  • Increase dietary zinc by adding more zinc-rich foods: beef, chicken, oysters, cashews, chickpeas, and pumpkin seeds. If considering any supplementation, consult your doctor first and track any changes in infection frequency or respiratory health.
  • Maintain a 6-month log of respiratory infections, their severity, and recovery time. Also track dietary zinc intake and any supplements taken. Share this data with your healthcare provider to identify patterns and assess whether dietary changes are helping your immune function.

This research is preliminary laboratory work in mice and has not been tested in humans. Do not start phenylbutyrate supplementation or change your zinc intake without consulting your healthcare provider. This article is for educational purposes only and should not replace professional medical advice. If you have recurrent infections or suspect zinc deficiency, speak with your doctor about appropriate testing and treatment options. Always consult a healthcare professional before starting any new supplement or making significant dietary changes.