Studies have long indicated a connection between nutrition and our mental health.
It seems that the gut microbiome – the collective genome of trillions of bacteria that live in the intestinal system that are formed mainly from what we eat and drink – affects our mood and mood. But we lack studies large enough to indicate which bacteria, if any, are important.
Slowly it is changing. The largest analysis of depression and the gut microbiome to date, published in December, found numbers of bacterial types that increased or decreased markedly in people with symptoms of depression.
“This study provides some real-life evidence that we are what we eat,” says study author Andre Otterlinden, who studies genetics at the Erasmus Medical Center in Rotterdam, the Netherlands.
Or rather, how we feel is closely related to what we consume.
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The digestive system has been featured in brain research for centuries. At the beginning of the 18th century, John Abernathy, a popular London physician, stated that “stomach disturbance” was the root of all mental disorders. Gastrointestinal symptoms are often reported in people with psychiatric illness. Changes in weight and appetite are common in people with depression, from adolescence to old age. Anxiety has been linked to an increased risk of nausea, heartburn, diarrhea and constipation. The connection between food and mood is also present when we reach for mac and cheese or a pint of Ben & Jerry’s to comfort us during a difficult time.
The gut-brain axis has received renewed interest in the last 20 years. A series of studies have indicated a connection between the microbiota living in our intestinal system, and our brain; including our memory, mood and cognitive skills.
Such research has spawned an industry of probiotics, prebiotics and more. Scientific names such as Bacteroidetes and Lactobacillus, two of the most common bacteria found in healthy humans, have become household terms.
The health trend was slightly ahead of the evidence. Most of the studies linking depression to the digestive system, for example, have been on animals. Studies involving human participants have been small.
Still, the evidence so far points to a connection between the two. In one noteworthy study, titled “Transferring the Blues,” germ-free rats given stool samples from humans diagnosed with major depression became anxious and disinterested in pleasurable activities. Their metabolism of tryptophan, a chemical associated with depression, was altered. But the mechanics behind the mood pathway of bacteria – and the bacteria matter – have been harder to uncover.
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This new study moves the needle, mostly because of its size. The researchers, 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 her colleagues focused specifically on the phase of the study that involved collecting stool samples from more than 1,000 people. These participants also provided a self-report of depression using a 20-item assessment. The researchers analyzed the data regarding relationships between the bacterial populations in the stool samples and scores from the depression assessment. They then conducted the same tests using data from another 1,539 Dutch citizens, spanning a range of ethnicities. (Validating the findings from one large group in a second large group makes them particularly reliable.)
The analysis revealed 16 types of bacteria that the authors called “important predictors” of varying degrees of depressive symptoms. For example, the study, published in Nature Communications, found a depletion of Eubacterium ventriosum in people who were depressed. An interesting fact is that the same decrease was observed in microbiome studies of traumatic brain injury and obesity, both of which are associated with depression, supporting the notion that this type of bacteria has a connection to this mood disorder.
The authors of the study also nailed the answer to the big question: Does a certain gut flora cause depression? it is complicated. 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 the gut-brain connection and was not involved in this study.
Technology to clearly establish a causal relationship does not exist. So the researchers turned to a sneaky statistical calculation, known as Mendelian randomization, which can demonstrate the direction of effect when the link between genes and diseases is strong. This is not the case in depression, which makes the calculation here interesting but not necessarily useful.
Still, the calculation did point to an abundance of one bacteria – Eggertella – in people with depression, as a possible cause of depressive symptoms. The finding did not surprise Amin. Eggertella, she notes, “has been consistently found to grow abundantly in the intestines of depressed individuals.” The result provides evidence that changes in gut flora may trigger depressive symptoms. “We can’t say for sure that our DNA is not a donor source,” Foster said. “It’s a combination of the DNA we were born with, our experiences in life to date and our environment.”
Does the flora cause depression or vice versa? This question may miss the point. “Causality is not one-way,” said Jack Gilbert, director of the Center for Microbiome and Metagenomics at the University of California, San Diego, who was not involved in the new study. Instead, the gut and brain move together. For example, it appears that “comfort eating” after a stressful or sad event can change the bacterial community in our gut, which leads to worsening feelings of depression.
What is clear, Gilbert said, is that when we are depressed, the gut microbiome often lacks beneficial flora. “If we can add those elements back in,” Gilbert said, “maybe we can restart that cycle.”
Changing your diet to improve your mood
This is where diet comes into play. A person who doesn’t consume enough fiber, for example, may experience a decrease in butyrate-producing bacteria, Amin said, leading to stress and inflammation, and possibly symptoms of depression.
It may be disappointing that the message from all this work is to eat lots of fruit and vegetables and not consume too much sugar. But the sheer amount of research confirming 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 eating healthy, exercising and taking breaks from the mind can have benefits, we should probably listen to that data,” he says.
The research is slowly illuminating exactly how bacteria talk to the brain. For example, many of them produce short-chain fatty acids such as butyrate and acetate, which affect brain activity. Others produce a chemical called GABA, a lack of which in the body is linked to depression.
This progress means that diet cannot be the only way to improve our gut colonies. The use of probiotics to prevent and treat depression may become a more exact science, eventually leading to effective alternatives to antidepressants, notes Gilbert, which still carry stigmas in many communities.
Profiling the bacteria can help identify people at risk for depression, Foster notes. Her lab looks for signs among the gut flora that indicate which drug is likely to benefit someone suffering from depression. That research convinced Otterlinden that adopting a gut-improving diet comes with one significant side effect: “You’ll be happier,” he said.