It is slowly changing. The largest analysis of depression and the gut microbiome to date, published in December, found that several types of bacteria increased or decreased significantly in people with symptoms of depression.
“This study provides concrete evidence that you are what you eat,” says study author Andre Uitterlinden, a genetics researcher at Erasmus Medical Center in Rotterdam, the Netherlands.
Or to be exact, how you feel is closely related to what you consume.
The gastrointestinal system has been part of brain research for centuries. In the early 1800s, John Abernethy, a popular London physician, argued that “stomach upset” was the root of all mental disorders.
And gastrointestinal symptoms are often reported in people with psychiatric illnesses. Changes in weight and appetite are common in people with depression from adolescence through old age. Anxiety has been linked to an increased risk of nausea, heartburn, diarrhea and constipation. The link between food and mood is there even when we take macaroni and cheese to comfort us during a stressful time.
Interest in the gut-brain axis has been on the rise over the past 20 years. Numerous studies have shown a link between the microbiota living in our intestinal tract and our mind, including our memory, mood and cognitive abilities.
Such research has spawned an industry of probiotics, prebiotics and fermented everything. Scientific names like bacteroides and lactobacillus, two of the most common bacteria found in healthy humans have become household terms.
The health trend has gotten a little ahead of the evidence. Most studies linking depression to the gut, for example, have been conducted on animals, and studies involving human participants have been small.
Yet the evidence so far shows a link between the two. In a remarkable study, titled “Transferring the Blues,” bacteria-free rats given fecal samples from humans diagnosed with major depression became anxious and disinterested in pleasurable activities. Their metabolism of tryptophan, a chemical linked to depression, changed. But the mechanisms behind the mood pathway of microbes — and which bacteria count — have been harder to uncover.
Bacteria that predict depressive symptoms
This new study moves that needle, largely because of its size. The investigators, led by Najaf Amin, who studies population health at the University of Oxford, analyzed data from the Rotterdam study, a decades-long effort to understand the health of the local population.
Amin and his colleagues focused specifically on one phase of this study that included collecting fecal samples from more than 1,000 people. These participants also provided a self-report of depression using a 20-point rating.
The researchers analyzed the data for associations between bacteria populations in the fecal samples with depression assessment scores. They then carried out the same tests using data from 1,539 other Dutch citizens encompassing a range of ethnicities. (Validating the results of one large group in a second large group makes them especially reliable.)
The analysis revealed 16 types of bacteria that the authors called “significant predictors” of depressive symptoms to varying degrees. For example, the study published in Nature Communication, experienced exhaustion Eubacterium ventriosum in depressed people. Interestingly, this same decrease has been spotted in microbiome studies of traumatic brain injury and obesity, both of which are linked to depression, supporting the idea that this species of bacteria has something to do with this. mood disorder.
The study authors also attempted to answer the big question: Does a particular gut flora cause depression? It’s a tricky proposition. Major depressive disorder has been linked to over 80 different genetic mutations and all of these connections are weak.
“There is no gene that causes depression,” said Jane Foster, a UT Southwestern professor of psychiatry who studies the gut-brain connection and was not involved in this study.
The technology to clearly establish causation does not exist. So the researchers turned to a nifty statistical calculation known as Mendelian randomization, which can unravel the direction of an influence when the gene-disease link is strong. This is not the case for depression, which makes the calculation here interesting but not necessarily useful.
Yet the calculation indicated an abundance of a bacterium – Eggerthelle — in people with depression as a possible cause of depressive symptoms. The discovery did not surprise Amin.
Eggerthella, she notes, “is found constantly increased in abundance in the bowels of depressed people.” The result provides evidence that changes in gut flora can trigger depressive symptoms. “We can’t rule out our own DNA as a contributing source,” Foster said. “It’s a combination of the DNA you were born with, your life experiences to date, and your environment.”
Whether flora causes depression or vice versa may be irrelevant. “Causality is not one-sided,” said Jack Gilbert, who directs the Microbiome and Metagenomics Center at the University of California, San Diego, and was not involved in the new study.
Rather, the gut and the brain cycle together. For example, it appears that comfort eating after a stressful event can alter the microbial community in our gut, which exacerbates depressive feelings.
What’s clear, Gilbert said, is that when we’re depressed, the gut microbiome often lacks beneficial flora. “If we can add those elements,” Gilbert said, “maybe we can reinvigorate this cycle.”
Change your diet to improve your mood
This is where food comes into play. An individual who doesn’t consume enough fiber, for example, may experience a decrease in butyrate-producing bacteria, Amin said, leading to stress and inflammation and, potentially, symptoms of depression.
It may seem disappointing that the message of all this work is to eat lots of fruits and vegetables and not too much excess sugar. But the amount of research confirming the power of a healthy gut has become undeniable to even the most hardened skeptic, including Gilbert.
“When the evidence indicates that eating healthy, getting some exercise and taking mindful breaks can have benefits, we should probably listen to that data,” he says.
Research is slowly shedding light on exactly how bacteria communicate with the brain. For example, many of them produce short-chain fatty acids such as butyrate and acetate, which influence brain activity. Others generate a chemical called GABA, deficiencies of which are linked to depression.
These advances mean that diet may not be the only way to improve our gut colonies. Using probiotics to prevent and treat depression could become more of an exact science, eventually leading to effective alternatives to antidepressants, which Gilbert points out are still stigmatized in many communities.
And profiling the bacteria could help identify people at risk for depression, Foster notes. His lab looks for signs in the gut flora indicating which drug is most likely to benefit someone with depression.
All of this research has convinced Uitterlinden that adopting a diet that improves the intestines has only one significant side effect. “You will be happier,” he says.
Do you have a question about healthy eating? E-mail EatingLab@washpost.com and we may answer your question in a future column.
