A new study takes an important step forward in understanding the relationship of gut bacteria to what we eat and how we feel
January 31, 2023 at 6:00 a.m. EST
Research has long suggested a link between our diet and our mental health. The
gut microbiome —
the collective genome of trillions of bacteria that live in the
intestinal tract that are created largely by what we eat and drink —
appears to influence our mood and mind-set.
But human studies large enough to pinpoint what bacteria matter, if they matter at all, have been missing.
That’s
slowly changing. The largest analysis of depression and the gut
microbiome to date, published in December, found several types of
bacteria notably increased or decreased in people with symptoms of
depression.
“This
study provides some real-life evidence that you are what you eat,” says
study author Andre Uitterlinden, who researches genetics at Erasmus
Medical Centre in Rotterdam, Netherlands.
Or to be exact, how you feel is closely related to what you consume.
The
gastrointestinal system has been featured in brain research for
centuries. In the early 1800s, John Abernethy, a popular London
physician, held that “
gastric derangement” was the root of all mental disorders.
And gastrointestinal symptoms often are
reported in people with psychiatric illness. Weight and appetite changes are common among people with depression, from
adolescence to
older age. Anxiety has been
tied to
a heightened risk of nausea, heartburn, diarrhea and constipation. The
link between food and mood is there even when we reach for macaroni and
cheese to comfort us during a stressful time.
Interest
in the gut-brain axis has had a resurgence in the past 20 years. A host
of studies has pointed to a connection between the microbiota living in
our intestinal tract, and our minds, including our
memory,
mood and
cognitive skills.
Such research has spawned an industry of probiotics, prebiotics and fermented everything. Scientific names like bacteroidetes and lactobacillus, two of the most common bacteria found in healthy humans, have become household terms.
The
health trend has gotten a bit ahead of the evidence. Most of the
studies linking depression and the gut, for example, have been in
animals and studies involving human participants have been small.
Still, the evidence thus far shows a link between the two. In one noteworthy
study,
entitled “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 connected to
depression, changed. But the mechanics behind the microbe-mood pathway — and which bacteria matter — has 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 researches population health at
Oxford University, 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 a phase of this study that
included fecal sample collection from more than 1,000 individuals. These
participants also provided a self-report on depression using a 20-item
assessment.
The
researchers parsed the data for associations between the bacteria
populations in the fecal samples with scores from the depression
assessment. They then conducted the same tests using data from another
1,539 Dutch citizens encompassing 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 depressive symptoms to varying degrees. For
example,
the study, published in
Nature Communications, found a depletion of
Eubacterium ventriosum among people who were depressed. Interestingly, this same decrease has been spotted in microbiome studies of
traumatic brain injury and
obesity, both of which are
tied to
depression, supporting the notion that this species of bacteria has something to do with this mood disorder.
The
study authors also took a stab at answering the big question: Do any
particular gut flora cause depression? It’s a tricky proposition. Major
depression disorder has been linked to more than 80 different genetic
mutations and all of these connections are weak.
“There’s
no gene that causes depression,” said Jane Foster, professor of
psychiatry at UT Southwestern, who studies the gut-brain connection and
was not involved with this study.
Technology
to clearly establish causation does not exist. So the researchers
turned to a crafty statistical calculation known as Mendelian
randomization, which can tease out the direction of an influence when
the gene-disease connection is strong. That’s not the case with
depression, which makes the calculation here interesting but not
necessarily useful.
Still, the calculation did point to an abundance of one bacteria — Eggerthella — in people with depression as a possible cause of depressive symptoms. The finding didn’t surprise Amin.
Eggerthella,
she notes, “is found to be consistently increased in abundance in the
guts of depressed individuals.” The result provides evidence that
changes in the gut flora may trigger depressive symptoms. “We cannot
exclude our own DNA as a contributing source,” Foster said. “It’s a
combination of the DNA you were born with, your experiences in life to
date, and your environment.”
Whether
the flora cause the depression or vice versa may be beside the point.
“Causation isn’t a one-way street,” said Jack Gilbert, who directs the
Microbiome and Metagenomics Center at the University of California at
San Diego, and was not involved with the new study.
Rather,
the gut and brain cycle together. For instance, it appears that comfort
eating after a stressful event can change the microbial community in
our intestines, which in turn exacerbates depressed feelings.
What
is clear, Gilbert said, is that when we are depressed, the gut
microbiome is often missing beneficial flora. “If we can add those
elements back in,” Gilbert said, “maybe we can re-energize that cycle.”
Changing your diet to improve your mood
This is where diet enters the picture. An individual who does not 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.
“When
the evidence points to the fact that eating healthy, doing a little bit
of exercise and taking mindfulness breaks can have benefits, we should
probably listen to that data,” he says.
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
influence brain activity. Others generate a chemical called GABA, deficits of which are
linked to
depression.
This
progress means that diet may not be the only way to improve our gut
colonies. The use of probiotics to prevent and treat depression could
become more of an exact science, leading eventually to effective
alternatives to antidepressants, which, Gilbert points out, still carry a
stigma in many communities.
And
profiling the bacteria could help identify people at risk for
depression, notes Foster. Her lab is searching for signs among gut flora
indicating what drug is most likely to benefit someone suffering from
depression.
All
this research has convinced Uitterlinden that adopting a gut-improving
diet comes with just one significant side effect. “You’ll get happier,”
he said.
Do you have a question about healthy eating? Email EatingLab@washpost.com and we may answer your question in a future column.
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