Human Gut Microbiota and Mental Health: Advancements and Challenges in Microbe-Based Therapeutic Interventions

Abstract

Gut microbes play prime role in human health and have shown to exert their influence on various physiological responses including neurological functions. Growing evidences in recent years have indicated a key role of gut microbiota in contributing to mental health. The connection between gut and brain is modulated by microbes via neural, neuroendocrinal and metabolic pathways that are mediated through various neurotransmitters and their precursors, hormones, cytokines and bioactive metabolites. Impaired functioning of this connection can lead to manifestation of mental disorders. Around 1 billion of the world population is reported to suffer from emotional, psychological and neurological imbalances, substance use disorders and cognitive, psychosocial and intellectual disabilities. Thus, it becomes imperative to understand the role of gut microbes in mental disorders. Since variations occur in the conditions associated with different mental disorders and some of them have overlapping symptoms, it becomes important to have a holistic understanding of gut dysbiosis in these disorders. In this review, we consolidate the recent data on alterations in the gut microbes and its consequences in various neurological, psychological and neurodegenerative disorders. Further, considering these evidences, several studies have been undertaken to specifically target the gut microbiota through different therapeutic interventions including administration of live microbes (psychobiotics) to treat mental health disorders and/or their symptoms. We review these studies and propose that an integrative and personalized approach, where combinations of microbe-based therapeutic interventions to modulate gut microbes and in-use psychological treatment practices can be integrated and based on patient's gut microbiome can be potentially adopted for effective treatment of the mental disorders.

Keywords: Gut microbiota; Mental health; Microbiota-gut-brain axis; Neurological disorders; Psychobiotics.

Fig. 1

Microbiota and the gut-brain axis. The gut-brain axis forms a bidirectional network involving three major pathways—the neural pathway (vagus nerve, enteric nervous system), the immune pathway (cytokines) and the endocrine pathway (HPA axis, gut hormones). Gut microbiota modulates this axis via numerous direct and indirect ways (1–6, as described in the text). HPA hypothalamic–pituitary–adrenal axis, EE enteroendocrine cells, DC dendritic cells, TJ tight junctions, SCFAs short chain fatty acids. Bold arrows: local interactions; dashed arrows: via circulation

Fig. 2

Gut microbiota in mental disorders. Gut dysbiosis leads to the manifestation of several mental health disorders such as autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), obsessive–compulsive disorder (OCD), depression, bipolar disorder (BD), eating disorders, schizophrenia (SCZ), dementia, Alzheimer’s disease (AD), Parkinson’s disease (PD) and post-traumatic stress disorder (PTSD). Many interventional strategies targeted at restoring healthy gut microbiota through alterations in diet, probiotics, prebiotics, antibiotics and fecal microbial transplants have been suggested as potential therapeutics for these mental disorders

Fig. 3

Burden share of various mental disorders in India [24]