Emerging role of the host microbiome in neuropsychiatric disorders: overview and future directions

Abstract

The human body harbors a diverse ecosystem of microorganisms, including bacteria, viruses, and fungi, collectively known as the microbiota. Current research is increasingly focusing on the potential association between the microbiota and various neuropsychiatric disorders. The microbiota resides in various parts of the body, such as the oral cavity, nasal passages, lungs, gut, skin, bladder, and vagina. The gut microbiota in the gastrointestinal tract has received particular attention due to its high abundance and its potential role in psychiatric and neurodegenerative disorders. However, the microbiota presents in other body tissues, though less abundant, also plays crucial role in immune system and human homeostasis, thus influencing the development and progression of neuropsychiatric disorders. For example, oral microbiota imbalance and associated periodontitis might increase the risk for neuropsychiatric disorders. Additionally, studies using the postmortem brain samples have detected the widespread presence of oral bacteria in the brains of patients with Alzheimer's disease. This article provides an overview of the emerging role of the host microbiota in neuropsychiatric disorders and discusses future directions, such as underlying biological mechanisms, reliable biomarkers associated with the host microbiota, and microbiota-targeted interventions, for research in this field.

Fig. 1. Host microbiota in human body.

The human microbiota resides in the various tissues of the body, including the mouth, nose, gastrointestinal (GI) tract, lung, skin, bladder, and vagina. In the GI trats, the density of microbes in different locations, such as the stomach, duodenum, jejunum, ileum, and colon, has been shown [43]. Part of the figure was designed using resources from Biorender.com.

Fig. 2. Potential interactions among the microbiota in the different organs.

The microbiota in one organ may potentially influence that in another organ. The gut microbiota, which constitutes the majority of the host’s microbiome, plays a central role in affecting health and disease throughout the body. Although there are proposed interactions between the microbiota of different organs, current evidence supporting these interactions remains limited. Dysbiosis in the microbiota across various different tissues may contribute to the incidence of organ-specific diseases. COPD: chronic obstructive pulmonary disease. Part of the figure was designed using resources from Biorender.com.

Fig. 3. Role of oral microbiota in neuropsychiatric disorders.

The oral microbiota consists viruses, bacteria, archaea, fungi, and protozoa. In comparison to a healthy microbiome (eubiosis), patients with periodontitis exhibit an imbalanced microbiome (dysbiosis), which can contribute to the development of neuropsychiatric disorders. Studies utilizing postmortem brain samples have demonstrated the presence of the oral microbiota in the brains from patients with Alzheimer’s disease (AD) or Parkinson’s disease [105]. Part of the figure was designed using resources from Biorender.com.

Fig. 4. Nasal microbiota in the olfactory function.

The nasal cavity can be divided into distinct regions, including the nasal vestibules, respiratory region, olfactory region, and nasopharyngeal region. The nasal microbiota colonizes these regions, and plays a crucial role in maintaining the health of the nasal mucosa and overall immune system function. There are three pathways from the mucus layer to the olfactory bulb: (a) the transcellular pathway, which involves passage through epithelial cells; (b) the paracellular pathway, which occurs between epithelial cells; and (c) the intracellular pathway, which occurs through the olfactory nerve. Considering the crucial role of the nasal microbiota within the nasal cavity, it is plausible that both the nasal microbiota and their metabolites may have a role in neuropsychiatric disorders. Part of the figure was designed using resources from Biorender.com.

Fig. 5. Potential role of vaginal microbiota in the development of neuropsychiatric disorders in offspring following maternal immune activation.

The vaginal microbiota, particularly, the Lactobacillus species, plays several significant roles in maintaining vaginal health. There is an association between the composition of the vaginal microbiota and reproductive health, including the risk for spontaneous preterm birth. Maternal immune activation (MIA), which can result from a range of factors such as infections, immune challenges, stress, environmental exposures, has been linked with an increased risk of neuropsychiatric disorders in offspring. Dysbiosis of the vaginal microbiota due to MIA, along with subsequent disrupted immune responses, may foster the development of neuropsychiatric disorders in offspring. This imbalance in the vaginal microbiota might impact the synthesis of D- and L-lactic acid and other metabolites, leading to changes in pH and the immune system in the vagina. Furthermore, an imbalance in the vaginal microbiota may influence mental health issues in women throughout their lives. Part of the figure was designed using resources from Biorender.com.