An Orange a Day to Keep Depression Away? The Secret Lies in the Microbiome

An Exceptional Fruit

In English-speaking countries, there’s a popular saying: "An apple a day keeps the doctor away." However, current data suggest citrus fruits, such as oranges, could potentially claim a similar status.

It seems that their health benefits are not limited only to their high content of vitamin C, flavonoids, or dietary fiber. Consuming one average-sized orange per day may reduce the risk of developing depression by 20%. Such an effect was not observed with other types of fruits or vegetables, nor with specific combinations of fruits and vegetables.

Building on Previous Research

Researchers from Harvard University expanded upon Chang et al.’s 2016 study, which had already pointed out the potential of citrus fruits in reducing depression risk. The Harvard researchers leveraged the extensive longitudinal data from the Nurses' Health Study II (NHS2), an ongoing study in the USA collecting population data since 1989, aimed at identifying risk factors for major chronic diseases among women. It involves 32,427 nurses who provide detailed information every two years regarding lifestyle, diet, medications, and overall health.

In a subset of 207 participants, stool samples were regularly collected and genetically sequenced to map the bacterial composition of the gut microbiome. Researchers examined associations between daily citrus consumption and bacterial presence. They identified abundant amounts of approximately 15 bacterial species, most notably Faecalibacterium prausnitzii. Conversely, significantly lower amounts of this bacterium were found among women who had experienced depression. The researchers then validated their findings in a male population using a similar Men’s Lifestyle Validation Study involving 307 participants.

New Insights into the Gut-Brain Axis

Faecalibacterium prausnitzii activates the S-adenosyl-L-methionine cycle I metabolic pathway, leading to the production of two neurotransmitters: serotonin and dopamine. These neurotransmitters regulate digestion but can also travel to the brain, improving mood. While the gut-brain axis is a commonly discussed topic, this discovery adds another piece to understanding its functioning. Previously, F. prausnitzii had been linked, for instance, to a reduced risk of developing intestinal inflammation.

A Future Natural Treatment for Depression?

According to study co-author Raaj Mehta, MD, MPH, citrus fruits could become part of depression-management strategies, especially since there’s significant demand for depression treatments with fewer side effects. Medication often proves ineffective; 70% of depression patients do not respond to initial antidepressant treatment, or they experience side effects preventing continuation.

Additionally, depression increases the risk of premature death, including from comorbidities. Adjusting diet appears as the simplest solution. In this respect, the Mediterranean diet stands out, having been proven to reduce depression risk by up to 35%. However, evidence regarding specific food groups and the mechanisms behind their protective roles was still lacking.

The next step to confirm these findings involves conducting proper randomized, placebo-controlled clinical trials to verify the causal link between citrus fruit consumption and depression risk.

According to gastroenterologist Rudolph Bedford, MD, from Saint John’s Health Center in Santa Monica, California, current knowledge about the gut microbiome's impact on mental health is "just scratching the surface." Therefore, we may soon replace the apple proverb with the more general idea: "You are what you eat."

Editorial Team, Medscope.pro

Sources:
1. Samuthpongtorn et al. F. prausnitzii potentially modulates the association between citrus intake and depression. Microbiome 2024, 12(1), 237, doi: 10.1186/s40168-024-01961-3.
2. Chang et al. Dietary flavonoid intake and risk of incident depression in midlife and older women. The American Journal of Clinical Nutrition 2016, 104(3), 704-714, doi: 10.3945/ajcn.115.124545.
3. Sidik S. Forget apples—researcher outlines how an orange a day may reduce depression risk by 20%. Medicalxpress.com. 24 Feb 2025. Available at: www.medicalxpress.com/news/2025-02-apples-outlines-orange-day-depression.html
4. Anderson N. Citrus Fruit Consumption Helps Protect against Depression via Gut Microbiome: Study. Scinews.com. 26 Feb 2025. Available at: www.sci.news/medicine/citrus-depression-13701.html
5. Pelc C. Eating citrus fruit like oranges tied to 20% lower depression risk. Medicalnewstoday.com. 28 Feb 2025. Available at: www.medicalnewstoday.com/articles/eating-citrus-fruit-like-oranges-tied-to-20-lower-depression-risk