The connection between our food, the gut microbiome and depression
That is slowly changing. The largest analysis of depression and the gut microbiome to date, published in December, found that several types of bacteria were significantly increased or decreased in people with depressive symptoms.
“This study provides some real-life evidence that you are what you eat,” says study author Andre Uitterlinden, who researches genetics at the Erasmus Medical Center in Rotterdam, the Netherlands.
Or more precisely, how you feel is closely related to what you consume.
The gastrointestinal system has been the subject of brain research for centuries. In the early 1800s, John Abernethy, a popular London physician, believed that “stomach disorder” was the root of all mental disorders.
And gastrointestinal symptoms often are reported in persons with psychiatric diseases. Changes in body weight and appetite are common among people with depression, from youth to older age. It was anxiety related to increased risk of nausea, heartburn, diarrhea and constipation. The connection between food and mood exists even when we reach for macaroni and cheese to comfort us during stressful times.
Interest in the gut-brain axis has resurged in the last 20 years. A number of studies have pointed to a connection between the microbiota living in our digestive tract and our minds, including memory, mood and cognitive abilities.
Such research has spawned the industry of probiotics, prebiotics and everything fermented. Scientific names like bacteroidetes and lactobacillus, two of the most common bacteria found in healthy people have become household expressions.
The health trend has slightly overtaken the evidence. Most studies linking depression and the gut, for example, have been in animals, and studies involving humans have been small.
However, the evidence so far shows a link between the two. In one worth mentioning study, titled “Transferring the Blues,” germ-free rats given fecal samples from people diagnosed with major depression became anxious and disinterested in pleasurable activities. Their metabolism of tryptophan, a chemical associated with depression, changed. But figuring out the mechanics behind the microbe-mood pathway—and which bacteria matter—has been more difficult.
Bacteria that predict symptoms of depression
This new study moves that needle, largely because of its size. The researchers, led by Najaf Amin, who researches population health at the University of Oxford, analyzed data from the Rotterdam Study, a decades-long effort to understand the health of local populations.
Amin and her colleagues focused specifically on the phase of this study that involved collecting fecal samples from more than 1,000 individuals. These participants also self-reported depression using a 20-item assessment.
The researchers analyzed the data for associations between bacterial populations in fecal samples and scores from depression assessments. They then ran the same tests using data from another 1,539 Dutch citizens spanning a range of ethnic groups. (Confirmation of the findings of one large group in another large group makes them particularly reliable.)
The analysis revealed 16 types of bacteria that the authors called “important predictors” of depression symptoms to varying degrees. For example, studyPublished in Nature Communications, depletion found Eubacterium ventriosum among people who were depressed. Interestingly, this same reduction was observed in microbiome studies traumatic brain injury and obesityand both are tied to depressionsupporting the idea that this type of bacteria has something to do with this mood disorder.
The authors of the study also tried to answer the big question: Does any particular gut flora cause depression? That’s a tricky proposition. Major depressive disorder has been linked to more than 80 different genetic mutations, and all of these links are weak.
“There is no gene that causes depression,” said Jane Foster, a professor of psychiatry at UT Southwestern, who studies gut-brain connections and was not involved in this study.
The technology to clearly establish causality does not exist. So the researchers turned to a tricky statistical calculation known as Mendelian randomization, which can reveal the direction of influence when the link between a gene and a disease is strong. This is not the case with depression, which makes this calculation interesting, but not necessarily useful.
However, the calculation indicated an abundance of one bacterium – Eggerthella — in people with depression as a possible cause of depressive symptoms. The discovery did not surprise Amin.
Eggerthella, she notes, “was found to be consistently increased in abundance in the gut of depressed individuals.” The result provides evidence that changes in gut flora can trigger symptoms of depression. “We cannot rule out our own DNA as a contributing source,” Foster said. “It’s a combination of the DNA you were born with, your past life experiences and your environment.”
It doesn’t matter if flora causes depression or vice versa. “Causality is not a one-way street,” said Jack Gilbert, who directs the Center for Microbiome and Metagenomics at UC San Diego and was not involved in the new study.
Instead, the gut and brain cycle together. For example, comfort food after a stressful event appears to alter the microbial community in our gut, which in turn exacerbates feelings of depression.
What’s clear, Gilbert said, is that when we’re depressed, the gut microbiome often lacks beneficial flora. “If we can add those elements back in,” Gilbert said, “maybe we can start that cycle again.”
Changing your diet to improve your mood
This is where diet comes into play. An individual who doesn’t consume enough fiber, for example, may experience a reduction in butyrate-producing bacteria, Amin said, leading to stress and inflammation and, potentially, depressive symptoms.
You may feel disappointed that the message of all this work is to eat lots of fruit and vegetables and not too much sugar. But the sheer amount of research supporting the power of a healthy gut has become undeniable to even the most hardened skeptic, including Gilbert.
“When the evidence points to the fact that a healthy diet, a little exercise and mindfulness breaks can be beneficial, we should probably listen to that data,” he says.
Research is slowly revealing exactly how bacteria talk to the brain. For example, many of them produce short-chain fatty acids such as butyrate and acetate, which influence brain activity. Others make a chemical called GABA, which is deficient connected to depression.
This advance means that diet may not be the only way to improve intestinal colonization. Using probiotics to prevent and treat depression could become a more exact science, eventually leading to effective alternatives to antidepressants, which, Gilbert points out, still carry a stigma in many communities.
And bacterial profiling could help identify people at risk for depression, Foster notes. Her lab looks for cues among gut flora that indicate which drug is most likely to benefit someone suffering from depression.
All this research convinced Uitterlinden that adopting a gut-improving diet had only one significant side effect. “You’ll be happier,” he said.
Do you have a question about healthy eating? E-mail [email protected] and we may answer your question in a future column.