Obsessive-compulsive disorder (OCD) is a debilitating condition characterized by recurring, unwanted thoughts and ideas (obsessions) and behaviors (compulsions). Treatment strategies often fall short.

A new direction has emerged in that expanding evidence suggests brain development and function is linked to the gut microbiome. Along with conveying potential biomarkers, the gut microbiome may offer a modifiable factor—by the use of probiotics, for instance—involved in the development or progression of OCD.

 

OCD, in brief

The prevalence of OCD is not established, though is estimated to be about 1 to 2%.

A preponderance of evidence supports a combined treatment with selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral approaches. Most patients show some symptom improvement with these interventions, either alone or in combination. However, 40-60% of OCD patients exhibit disabling residual symptoms.

New therapeutic options are needed.

Notably, most neuropsychiatric disorders are considered as multifactorial disorders prompted by certain environmental factors in genetically susceptible individuals. The gut microbiota may play a key role.

 

Microbiome gut-brain axis

Communication between the gut-microbiota and the brain is bi-directional as well as multi-faceted. Neural, hormonal, immune and metabolic pathways have been suggested. Various studies report that gut microbiota can shape brain physiology and thus behavior through the gut-microbiota-brain axis, pointing to gut microbiota as a possible trigger factor in the development of many neuropsychiatric conditions. This table illustrates preclinical evidences of the role of gut microbiota on behavior.

Gut microbiota may:

• Produce or consume a wide range of neurotransmitters including dopamine, norepinephrine, serotonin, or gamma-aminobutyric acid (GABA).
• Produce short chain fatty acids (SCFAs) which may regulate microglial activities.
• Produce SCFAs that may regulate histone deacetylases and thereby reduce inflammation.
• Help normalize the hypothalamic-pituitary-adrenal (HPA) axis when it is activated by stress. Neuroinflammation via cytokine and chemokine production is a hallmark of many mental health conditions.
• Modulate both gut barrier and blood-brain barrier permeability associated with bacterial infiltration and inflammatory responses
• Increase brain-derived neurotrophic factor (BDNF), a key molecule in neuron health.

Interestingly, researchers have noted that phases of more instability in the composition of gut microbiome—perinatal, adolescent, and old age—overlap with the windows of greater vulnerability in brain development.

OCD and the gut microbiome

Direct links between OCD and the gut microbiome are lacking. However, the numerous neural, hormonal, metabolic, and immune pathways discovered along the gut-brain axis offer compelling reasons to investigate these interactions in OCD.

For example, researchers hypothesize that immune dysregulation may contribute to the onset of OCD, perhaps similar to what happens in post-streptococcal autoimmune disease. Some patients with OCD exhibit changes in circulating cytokines and immune cells. As mediators of inflammation, cytokines alter neurotransmitter concentrations implicated in pathogenesis of OCD. Moreover, a recent study showed presence of microglial activation throughout all neurocircuitry of OCD including those regions that control movement execution, habit formation, and reward.

As described before, gut microbiota influences many processes involved in brain development and function. Evidence linking microbiome and other neurodevelopmental disorders such as autism and attention deficit disorder suggests fertile ground for study involving the application of “psychobiotics” in OCD.

 

Probiotics in OCD

Animal studies:

A strain of Lactobacillus casei was beneficial in the treatment of OCD in a rat model, possibly exerted through the modulation of serotonin-related genes expression.

In addition, two experiments looked at pretreatment with a popular strain of Lactobacillus rhamnosus on an OCD-induced mouse model. Both a two and four-week probiotic pretreatment attenuated OCD-like behavior relative to saline pretreatment. In the second experiment, Lactobacillus rhamnosus treatment appeared comparable to fluoxetine treatment in reducing mouse OCD-like behaviors.

Human studies:

In a case study, treatment with Saccharomyces boulardii successfully reduced OCD symptoms in a boy with autism spectrum disorder.

 

Prebiotics

Research also indicates a beneficial role for prebiotics in management of stress-related behaviors. Specific trials should be done in OCD to explore their potential.

 

Takeaway

More effective treatments for OCD are sorely needed. The gut microbiome may one day prove to be a modifiable target in which probiotics—both affordable and safe—intervene in this devastating disorder. Though meager, preliminary research is promising.

 

Key references:

Burchi, Elisabetta, and Stefano Pallanti. “Diagnostic Issues in Early-Onset Obsessive-Compulsive Disorder and their Treatment Implications.” Current neuropharmacology vol. 17, 8 (2019): 672-680. doi:10.2174/1570159X16666180426151746

Tyler Halverson & Kannayiram Alagiakrishnan (2020) “Gut microbes in neurocognitive and mental health disorders.” Annals of Medicine, 52:8, 423-443, DOI: 10.1080/07853890.2020.1808239

 

Clare Fleishman RDN, MS is a Registered Dietitian with the Academy of Nutrition and Dietetics and holds a master degree in nutrition science. She bridges the gap between science and health across most platforms: major newspapers, magazines, books (Globesity), workshops, social media and websites. From corporate whiteboards to refugee schools in Egypt, Fleishman agitates for personal and public change. In 2010, she launched www.ProbioticsNow.com to share the cascade of new discovery in the microbiome. Always amazed at this “forgotten organ” Fleishman also creates white papers, blogs, videos and social media for the International Probiotics Association as well as continuing education platforms.