Persistent sadness, long-lasting loss of interest or pleasure in activities that used to be enjoyable: depressive disorder, also known as depression, is a common mental disorder thought to affect more than 280 million people worldwide. Traditional treatments such as antidepressants often fail to produce the desired effect. Some patients even experience worsening symptoms or unwanted side effects.

What if the solution to the blues lay not in a pill, but in a bowl of fruit? A recent study ¹ suggests that oranges, lemons, clementines, grapefruit and other citrus fruits may have an antidepressant effect.

22% reduction in depression

This is the finding of a team of researchers ¹ who studied the impact of consumption of citrus fruit on depression, using data from over 32,000 women in an American cohort followed for 14 years. Their discovery? Higher consumption of citrus fruit was associated with a 22% reduction in the risk of depression.

The 20% of women who ate the most citrus fruit were far less likely to fall into clinical depression. How can such an effect be explained? By our gut microbiota, the collection of bacteria and other micro-organisms that colonize our gut, say the researchers.

A caring microbiota

So it seems that this little world that populates our digestive tract (also!) plays a crucial role in our mental well-being. And all via what scientists call the gut-brain axis. How? It would seem that flavonoids, natural substances found in citrus fruits, can modulate our gut flora, in particular by promoting the growth of Faecalibacterium prausnitzii. This bacterium is thought to be capable of producing a molecule called SAM (S-Adenosyl-L-methionine).

And here's where it gets interesting: SAM may help reduce the activity of an enzyme that breaks down the "happy hormones," in this case serotonin and dopamine. More citrus and F. prausnitzii, less enzyme destruction, more neurotransmitters available...and a happier brain!

Endometriosis affects around 10% of women of childbearing age, with symptoms including dysmenorrhea, dysuria, pelvic pain, and reduced fertility or even infertility.

One diagnostic tool, laparoscopy, is invasive and delays treatment. Hence the hope of one day finding a non-invasive marker.

We may have to look no further, thanks to a study by Australian researchers who examined three microbiomes (oral, gut, and vaginal) to identify a bacterial signature of endometriosis.

Greater diversity in oral and gut microbiota

A total of 64 women were included in the study ¹ :

• 24 with gynecological symptoms but laparoscopically confirmed no-endometriosis (N-ENDO)
• 21 with laparoscopically confirmed endometriosis (ENDO)
• and 19 controls with no known gynecological symptoms or infertility concerns (HC)

Alpha-diversity (sidenote: Alpha diversity Number of species coexisting in a given environment )  analyses revealed initial differences: the HC healthy controls had a more diverse oral and gut (but not vaginal) microbiota than the N-ENDO and ENDO groups.

Bacteria that signal disease...

Above all, the vaginal flora of the ENDO group was richer in Escherichia, Enterococcus, and Tepidimonas.

Their stools contained more Lactobacillus, but also more Phascolarctobacterium, a bacterium known to be more abundant in the peritoneal fluid of these patients, raising the hypothesis of a possible bacterial translocation from the gut to the peritoneum.

Furthermore, Fusobacterium was more abundant in the oral cavity: could this opportunistic pathogen, implicated in periodontal disease, explain the higher incidence of gum inflammation in women suffering from endometriosis?

... and its severity

Microbiota also appear to signal the severity of endometriosis:

• stools show a greater abundance of Actinomyces in cases of minimal/mild endometriosis (stages 1 and 2) and of Paraprevotellaceae in cases of moderate/severe endometriosis (stages 3 and 4);
• the oral microbiota is enriched with Cardiobacterium in cases of minimal/mild endometriosis and with Fusobacterium in cases of moderate/severe endometriosis;
• the vaginal flora contains more Blautia, Dorea, Collinsella, and Eubacterium in moderate/severe endometriosis.

L'endométriose, cette maladieEndometriosis is a condition where the endometrial tissue which usually lines the inside of the uterus instead grows outside the uterus. It affects around 10% of women of childbearing age. Unfortunately, one form of diagnosis – laparoscopy (sidenote: Laparoscopy Laparoscopy is a technique for exploring and treating organs in the abdominal cavity, usually performed under general anesthesia. Through small incisions in the abdominal wall, the surgeon can access the interior of the abdomen to diagnose (e.g. endometriosis) or treat (removal of endometriosis lesions, treatment of ectopic pregnancy, acute appendicitis, etc.). Explore DiZerega GS, Rodgers KE, Peritoneal Fluid. The Peritoneum. 1992. pp 26-56 Sprin… )  – is invasive and delays treatment, which, in the absence of a cure, is limited to reducing painful symptoms. The good news is that Australian researchers may have discovered a non-invasive alternative form of diagnosis. ¹

Can the microbiota signal endometriosis?

The researchers looked at three microbiomes: oral, gut, and vaginal. Their aim? To identify a bacterial signature of endometriosis. And they succeeded! The healthy controls had a more diverse oral and gut (but not vaginal) microbiota than women suffering from endometriosis. More importantly, changes in certain bacteria were observed in women suffering from endometriosis.

For example, their vaginal flora contained more Escherichia, Enterococcus, and Tepidimonas. Their gut microbiota was richer in Lactobacillus and Phascolarctobacterium, bacteria already found in the patients’ peritoneal fluid (sidenote: Peritoneal fluid Fluid found in the peritoneal cavity, i.e., inside the membrane surrounding the abdominal organs. It acts as a lubricant, preventing friction between the organs during digestion. DiZerega GS, Rodgers KE, Peritoneal Fluid. The Peritoneum. 1992. pp 26-56 Springer New York ) , suggesting these bacteria may migrate from the digestive tract to the peritoneum. In the oral microbiota, Fusobacterium (sidenote: Fusobacterium Fusobacterium is a genus of filamentous bacteria that lives in the mouth (dental plaque), digestive system, vagina and, to a lesser extent, the uterine cavity. This pathogenic bacterium is implicated in periodontitis (inflammation at the base of the tooth) and colorectal cancer. )  was more prevalent in women with moderate to severe endometriosis. This bacterium is implicated in periodontitis, an inflammation of the gums that often affects women suffering from endometriosis. Could Fusobacterium thus be the link between endometriosis and gingivitis? Perhaps.

Endometriosis and its severity

The researchers also found differences according to the severity of endometriosis. For example, Actinomyces was more abundant in the digestive tract in minimal/mild endometriosis, while Paraprevotellaceae was associated with more severe forms. In the oral microbiota, Cardiobacterium was more prevalent in mild forms of endometriosis and Fusobacterium in severe forms. In the vaginal microbiota, severe endometriosis was associated with an increased presence of Blautia, Dorea, Collinsella, and Eubacterium.

Here's a quick look at how Prof. Sokol answers this question from his patients

The gut microbiota is often called the "second brain" for several reasons. First, the gut is the organ that contains the most neurons after the brain. It contains about 500 million neurons forming what is called the enteric nervous system.

Secondly, the gut interacts with the brain through different mechanisms: nerve connections,  chemical molecules produced in the gut by human cells or by the microbiota, which can act either directly on the brain or indirectly via effects on the immune system, for example.

And finally, the brain has effects on our gut. For example, it is common to have digestive symptoms (abdominal pain, diarrhea) during a stressful event like an exam or a job interview.

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Here's a quick look at how Prof. Sokol answers this question from his patients

The microbiota plays a special role in the digestion of plant fibers that are present in fruits and vegetables. These fibers are long sugar molecules that our human enzymes are unable to break down into pieces.

They thus arrive intact at the colon where they encounter a large number of bacteria that are capable of digesting them. The bacteria use these fibers for their own needs and release very important molecules for human health, short-chain fatty acids (sidenote: Short chain fatty acids (SCFA) Short chain fatty acids (SCFA) are a source of energy (fuel) for an individual’s cells. They interact with the immune system and are involved in communication between the intestine and the brain. Silva YP, Bernardi A, Frozza RL. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front Endocrinol (Lausanne). 2020;11:25. ) , such as butyrate, for example.

These short-chain fatty acids have multiple effects. Butyrate nourishes the cells of the colon and thus promotes the integrity of the intestinal mucosa (sidenote: De Cruz P, Kamm MA, Hamilton AL, et al. Crohn’s disease management after intestinal resection: a randomised trial. The Lancet. 2015;385(9976):1406–1417 ) . Short-chain fatty acids can modulate the immune response and thus contribute to protection against inflammatory diseases.

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Here's a quick look at how Prof. Sokol answers this question from his patients

First of all, it is completely normal for the digestive tract to produce gas. In general, a healthy person produces between 0.5 and 1.5 liters of gas per day. 

And yes, the gut microbiota plays an important role in this gas production. The microbiota, by fermenting the food residues that reach the colon, will produce different gases, such as hydrogen, carbon dioxide, and even sometimes methane.

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Here's a quick look at how Prof. Sokol answers this question from his patients

Even though we can't see them with the naked eye, microorganisms, like bacteria, are all around us. They are also all over our bodies.

The gut microbiota is the collection of microorganisms (sidenote: Microorganisms Living organisms too small to see with the naked eye. This includes bacteria, viruses, fungi, archaea, protozoa, etc., collectively known as ’microbes’. Source: What is microbiology? Microbiology Society. ) , bacteria, fungi, and viruses, that colonize our digestive tract from birth.

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Here's a quick look at how Prof. Sokol answers this question from his patients

Recent research results indeed suggest that the gut microbiota could play a role in the initiation or severity of several neuropsychiatric disorders such as depression, anxiety, schizophrenia, or autism. 

However, the data available to date remain very preliminary and we do not know what the "weight" of the microbiota is compared to other factors such as genetics or the environment and if all patients are affected. 

Finally, we do not yet know if the microbiota can be targeted therapeutically in these pathologies.

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Here's a quick look at how Prof. Sokol answers this question from his patients

The microbiota acts on the brain through several mechanisms.

• First, there are strong nerve connections between the brain and the gut. These connections go from the brain to the gut,which explains, for example, digestive symptoms in case of stress, but they also go from the gut to the brain. By acting on the intestinal nerve endings, the microbiota can thus modulatebrain function.

• The microbiota also produces chemical molecules that are absorbed enter the bloodstream and can reach the brain and exert effects there.

• Finally, the microbiota can act indirectly on the brain by having effects on other human cells, such as gut cells or immune cells, which, in response, will produce molecules that will act on the brain.

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