The Gut Truth About How Your Microbiome Affects Your Depression

Antibiotics show that the microbiome matters. Finding a cure might be harder.

This article is part of a Wise & Well Special Report: The United States of Depression.

Our gut microbiome, the trillions of diverse bacteria that live inside our small and large intestine, is innately connected to our brain. These bacteria don’t just feed on the food we eat; they produce a wide range of hormones and signals that affect health and behavior.

The food we choose to eat helps shape our microbiome. The right diet might offer a protective effect against depression. Conversely, when we take antibiotics, we sometimes see depression as a side effect, illustrating the power of the gut-mind connection. When we take an antibiotic, we temporarily kill the vast majority of our gut microbiome. Antibiotics kill all bacteria, friend and foe alike.

We can’t give up antibiotics; they’ve saved billions of lives. But to provide a better solution, we need to understand how the right gut microbiome, with the right diet, prevents depression in the first place.

Part of the problem is that most studies simply aren’t looking with enough detail to find that answer.

How to take a microbiome’s census

When scientists consider a possible link between two different systems or events (like microbiome vs. depression, or antibiotics vs. depression), they start by looking for a correlation. When we change one side of the equation, does the other side also change?

For the gut microbiome, the answer is yes. Significantly damage a person’s microbiome with antibiotics, and they are more likely to become depressed. But microbiomes aren’t simple to measure, leading to…

Question №1: Which specific bacteria cause, or prevent, depression?

Like fingerprints, each person has a unique gut microbiome. The staggering 100 trillion total bacteria are a blend of anywhere from 200 to 1,000 different species, depending on the individual, each with its own diet preferences and effects on its host.

Scientists can’t possibly identify every single one of a billion bacteria in a microbiome sample. Instead, they commonly use a technique called 16S sequencing, where they look at a couple regions of a single gene from each bacterium. It’s like looking at a blurry, low-resolution aerial photo: You can easily tell a forest from an ocean, but you can’t tell which species of trees are present.

This works great for showing general correlation. Aerial photos can tell us if an ocean is shrinking, and 16S sequencing can tell us if an overall microbiome has changed. But a blurry, low-resolution photo can’t tell us exactly which species of plants are in the picture, and 16S sequencing can’t tell us exactly which bacteria are taking over in depressed patients.

We need to use deeper, higher-resolution methods to look at the gut microbiome, identifying bacteria all the way down to their specific species and strain. But these methods are more expensive — and create thousands of times more data to sort through.

And that’s only the first step.

Killing both good bugs and bad ones

Antibiotics are like carpet bombs going off in the gut. They are designed to kill any bacteria they encounter, and they take down both disease-causing and happily co-existing bacteria alike. They don’t leave our gut entirely sterile, but they can kill about 90% of the bacteria living there.

That’s when some serious change happens.

Just as weeds pop up in a patch of bare dirt, new bacteria quickly move in on the freshly opened territory. Our gut quickly fills back up, but usually not with the same bacteria that were present previously. Imagine clear-cutting an ancient forest. New trees will spring up, but the first batch of trees will be small, fast-growing species instead of the larger, slower-growing trees that eventually overtake and replace them — maybe.

This leads to Question №2:

How do we kill disease-causing bacteria without also destroying our gut microbiome?

One approach might be to focus on the right bacteria returning through healthy food choices. Certain diets, like the Mediterranean diet with its heart-healthy olive oil, fish, whole grains, and beans, will bring out healthier microbiomes in the general population, but it may take weeks on this diet before the gut microbiome normalizes.

Another possibility is with a new class of antibiotics called narrow-spectrum antibiotics. Unlike the traditional broad-spectrum antibiotics, which kill all bacteria, narrow-spectrum antibiotics are designed to only kill specific groups of bacteria.

Narrow-spectrum antibiotics require more work to identify, but they may also help prevent the growing wave of bacteria with resistance to many broad-spectrum antibiotics.

Treat the microbiome, treat the depression

The correlation between microbiome disruption and depression raises a fascinating Question №3:

Can we use the microbiome to test for risk of depression? Could we encourage the right microbiome to prevent depression from appearing at all?

The short answer: not today, but maybe in the future.

Eating the right diet will keep our microbiome healthy, protecting against depression. But researchers still need to identify which bacteria, or groups of bacteria, or reliant-upon-each-other-entire-food-chains of bacteria, specifically promote mental stability. Scientists know which general groups of bacteria are “good,” but that’s still a bit like saying “forests are better than deserts.”

Additionally, researchers will need to find narrow-spectrum antibiotics that leave these groups happy and healthy, after they’ve been identified. That’s a process that will take years; it can take over a decade to validate a new antibiotic.

Finally, although the loss of a stable microbiome can cause depression, research hasn’t confirmed the opposite is true. Some limited evidence suggests that probiotics may help prevent depression, but the studies vary in the probiotic strains used, their length, and what they measured. It will take much stronger results before companies feel confident enough behind probiotics to put them through clinical trials as a method to prevent depression.

Probiotics may immunize us against depression… someday

Microbiome research needs to progress beyond overly broad 16S sequencing and focus on more specific sequencing methods to start identifying the specific bacteria that might offer a protective effect against depression. Scientists have made huge breakthroughs in proving a link exists, but there’s years more work to go before we see a specific treatment.

These days, even though commercial probiotics are widely available, they probably aren’t worth adding to your diet. They have little quality control and are often entirely mislabeled. A better choice is to focus on improving your overall diet, especially in regards to adequate fiber intake and a focus on whole grains, nuts, seeds, and small portions of fish and seafood, and getting enough sleep.

We shouldn’t avoid antibiotics, but we need to make sure we only use them at the right times. Remember, antibiotics only kill bacteria; they don’t provide any benefit against viruses, like COVID-19 or the flu. You should always feel empowered to speak with your healthcare provider about whether an antibiotic is necessary, especially if you have pre-existing depression.

Depression is complex, with many causes; it might be comforting to know that maintaining a positive outlook is not all in your head.

Sometimes, it’s in your gut as well.

This article is part of a Wise & Well Special Report: The United States of Depression. If you or a loved one is depressed, it’s vital to talk about it. Because depression increases the risk of suicide, consider calling the confidential National Suicide Prevention Lifeline at 1–800–273-TALK (8255) for English, 1–888–628–9454 for Spanish, or call or text 988. Global support in 44 languages is available from Befrienders Worldwide.