FMT and Psychiatric Issues: What We Know Now

My long-time readers may remember my tirade from almost 4 years ago re:  the FDA denying patients the right to use natural treatments like helminths and fecal microbiota transplant (FMT) as they see fit.  I had been (and still am) incensed after reading a 2014 article in a legal journal, “Of Poops and Parasites: Unethical FDA Overregulation.”[i] From that article:  “Thousands of Americans suffer from illnesses untreatable by presently available therapies. And while unapproved treatments may exist and even be known to be efficacious, the FDA persists in making them unavailable (ex. clinical trials are not finished), leaving no choice for the doctor, and no choice for the patient.”  Currently, FMT is only permitted by the FDA for the treatment of Clostridium difficile infection, even if a doctor wants it as an option for treating patients.

That post came to mind this weekend when I read a new review article in BMC Psychiatry on the use of FMT to treat psychiatric disorders. [ii]   It especially hit home because my own son, Alex, who if you’ll remember, is diagnosed with autism, has been suffering horribly with debilitating anxiety the last year.  And in my work teaching nonspeaking individuals with autism how to communicate via spelling, I see daily their suffering from OCD and anxiety.  It breaks my heart.  (You can read more about autism and anxiety here.)

These researchers culled through the medical literature and found 21 clinical studies that met their inclusion criteria.  Spoiler alert – I’m giving you the conclusion first:  there is “strong evidence” that psychiatric illnesses like anxiety and depressive disorders can be treated through this non-invasive method, with negligible side effects.

Here are some highlights from the article:

1. In the background section, the authors point out that the gut bacteria are “…critical in the normal development of the immune system, central nervous system(CNS) circuitry, GI functioning, and autonomic nervous system (ANS) functioning.” (See the second paragraph of this post, re:  Alex and my other students with autism.)  Studies in rodents has clearly demonstrated many times that lack of exposure to normal commensal organisms leads to abnormalities in stress response in adulthood.  That I’ve written about innumerable times on this blog!
2. If you can believe it (and I don’t recall ever reading this before myself), FMT was first ever used in fourth century China to treat food poisoning and diarrhea! So we have essentially 1700 years of empirical data showing efficacy.
3. FMT (which may be delivered via endoscopy, enema or oral feeding of freeze-dried material) has been explored for not only the treatment of gastrointestinal disorders and psychiatric issues, but also for autism (you can read about that here), Parkinson’s disease and multiple sclerosis. The data are still accumulating.
4. The paper breaks down the included studies into three groups: preclinical – animals only, preclinical – human microbiota transferred into animals, and human clinical trials.
5. There were 11 preclinical studies on animals included in this paper. It has been demonstrated that transferring the microbiota of anxious mice to  healthy mice transfers the anxiety issues.  In another study, the microbiota of mice forced into “alcoholism” were transferred to healthy controls, thereby transferring depressive behavior.  Conversely, transferring healthy microbiota into mice with anxiety and other disorders results in the reduction of anxiety and depressive symptoms in the affected animals.
6. 9 studies of human-to-rodents were included. A couple of examples include FMT from people with depression into germ-free mice results in depression-like behaviors in the animals.  As in the animal-to-animal studies, transferring the microbiota from human alcoholics into rodents results in the development of anxiety and depressive behaviors in the mice.  Interestingly, giving “alcoholic” mice transplants from healthy humans had a protective effect on the mice’ behaviors:  they did not develop the normal depression seen in alcohol-dependent mice.  One more interesting one:  FMT from people with anorexia to mice results in the animals developing obsessive and compulsive behaviors.  Amazing, right?
7. 8 human clinical trials made it into the paper, all of which assessed for psychiatric symptoms, some depression, some anxiety, one for neuroticism, and 2 or quality of life related in irritable bowel syndrome, one for fatigue. In the short-term, ALL the papers found improvement in depression symptoms.  The long-term results were more inconsistent though, some finding the effects wore off after 3 months, some found they lasted up to 6 months.  All 4 studies which assessed anxiety found efficacy, although one did not reach statistical significance.  Like anxiety and depression, the other psychiatric issues assessed (i.e. fatigue, neuroticism, etc.) all improved – the only variable being, for how long the effects lasted.

This then seems to be the only issue:  the treatment likely will need to be repeated every 3-6 months.

The exact mechanisms of action are as yet unknown.  Some of the prevailing theories have to do with serotonin production, immune response, short-chain fatty acid production, and bacterial metabolites affecting vagus nerve signaling to the brain.  I won’t be surprised if all these play a role:  time will tell.  What we do know is that it works, it works well, side effects are negligible.  As these authors point out, antidepressant medications are also highly effective but, “…a large proportion of individuals with psychiatric illnesses do not respond to these first-line treatments, and thus need to try alternatives]. Further, many antidepressant users also experience side effects such as restlessness, nausea, vomiting, anxiety, insomnia, sexual dysfunction, gastrointestinal cramps and diarrhea, and headaches that can make the arduous process of searching for effective treatments even harder.”

Thus, they conclude, FMT is a “promising candidate” for treating psychiatric illness.  (Ya think?)  We can only hope that those of us with such issues, or with a loved one suffering, these treatments will soon become available.  If I could treat Alex today, the door would not be hitting me on the way out.

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[i] Young, KA. Of poops and parasites: unethical FDA overregulation. Food and Drug Law Journal. 2014;69(4):555-574.

[ii]  Chinna Meyyappan A, Forth E, Wallace CJK, Milev R. Effect of fecal microbiota transplant on symptoms of psychiatric disorders: a systematic review. BMC Psychiatry. 2020 Jun 15;20(1):299. doi: 10.1186/s12888-020-02654-5. PMID: 32539741; PMCID: PMC7294648.