The intercommunication between the central nervous system and the digestive system and its contribution to mental health status

In a recent study published in the Frontiers in Medicine, researchers presented a comprehensive analysis of the correlation between gut microbiota and neurological as well as psychiatric disorders.

Background

In the past decade, there has been an increasing focus on exploring the correlation between the brain, gut microbiota, and neurological disorders. Numerous clinical and preclinical research studies have emphasized the potential of gut microbiota to regulate overall health status. It is evident that gut microbiota significantly influences neurogenesis, cognitive and mental development, emotions, behaviors, and the development of neuropsychiatric illnesses.

The relationship between gut microbiota and neuropsychiatric status

The health and neuropsychiatric condition of an individual can be influenced by both internal and external factors, including lifestyle choices, dietary patterns, and medication usage. Lifestyle habits have a significant impact on the interplay between gut microbiota and the brain and are considered one of the contributing factors to the multifactorial etiology of psychiatric disorders, alongside genetics, inflammation, and neurotransmitter dysregulation.

Dietary factors play a critical role in promoting overall health and well-being. The inherent human feeding pattern is subject to the influence of cultural, religious, and societal factors. The consumption of a high-fat diet (HFD), which primarily consists of saturated and/or trans fats, has been found to alter the composition of the microbiota.

Antibiotics are a commonly utilized class of medication for treating various ailments in the realm of pharmaceutical consumption. The consumption of antibiotics significantly impacts the structure and operation of the intestinal microbiota by disturbing the balance among mutually beneficial populations, resulting in persistent detrimental consequences for the host. The antibiotic administration in high doses or for prolonged periods can result in significant alterations or irreversible damage to both the brain and intestinal levels.

Neurological disorders and alterations in microbiota

Depression

Major depressive disorder (MDD) is primarily influenced by environmental, biological, and genetic factors, which interact in complex ways to contribute to the onset and maintenance of the disorder.

Currently, MDD is commonly managed through the administration of antidepressants. These medications work by increasing the densities of neurotransmitters in the synaptic cleft and inhibiting the corresponding brain transporters, such as serotonin and norepinephrine. The transporters and receptors implicated in depression have been identified in the gastrointestinal tract, which is closely interconnected or modulated by the gut microbiota.

Based on recent research, it is recommended that the host microbiome be given significant attention in developing novel psychotropic drugs for managing mental disorders. This is because various antidepressant medications possess antimicrobial properties against representative strains found in the human gut microbiota, particularly Akkermansia muciniphila, Bacteroides fragilis, and Bifidobacterium animalis.

Anxiety

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Anxiety disorders are a commonly occurring phenomenon among the adult population, with generalized anxiety disorder (GAD) being one of the most prevalent and persistent forms of diagnosis. The malfunction of the amygdala in anxiety-inducing situations, specifically in the context of the hypothalamic-pituitary-adrenal (HPA) axis, shares a similar susceptibility to environmental stressors as the gut microbiota throughout an individual's lifespan.

The onset of various psychiatric disorders is associated with the intersection of dysfunctions in both the amygdala and microbiota. The gastrointestinal tract inflammation prompts the release of cytokines that are pro-inflammatory in nature. The escalation of tumor necrosis factor (TNF)-α and interleukin 6 (IL-6) cytokines is directly associated with the manifestation of anxiety-like symptoms.

Serotonin plays a crucial role in the functioning of the gastrointestinal system and the connection between the gut and the brain. Additionally, it serves as a neurotransmitter that is integral to cognitive processes and mood regulation. Studies indicate a higher prevalence of Bacteroides in the microbiota of individuals with anxiety-like disorders than those who are healthy. The study revealed a reduced prevalence of bacteria that produce short-chain fatty acids (SCFAs) among individuals diagnosed with GAD.

Bipolar disorder

Bipolar disorder is a complex and chronic neuropsychiatric condition characterized by recurrent episodes of mania and depression. The key factors contributing to this phenomenon include significant modifications in brain function, underlying pathophysiological mechanisms, the impact of nitrosative and oxidative stress, neurotrophin and calcium signaling pathways, and alterations in cellular bioenergetics. BD patients exhibit heightened bacterial translocation markers that originate from the intestinal lumen, which may contribute to the increased inflammation observed in these individuals when compared to their healthy counterparts.

Autism

The severity of autism is closely linked to the gut microbiota, which is considered among the most significant contributing factors. The modification of gut microbiota caused by medication, antibiotic treatments, or insufficient nourishment is strongly associated with atypical emotional behavior and neurological dysfunction, which can lead to the onset of Autism Spectrum Disorder (ASD).

The etiology of ASD is associated with a modification in the metabolic process of an essential aromatic amino acid called tryptophan. This alteration is triggered by modifications in the composition of the gastrointestinal microbiota.

Conclusion

The bidirectional interaction between the brain and the gut via the microbiome-gut-brain axis has been identified as a contributing factor in the pathogenesis of prevalent neurodegenerative disorders, including but not limited to anxiety, depression, autism, and bipolar disorder.

The researchers believe that it is imperative to prioritize research efforts toward investigating the effects of psychobiotics on health outcomes with respect to variables such as patients' age range, health conditions, and genetic makeup. Additionally, it is essential to explore the efficacy of both single- and multi-probiotic formulations, as well as the optimal dosage and timing of administration.

Written by

Bhavana Kunkalikar

Bhavana Kunkalikar is a medical writer based in Goa, India. Her academic background is in Pharmaceutical sciences and she holds a Bachelor's degree in Pharmacy. Her educational background allowed her to foster an interest in anatomical and physiological sciences. Her college project work based on ‘The manifestations and causes of sickle cell anemia’ formed the stepping stone to a life-long fascination with human pathophysiology.