Dual studies offer incredible insights into connection between depression and the gut
Twonewly published studies build on a compelling growing bodyof evidence linking depression with mechanisms in our gut. Afascinating study led by researchers at the Columbia UniversityIrving Medical Center found that low levelsof serotonin, a neurotransmitter associated with depression, candirectly result in gastrointestinal distress such as constipation, while a second study, from the Children's Hospital of Philadelphia,discovered that transplanting gut bacteria from a mouse withdepressive behavior to a healthy mouse, can also result in thetransfer of those depressive behaviors.
Inside our gastrointestinal tract is a massive mesh of neurons.It's the largest collection of neurons found in the body outside ofthe brain, and because of its ability to operate entirelyindependently it has often been referred to as our "second brain." These gut neurons are thought to produce up to 90percent of the serotonin used in the body.
Gastrointestinal disorders are commonly reported by patientssuffering major depression. While we know that low levels ofserotonin can affect a person's mental health, it is unclearwhether this important neurotransmitter also plays a role in ourdigestive system. A new study suggests low serotonin levelscould be causing both gut and brain disorders.
"The gut is often called the body's 'second brain,'"says study leader Kara Gross Margolis. "It contains more neuronsthan the spinal cord and uses many of the same neurotransmitters asthe brain. So it shouldn't be surprising that the two conditionscould be caused by the same process."
To study this connection between serotonin and the gut,researchers examined a mouse model engineered with a genetic mutation that results in major depression by impairing serotonin production. It was discovered depleting serotonin production causednotable disruptions to the animal's gastrointestinal tract,including a reduction in gut neurons and a slowing in the movement ofcontents through the gut.
"Basically, the mice were constipated and they showed thesame kind of GI changes we see in people with constipation," saysMargolis.
Even more importantly, it was revealed that a new experimentaltreatment, originally developed to target depression, also worked toraise serotonin levels in the gut and improve constipation symptoms.The drug is a new slow-release formulation of 5-HTP, a precursormolecule that is converted into serotonin when ingested.
This intriguing connection between depression and the gut has alsobeen affirmed in a different study, recently published in thejournal Molecular Psychiatry. This research set out to examinewhether microbiome changes in the gut could alter an animal'smental health. Compelling prior work has found interestingassociations between certain species of gut bacteria and major depression. In fact, one strange study from earlier this yearsuggested symptoms of schizophrenia could be transferred from oneanimal to another simply through a fecal transplant.
In a collaboration between the PerelmanSchool of Medicine at the University of Pennsylvaniaand the Children's Hospital of Philadelphia, the new study exploredhow chronic exposure to stress can alter an animal's microbiome,causing depressive behavior, and how these behavioralcharacteristics can then be transferred to healthy animals via a microbiometransplant.
"In rats that show depressive-type behavior in a laboratorytest, we found that stress changes their gut microbiome – thepopulation of bacteria in the gut," explains study leader SeemaBhatnagar, from the Children's Hospital of Philadelphia. "Moreover,when we transplanted bacteria from those stress-vulnerable rats intorats that had not been stressed, the recipient animals showed similarbehavior."
This study also found that brain inflammation increased in thehealthy animals following the transplantation of a microbiome from astressed donor. This suggests certain gut bacteria has the ability tomodulate inflammatory reactions in the brain.
Interestingly, it was observed that the microbiome transplants onlyinduced depressive-type behaviors in the recipients and notanxiety-type behaviors. The researchers hypothesize this result points toward a mechanistic distinction between the causes ofdepression and the causes of anxiety, and that depression may be moreinfluenced by gut bacteria.
"Although much more research remains to be done, we canenvision future applications in which we could leverage knowledge ofmicrobiome-brain interactions to treat human psychiatric disorders,"says Bhatnagar.
While both studies are still only proven in animals, there areplans to move forward with human trials for the serotonin research, exploring whether the new 5-HTP formulation effectively treats both depression and constipation.It's early days, and much more work is needed before thesediscoveries are translated into clinical treatments, however, thegrowing consensus seems to be that mental health issues such asdepression may not be just in your head, and the second brain in yourgut may play a big role in future treatments.
The serotonin/5-HTP study was published in the journalGastroenterology.
The microbiome transplant study was published in the journalMolecular Psychiatry.