In a recent study published in Molecular Psychiatry, scientists reviewed existing literature to understand how the microbiome influences neuropsychiatric disorders. More specifically, they explore the underlying mechanisms and highlight reliable biomarkers that could be used to formulate microbiota-targeted interventions to treat people with neuropsychiatric disorders.
Study: Emerging role of the host microbiome in neuropsychiatric disorders: Overview and future directions. Image Credit: sruilk / Shutterstock.com
Human neuropsychiatric disorders
The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) indicated that neuropsychiatric disorders remain a top global health issue with no signs of reduction since 1990.
Some common neuropsychiatric disorders that are globally prevalent include bipolar disorder (BD), schizophrenia, major depressive disorder (MDD), autism spectrum disorder (ASD), substance use disorder, and anxiety disorders. These disorders not only have a tremendous impact on the patient but their family members as well.
The prevalence of anxiety disorders and MDD have significantly increased due to the coronavirus disease 2019 (COVID-19) pandemic. Both genetic and environmental factors influence the development and manifestations of neuropsychiatric disorders. To date, few studies have discussed the biological mechanisms linked to the development and progression of these disorders.
Homeostasis in the body is regulated by a bidirectional network that constitutes brain-body crosstalk. Some of the key components of this crosstalk are neurotransmitters, the central nervous system (CNS), feedback loops, the peripheral nervous system, chemical signaling, hormones, and homeostasis.
It is important to understand the underlying mechanisms related to the brain-body crosstalk that influence the pathogenesis of neuropsychiatric disorders.
The impact of host microbiota on neuropsychiatric disorders
Host microbiota has an important role in maintaining overall health. Notably, there are various types of microbiota, including those found within the mouth, nose, skin, gut, lungs, vagina, and bladder, each of which comprises highly complex microbial communities.
The microbiota of a specific organ can easily influence other organs. For example, the gut microbiome influences multiple organs and is associated with the overall health of an individual.
The diversity and composition of the gastrointestinal (GI) microbiota varies throughout the stomach, jejunum, duodenum, ileum, and colon. The gut microbiota-brain axis promotes bidirectional communications between the brain and gut microbiota in the GI tract.
Gut microbiota can regulate brain functions and behavior through various mechanisms. For example, gut microbes produce many neurotransmitters, some of which include dopamine, kynurenic acid, γ-aminobutyric acid (GABA), and serotonin, as well as metabolites like bile acids, short-chain fatty acids (SCFAs), and D-amino acids, that can regulate brain function and behavior.
Previous studies have shown that as compared to healthy people, patients with Alzheimer’s disease (AD) have reduced levels of D-glutamate. Notably, plasma levels of D-glutamate have been directly correlated with cognitive functions. The presence of D-glutamate as a key component of the peptidoglycan cell wall in bacteria indicates the possible opportunity for gut microbiota to produce this metabolite.
Altered gut microbial composition and diversity influence the manifestation of schizophrenia, anxiety, BD, MDD, Parkinson’s disease (PD), and AD. For example, a reduction in anti-inflammatory butyrate-producing bacteria such as Faecalibacterium and Coprococcus and an increase in pro-inflammatory bacteria like Eggerthella have been observed across various psychiatric disorders including MDD, schizophrenia, BD, and anxiety.
The key entry routes of potential pathogens through which they spread in the CNS are oral and nasal cavities. Oral microbiota represents the second largest microbial community in the human body, with its key phyla including Bacteroidetes, Firmicutes, Actionobacteria, Fusobacteria, and Proteobacteria.
Interestingly, patients with psychiatric disorders often exhibit poor oral hygiene and a higher prevalence of dental decay. Previous studies have shown that periodontitis could influence the development of neuropsychiatric disorders. In fact, one case-control study revealed that as compared to controls, BD patients had a higher prevalence of periodontitis and elevated levels of Aggregatibacter actinomycetemcomitans, and Porphyromonas gingivalis.
The nasal cavity harbors diverse microorganisms with a predominance of Actionobacteria, Firmicutes, and Proteobacteria. An imbalance in nasal microbiota has been linked with many health conditions.
Nasal microbiota influences the gut microbiota-brain axis through the olfactory system, immune system modulation, and production of neurotransmitters or metabolites that can penetrate the blood-brain barrier. Nasopharyngeal microbiota dysbiosis induces inflammatory responses to α-synuclein that cause pathological changes in PD.
The major phyla that comprise the lung microbiota include Firmicutes, Bacteroidetes, and Proteobacteria. Lung microbial diversity is directly related to environmental exposure, immune function, host genetics, and lifestyle.
Based on the function of lung microorganisms in local pulmonary immune homeostasis, it is clear that these microbes influence systemic humoral factors. Nevertheless, additional studies are needed to elucidate the role of the lung microbiota in the development and progression of neuropsychiatric disorders.
Millions of microorganisms are present in human skin, which is the largest organ of the body. The most dominant phyla present on human skin are Firmicutes, Actionobacteria, Bacteroidetes, and Proteobacteria.
Skin microbiota provides a protective role against pathogenic infestation. Microbial composition varies significantly across different skin regions, such as the glabella, volar forearm, antecubital fossa, sebaceous, and web space.
Notably, one previous study revealed that alterations in the skin microbiota lead to anorexia nervosa.
Bladder and vaginal microbiota
The composition and diversity of bladder or urinary microbiota are distinct from the skin or gut microbiome; however, both vaginal and bladder microbiota exhibit similar composition. To date, no studies have reported a role of the bladder microbiota in the manifestation of neuropsychiatric disorders; however, one study revealed that patients with BD had a higher concentration of certain metabolites that could be contributed by bladder microbiota.
The vaginal microbiome has a significant number of Lactobacillus species that protect the vagina from infection. Previous studies have shown that the vaginal microbiota is associated with the prevalence of human papillomavirus (HPV). Women infected with HPV are at a higher risk of depression, eating disorders, premenstrual dysphoric disorder, and anxiety.
- Hashimoto, K. (2023). Emerging role of the host microbiome in neuropsychiatric disorders: Overview and future directions. Molecular Psychiatry; 1-13. doi:10.1038/s41380-023-02287-6