©Kateryna Kon
The microbiome
Microbes can also interact with each other within the gastrointestinal tract and other mucosal sites. This combination of microbes within the gastrointestinal tract has been characterized as the microbiome. Each person’s microbiome is established in early life and is determined by genetic and environmental factors. Environmental factors that shape the microbiome include exposure to microbial agents through breast feeding and household contacts, exposure to viruses and other agents that infect the gastrointestinal tract, exposure to allergens and diet.
The microbiome can also be altered by antibiotics and other pharmacological agents including many medications that are used to treat psychiatric disorders. Numerous studies have documented altered microbial composition in samples from individuals with a range of psychiatric disorders including schizophrenia, recent onset psychosis, bipolar disorder, and autism.
The microbiome can also affect the metabolism and pharmacokinetics of orally administered therapeutic agents. Person to person differences in the microbiome might thus explain some of the individual variation noted in the response to orally administered psychotherapeutic agents.
Another intriguing aspect of the microbiome is that is can be manipulated therapeutically by low-toxicity modalities. One type of intervention involves the administration of non-pathogenic microorganisms that can colonize the gastrointestinal tract, generally termed probiotics. Another intervention involves the administration of substances, generally non-digestible sugars called oligosaccharides that are nutrients for non-pathogenic bacteria in the diet and hence can indirectly alter the microbiome. Such prebiotics can also be combined with probiotics to generate what has been characterized as synbioti preparations.
The potential role of probiotic agents in psychiatric disorders is evidenced by some recent research. One study documented that the administration of a probiotic preparation administered with standard medications prevented relapse in individuals discharged after hospitalization for acute mania.8 Another study showed that a similar probiotic preparation improved gastrointestinal symptoms and decreased markers of inflammation in individuals with schizophrenia, although psychiatric symptoms were not significantly altered.9
Dr Yolken is Theodore and Vada Stanley Distinguished Professor of Neurovirology in Pediatrics, Johns Hopkins University, Baltimore, MD; Ms Shwartz is a Psychiatric-Mental Health Nurse Practitioner, Telecare Corporation, Alameda County, CA; and Dr Quanbeck is Associate Medical Director, Cordilleras Mental Health Rehabilitation Center, San Mateo County Health, Redwood City, CA.
1. Bakhshi K, Chance SA. The neuropathology of schizophrenia: a selective review of past studies and emerging themes in brain structure and cytoarchitecture. Neurosci. 2015;303:82-102.
2. Severance EG, Xiao J, Jones-Brando L, et al.Toxoplasma gondii-A gastrointestinal pathogen associated with human brain diseases. Int Rev Neurobiol. 2016;131:143-163.
3. Khandaker GM, Cousins L, Deakin J, et al. Inflammation and immunity in schizophrenia: implications for pathophysiology and treatment. Lancet Psychiatry. 2015;2:258-270.
4. Müller N. Immunological aspects of the treatment of depression and schizophrenia. Dial Clin Neurosci. 2017;19:55-63.
5. Tronel C, Largeau B, Santiago Ribeiro MJ, et al. Molecular targets for PET imaging of activated microglia: the current situation and future expectations. Int J Mol Sci. 2017;18:802.
6. Tay TL, Béchade C, D’Andrea I, et al. Microglia gone rogue: impacts on psychiatric disorders across the lifespan. Front Mol Neurosci. 2017;10:421.
7. Wang AW, Avramopoulos D, Lori A, et al. Genome-wide association study in two populations to determine genetic variants associated with Toxoplasma gondii infection and relationship to schizophrenia risk. Prog Neuropsychopharmacol Biol Psychiatry. 2019;8;92:133-147.
8. Dickerson F, Adamos M, Katsafanas E, et al. Adjunctive probiotic microorganisms to prevent rehospitalization in patients with acute mania: a randomized controlled trial. Bipolar Disord. 2018;20:614-621.
9. Dickerson FB, Stallings C, Origoni A, et al. Effect of probiotic supplementation on schizophrenia symptoms and association with gastrointestinal functioning: a randomized, placebo-controlled trial. Prim Care Companion CNS Disord. February 2014;16 [Epub].
10. Köhler-Forsberg O, Petersen L, Gasse C, et al. A nationwide study in Denmark of the association between treated infections and the subsequent risk of treated mental disorders in children and adolescents. JAMA Psychiatry. 2019;76:271-279.
