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Diet and lifestyle

Intestinal disorder may increase the risk of depression and bipolar disorder

A Danish study of twins shows that the composition of their intestinal bacteria may strongly influence the risk of developing affective mental disorders such as depression and bipolar disorder. The research also shows that people with depression appear to have fewer of certain intestinal bacteria that are normally associated with being generally healthy. Finally, the research may indicate why people at high risk of developing depression or bipolar disorder are so vulnerable.

We have never been more closely linked to our intestines than we are today. Researchers are discovering just how important the composition of bacteria in the intestines is for our health. This influences our immune response, the risk of obesity and cardiovascular disease, the risk of asthma, the risk of developing type 2 diabetes and much, much more.

The reason why intestinal bacteria are important for our health is the unique collaboration between the bacteria and the rest of the body, including the brain. The intestinal system is the primary mechanism for managing the exchange of both beneficial and harmful substances. This is why we react to the composition of our intestinal bacteria and whether the health-promoting bacteria are thriving; conversely, our intestinal bacteria react to our behaviour, such as diet and exercise. These lifestyle habits are also closely linked to our mental health.

In relation to our health, a new study shows that the composition of intestinal bacteria may be a key trigger for people developing mental disorders such as depression and bipolar disorder.

Researchers from the mental health services of the Capital Region of Denmark, the University of Copenhagen and others examined pairs of identical twins and discovered that twins lacking certain bacteria in their intestines may have a greater risk of developing depression and bipolar disorder.

“We have always wondered why one identical twin often develops depression or bipolar disorder and the other does not. This suggests factors other than genes. We discovered that the composition of intestinal bacteria may contribute to the risk of developing mood disorders,” explains first author Maj Vinberg, Clinical Research Associate Professor, Department of Clinical Medicine, University of Copenhagen and Rigshospitalet.

The new study has been published in Acta Psychiatrica Scandinavica.

A twin study

To examine whether or how intestinal bacteria are associated with the risk of developing depression and bipolar disorder, the researchers collected information on identical twins with these disorders from the Danish Twin Registry and the Danish Psychiatric Central Research Registry. They identified the pairs of identical twins in which one or both had depression or bipolar disorder.

The study was based on earlier research comparing pairs of healthy identical twins with twins in which one twin had depression or bipolar disorder, which found that the healthy sibling of the twin with the disorder often had several risk factors for depression. The risk factors included an elevated level of stress hormones, mildly poorer concentration and impaired memory and discreet symptoms of anxiety and depression.

However, not every pair of identical twins develops the disorders by any means. This suggests that a healthy identical twin of a sibling with a disorder may benefit from protective factors or may have overcome the contributory factor or factors so far.

In the new study, the researchers divided the identical twins into three groups:

• Both twins had depression or bipolar disorder.

• One twin had depression or bipolar disorder.

• Both twins were healthy and had no history of depression or bipolar disorder.

Strong genetic component

The researchers collected stool samples from 128 twins. They hypothesized that the intestinal bacteria of the healthy twins would differ from those of the twins who had depression or bipolar disorder.

The researchers also aimed to determine the composition of the intestinal bacteria among the healthy twins who had a high risk of developing depression or bipolar disorder, defined as their twin being diagnosed with one of the disorders. “Genetic factors are well documented as a risk factor for developing depression or bipolar disorder. For example, one participant was the identical twin of a sister who had been hospitalized with depression. She said that the doctor who treated her sister had explained to her that he expected to have to treat her in the coming years because depression has a strong genetic component. Nevertheless, genetics do not explain everything, because the heritability is not 100% deterministic. Several protective factors enable some people to defy genetics,” says Maj Vinberg.

Unfavourable composition

The researchers analysed the presence of various types of bacteria in the stool samples by analysing the whole genome of the intestinal bacteria and determining which bacteria were present and absent based on these genetic data.

The results were as follows.

Healthy twins with a low risk of developing depression or bipolar disorder had an extremely varied composition of intestinal bacteria compared with the twins who had depression or bipolar disorder and the siblings of twins who had depression and bipolar disorder, categorized as high-risk twins. Varied composition of intestinal bacteria is a sign of being generally healthy, and this also seems to apply to these affective disorders.

Conversely, the composition of the intestinal bacteria of twins in the high-risk group for developing depression or bipolar disorder did not significantly differ from that of twins who had depression or bipolar disorder.

The last result may explain why people at risk of developing these affective disorders have a higher risk: intestinal bacteria may play a role, and the composition of the intestinal bacteria of these twins is unfavourable.

“The interesting thing is that the intestinal bacteria differ between twins who are healthy and twins who are predisposed to developing depression and bipolar disorder. This indicates that the composition of the intestinal bacteria may be associated with the risk of developing these disorders,” says Maj Vinberg.

Lack of certain bacteria may result in a disorder

The most interesting discovery was that people who had depression or bipolar disorder or who were at risk of developing the disorders specifically lacked bacteria from the Christensenellaceae family.

Having many of the Christensenellaceae family of intestinal bacteria is generally good and indicates health and normal weight. A previous twin study further suggested that the presence of Christensenellaceae is associated with the genetics of the host.

“Interestingly, Christensenellaceae was lacking among the twins who had a disorder and among those with high risk. The intestine and the bacteria that live there naturally secrete beneficial substances into our blood, help to protect us from such things as unwelcome and potentially dangerous microorganisms and break down and metabolize what we eat. If genes help to regulate the composition of intestinal bacteria, our findings about identical twins may therefore help to elucidate the complex chain of events that links diet and mental disorders,” explains Maj Vinberg.

Dietary advice may protect

The researchers’ new results also support the theory that intestinal bacteria may be associated with developing depression, bipolar disorder and other illnesses by promoting mild but chronic inflammation in the body. This inflammation may arise if the composition of intestinal bacteria does not protect us from absorbing the unhealthy things from a diet of the wrong type or poor quality. This is because Christensenellaceae bacteria seem to regulate how we absorb and distribute fat.

“A subgroup of people with depression or bipolar disorder seems to have a slightly elevated concentration of inflammation biomarkers. This mild inflammation is more often present if people are overweight and affects the brain. We cannot say that food can cause depression, but we can say that a person can be more or less vulnerable to whether food can cause depression,” says Maj Vinberg.

Maj Vinberg explains that the study was not large enough to make definite conclusions, but the findings support the need for larger and more comprehensive studies on how the composition of intestinal bacteria is associated with depression and bipolar disorder.

The researchers will initially carry out large observational studies and preferably follow-up studies to determine whether people who lack the Christensenellaceae bacteria develop the disorders.

In the long term, it could also be useful to develop intervention studies examining whether dietary interventions can minimize the risk of developing depression or bipolar disorder among people predisposed to developing these disorders.

“This does not mean that everyone genetically predisposed to depression or bipolar disorder should eat a raw food diet. Many other factors are important. However, long-term efforts may enable us to examine whether comprehensive dietary advice and lifestyle interventions can prevent people from developing depression and bipolar disorder,” concludes Maj Vinberg.

Remitted affective disorders and high familial risk of affective disorders associate with aberrant intestinal microbiota” has been published in Acta Psychiatrica Scandinavica. Oluf Borbye Pedersen, Professor, Novo Nordisk Foundation Center for Basic Metabolic Research, participated in the study.

Maj Vinberg
Clinical research associate professor
Department of Clinical Medicine participates in teaching, research and dissemination of knowledge within the clinical field. The department undertakes undergraduate as well as postgraduate training of especially medical students in Eastern Denmark. The department employs 200 clinical professors, app. 500 clinical associate professors, a number of clinical lecturers and tutors and around 700 PhD students.