Proline, Depression, and the Gut Microbiome
I recently had a fascinating article brought to my attention and a spent some time trying to analyze it and better understand its implications. The study was titled Microbiota Alterations in Proline Metabolism Impact Depression. It can be found in the May, 2022 issue of Cell Metabolism.
www.sciencedirect.com/science/article/pii/S1550413122001280
Being a psychologist by training, I am always particularly interested in how what we eat impacts our psychological symptoms and emotional well-being. As this study also looked at microbiome status, a particular area of personal interest, it was a fascinating read with hopeful implications for future depression treatment. Thank you, Rob, for bringing it to my attention.
Here are my take-aways from the study:
Microbiome status impacts depression through the gut-brain axis. I am thrilled that the microbiome is being studied as a possible means of attenuating depressive symptoms.
The study “revealed significant differences in the microbiome composition between non-depressed and depressed subjects." We touched on this briefly in our discussion of chocolate. Depressed folks have a different microbiome composition than non-depressed individuals. This has been seen in previous studies, and it was noted in this group of subjects, as well.
Individuals with gut dysbiosis and intestinal permeability have been seen to have higher levels of depression. “Gut dysbiosis triggers a pro-inflammatory state in the host by increasing the permeability of the gut barrier, facilitating the translocation of bacterial antigens into the circulation leading to low-grade inflammation. Increased intestinal barrier permeability has been associated with altered gut microbiota in anxiety or depression.”
High proline consumption was the dietary factor found to have the strongest impact on depression.
The researchers hypothesized that proline impacted depression by impacting Gamma-aminobutyric acid (GABA) transmission. GABA is a neurotransmitter known for producing a calming effect. “Current findings point toward a potential role of the microbiome in depression through glutamate/GABA metabolism, compatible with the glutamate hypothesis of depression...Proline accumulation has been shown to disrupt GABA production and glutamate release and impair synaptic transmission."
“Circulating proline levels were dependent on the gut microbiome composition and functionality…Patients who despite consuming high proline levels had low circulating proline levels had a microbiota composition consistent with that associated with lower depression scores. The microbiota of patients with a high consumption of proline but low circulating proline levels was also enriched in bacterial functions involved the transport and metabolism of proline." In essence, if you generally have low baseline levels of circulating proline, you typically have less depression and you are better able to metabolize excess proline when you do encounter it.
To find out if the presence of proline was a cause or a consequence of depressive mood, participants' microbiota was transplanted into mice. The rodents that became more depressed had received the microbiota of participants with high proline, or more depressed subjects. A secondary confirming study was conducted in fruit flies.
BOTTOM LINE: The researchers proposed that “diets with reduced proline content may have a strong impact in ameliorating depressive symptomatology."
So which foods are highest in proline? According to the US Department of Agriculture, the foods highest in proline are: Soy milk, gelatin, pork skins, dairy products, eggs, fresh pork, bone broth, chicken, beef (both grass fed and feed lot), seaweed, mollusks, fish. www.fdc.nal.usda.gov/fdc-app.html#/?component=1226
And, which foods are low in proline? Coffee, tea, pears, apples, noodles, pickles, pineapples, nectarines, peaches, cucumber, melon, onions, strawberries, tomatoes, blueberries, carrots, plums, jackfruit, pumpkin, beets, squash, taro, turnips, celery, persimmons, figs, jicama, bananas, loquats, beans, nuts, plantains, cabbage, peppers, sweet potatoes, mushrooms, etc. Whole plant foods are low in proline.
Proline seems to be an exciting area of future research in helping to alleviate depression. As this was the first study linking proline and depression, clearly more research is needed. Until then, the researchers recommend a diet with low proline content if you are interested in ameliorating depressive symptomatology.
Finally, as proline appears to be moderated by gut microbiome status, with healthier guts being linked with less depression and an ability to metabolize excess dietary proline, focusing on gut microbiome healing is important. How to we heal our guts? We eat more plants.
Thank you so much to Rob for bringing this fascinating article to my attention. It was a joy to read in full and to dissect.
Eat More Plants!
🌱💕