The close relationship between diet and health is summed up in the popular phrase “we are what we eat”, and that is that inadequate nutrition causes obesity -which was the main pandemic of the 21st century before COVID-19 appeared- and affects negatively to our intestinal microbiota, which contributes to the appearance of numerous physical and mental diseases.
In fact, research has just linked following a diet rich in proline, an amino acid that many foods contain, with a greater chance of suffering from depression. The study has been published in Cell Metabolism and has been carried out by scientists from the Girona Biomedical Research Institute (IDIBGI) and the Pompeu Fabra University (UPF) in Barcelona, who have identified the role that this amino acid plays in the depressive state of humans, mice and flies.
The researchers analyzed the type and amount of amino acids in the diet of study participants, who also answered a questionnaire that measures depressed mood. “We were surprised that what was most associated with depression, evaluated by means of this questionnaire, was the consumption of proline,” says Dr. José Manuel Fernández-Real, from IDIBGI, and also Head of the Endocrinology Section at Hospital Dr. Josep Trueta and director of the Department of Medical Sciences at the University of Girona. When they evaluated plasma metabolomics, proline concentration emerged as one of the metabolites most associated with indicators of depression, confirming the finding.
Relationship Between Gut Bacteria and Depression
Not all participants with a high proline intake reported that their mood was more depressed. And when the scientists studied the gut microbiota of these individuals, they also found a relationship between depression and bacteria, and between depression and bacterial genes associated with proline metabolism. They thus observed that circulating proline levels depended on the microbiota.
When transplanting the microbiota of the participants to mice, they found that those who were most depressed were those that received the microbiota of people with a high amount of proline
“The microbiota of patients with high proline intake but low plasma proline levels was similar to the microbiota associated with low levels of depression and was enriched in bacterial genes involved in proline transport and metabolism,” explained Dr. Dr. Jordi Mayneris-Perxachs, Miguel Servet researcher at IDIBGI.
To determine whether the presence of proline was a cause or consequence of depressed mood, they transplanted the microbiota of the participants into mice, and found that the animals that became most depressed were those that received the microbiota of participants with a high amount of proline, or those of people with a more depressed mood. Different genes associated with proline transport were also found in the brain of these rodents.
“The possibility of transferring the depressive phenotype from humans to mice through microbiota transplantation and the demonstration that this transplantation generates alterations in proline transport reveals that this proline is possibly causally associated with depressed mood”, he states. Dr. Maldonado, from UPF.
They conducted another experiment with fruit flies (Drosophila melanogaster), in which a more depressive mood can be induced. To do this, they isolated two types of bacteria from the microbiota associated with proline consumption and added them to the sterilized food of the flies. The flies that ate a diet with Lactobacillus, which in mice was associated with less depression, showed more desire to overcome difficulties that they later faced, while those that consumed Enterobacter, which in humans is associated with depression, became depressed much more.
Finally, they carried out the same experiment on flies that had been genetically modified to eliminate the channels in them that transport proline to the brain. In this way, proline could not reach the brain, and the flies proved to be very resilient in depression.
“These results demonstrate the importance of proline and its influence on people’s depressed mood, an element that until now had not been taken into account”, Dr. Fernández-Real highlighted. The findings open new avenues for further studies looking at potential diet-based depression treatments.
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