Clostridia are a group of both good and bad bacteria that normally inhabit the digestive tract of humans. Certain strains of clostridia can be problematic when present in excessive numbers. The most well-known strain is clostridia difficile (or “c. diff”). C. diff infection is frequently acquired in the hospital setting after a course of antibiotics. C. diff can lead to severe unrelenting diarrhea with serious complications such as pseudomembranous colitis.

While working in the hospital setting, c. diff infection was probably the most common infection I encountered among patients I was called to see for psychiatric reasons. Approximately 1 out of every 5 hospitalized patients was dealing with an acute diarrheal illness caused by c. diff. This required me to take special “contact precautions”. I’d have to don a yellow disposable gown, wear gloves, avoid contact with surfaces in the room, and thoroughly wash my hands with soap and water upon leaving the room. These patients were often severely depressed. They felt miserable and weak.¹ Some were delirious, psychotic, and confused.

Milder, subclinical infections with c. diff can occur in healthy appearing people in the community as well. Overgrowth of C. diff and other pathogenic strains of clostridia in the gut can cause psychiatric symptoms in people without any gastrointestinal symptoms.

Pathogenic strains of clostridia are known to release a toxic metabolite called HPHPA. HPHPA in the gut, gets absorbed into the systemic circulation, and enters the brain where it blocks the function of an enzyme called dopamine beta hydroxylase.² This causes excessive levels of dopamine to build up in the brain, which can lead to a variety of psychiatric symptoms and behavioral problems.³

It is not surprising that the rate of C. diff infection is known to be significantly greater among people who reported feeling sad, depressed, nervous, or any psychiatric problem. ⁴ I suspect that the presence of mood problems is an early sign of asymptomatic overgrowth of c. diff and serve as a harbinger for those at risk of full blown c. diff infection.

Functional medicine practitioners use a specialty test called the organic acids test to measure levels of HPHPA in the urine. Approximately one out of five people will show elevated levels of HPHPA.

People with elevated HPHPA from clostridia overgrowth usually don’t feel well mentally. Many have had poor reactions to psychiatric medications in the past because the root cause of their symptoms were not being addressed. For these cases, functional medicine practitioners have observed that treatment with antimicrobials and high dose probiotics lowers HPHPA levels and lead to noticeable improvement of psychiatric symptoms.

References

1.         Armstrong EP, Malone DC, Franic DM, Pham SV, Gratie D, Amin A. Patient Experiences with Clostridioides difficile Infection and Its Treatment: A Systematic Literature Review. Infect Dis Ther. 2023;12(7):1775-1795. doi:10.1007/s40121-023-00833-x

2.         Vinithakumari AA, Padhi P, Hernandez B, et al. Clostridioides difficile Infection Dysregulates Brain Dopamine Metabolism. Microbiology Spectrum. 2022;10(2):e00073-22. doi:10.1128/spectrum.00073-22

3.         William Shaw (2010) Increased urinary excretion of a 3-(3-hydroxyphenyl)-3hydroxypropionic acid (HPHPA), an abnormal phenylalanine metabolite of Clostridia spp. in the gastrointestinal tract, in urine samples from patients with autism and schizophrenia, Nutritional Neuroscience, 13:3, 135-143, DOI: 10.1179/147683010X12611460763968

4.         Rogers MA, Greene MT, Young VB, et al. Depression, antidepressant medications, and risk of Clostridium difficile infection. BMC Medicine. 2013;11(1):121. doi:10.1186/1741-7015-11-121

Medical Disclaimer: The information mentioned in this article is not intended to diagnose, treat, cure, or prevent any disease. The information provided is for educational purposes only and is not intended to replace the relationships with your medical provider(s). Before initiating any treatment, please first consult with your licensed medical provider.