Clostridium difficile (also known as Clostridioides difficile or C. diff) is a potentially pathogenic bacterium that can be found in the gut of healthy individuals. In states of optimal health, C. diff is kept in check by friendly gut microbes,1 but disruptions in microbiome balance commonly associated with antibiotic use allows C. diff to proliferate and produce its bacterial toxins. These toxins result in diarrhea with the potential of more significant complications, even including death.2
Considered a leading hospital-associated infectious disease, community-acquired C. diff has been on the rise in the United States in the past several years.3 In addition to causing debilitating gastrointestinal disease, emerging research also indicates that this bacteria produces compounds that negatively influence brain activity.4 In fact, the American Society for Microbiology (ASM) recently published an article,5 which directly links gut microbiome disruption with neurological disease, anxiety in particular.
The relationship between C. diff and anxiety symptoms specifically appears to be linked to the production of a toxic bacterial metabolic byproduct released by C. diff, a metabolite called para-cresol (p-cresol). P-cresol both encourages gut dysbiosis (Harrison, M., 2020) and interferes with the metabolism of dopamine, a feel-good neurotransmitter, into norepinephrine (a.k.a. noradrenaline), a neurotransmitter responsible for alertness and attention. As p-cresol levels rise, dopamine to noradrenaline conversion slows, resulting in increased dopamine and decreased norepinephrine in the brain.6
Unchecked elevations in brain dopamine result in undesirable cognitive symptoms including: anxiety, paranoia, intense excitement, emotional eating, and autistic behaviors.7 While at the same time, low levels of brain noradrenaline have been associated with: low blood pressure (hypotension), low blood sugar (hypoglycemia), anxiety, weakness, and depression.8
Fortunately, research into the mechanisms by which specific gut microbes impact the nervous system has expanded our understanding and opened the door for more integrated approaches to mental health and wellness. As a naturopathic physician specialized in mental health, I rely on organic acid testing to identify the presence of the primary C. diff metabolites responsible for neurological disturbance: HPHPA (3-(3-hydroxyphenyl)-3-hydroxypropionic acid), 4-Hydroxyphenylacetic acid, 3-Indoleacetic acid and 4-Cresol.9 Once detected, I am equipped to target a root cause of anxiety related symptoms in my patients with a three-pronged integrative approach:
1. Gut Microbiome Restoration: Research has suggested that certain strains of probiotic bacteria offer significant therapeutic value in mitigating the effects and symptoms associated with C. diff. infection.
Specific strains of Lactobacillus rhamnosus and Lactobacillus plantarum have been shown to inhibit C. diff. growth and toxin production, repair leaky gut, and reduce related inflammation.10
Two formulation-specific studies also revealed that probiotic therapy led to significant C. diff. symptom remediation11 and resulted in clearance of antibiotic resistant C.diff infection.12
2. Inhibit C. diff Growth: While the oral antibiotics metronidazole and vancomycin tend to be quite effective against C. diff, the trade off is that these antibiotics also kill beneficial gut bacteria.13
Fortunately, clinically studied alternatives are promising. For example, curcuminoids, a constituent of turmeric, are shown to inhibit growth of C. difficile without the detrimental effects of antibiotics.14
3. Eliminate C. diff Spores: Because C. diff can form protective biofilms and maintain a persistent “vegetative” presence in spore form,15 I use complementary approaches to attack the problem. For example, clinical evidence suggests that berberine in combination with vancomycin has a synergistic antimicrobial effect against C. diff.16 Berberine is found in certain herbal remedies such as Hydrastic canadensis (goldenseal), Coptis chinensis (Chinese goldthread), and Rhizoma coptidis.16
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An integrative approach to root cause analysis and holistic therapies fills a much-needed gap in effective mental health care. Well-armed with information regarding the presence of potential pathogens and toxic metabolites, along with an understanding of the mechanistic pathways by which these toxins impact mood and cognition, we can design a personalized treatment regimen to address and remediate the underlying problems like diarrhea and return to wellness.
- Bien J., 2013
- American College of Gastroenterology, 2022
- Fu, Y., 2021
- Vinithakumari, A.A., 2022
- Clostridioides difficile Infection Dysregulates Brain Dopamine Metabolism
- Vinithakumari, A.A., 2022
- Cain, N., 2019
- MedicalNewsToday, 2022
- GreatPlains, 2022
- Jeng, H.S., Yan, T.R, 2022
- Hell, M., 2013
- Zollner-Schwertz., 2020
- GreatPlains, 2022
- Mody, D., et al, 2020
- Hogan, D. A., 2021
- Wultanska, D., et al, 2020
Dr. Nicole Cain is a licensed Naturopathic Doctor with a masters in clinical psychology She has been interviewed as a mental health expert in Forbes, published in Well+Good and in journals such as NDNR, and has been a national speaker for PESI. Dr. Nicole’s mission is to introduce a new paradigm for understanding and treating our mental health. As an anxiety warrior herself, she has a special interest in sharing her experiences with anxiety.