Psychobiotics: A paradigm shift in psychopharmacology

Sir,

Psychobiotics have opened up an exciting new arena of translational research in psychopharmacology. This research can bridge the gap between benches to the bedside and in turn, can improve patient outcomes. Psychobiotics was defined by Dinan et al. as live organisms that when ingested in adequate amounts cause health benefits in patients suffering from psychiatric disorders.[1] These are a class of probiotics which often produce essential neurotransmitters such as gamma-aminobutyric acid (GABA), and serotonin, decrease hypothalamopituitary adrenal axis over activity and have anti-inflammatory effects which are beneficial in a range of neuropsychiatric disorders.

The human gut harbors around 10¹⁴-10¹⁵ microbes which is 10 times the number of cells in the human body. These commensal microbes mostly consisting of anaerobic bacteria secrete neurochemicals such as short chain fatty acids, neurotransmitters, and essential amino acids like tryptophan. Bacteria such as lactobacilli and Bifidobacterium secrete essential neurotransmitters like GABA and serotonin whereas Bacillus synthesizes norepinephrine and acetylcholine. The gut microbiota is often called an endocrine organ owing to its regulatory effect on behavioral, emotional and cognitive functioning of human brain.[2] There is a bidirectional communication between the gut microbiota and the brain maintained by endocrine and neurocrine mechanisms; the brain can influence the microbiota composition while the intestinal microbiota can influence brain neurotransmitter levels with consequent effects on emotions, behavior, and pain.

The symbiosis between the gut and the brain in humans is established in prenatal life and maternal microbiota start habituating fetal bodies even before parturition. The process of birth and breast feeding further establishes the gut microbiota of the infant and stabilization of gut microbiota continues till 3 years of age. This stable establishment of gut microbiota is now known to influence neurodevelopment.[3] Preclinical studies on rodents have started showing promising inroads in our understanding of neurodevelopmental disorders such as autism and neurodegerative disorders like Parkinson's disease and schizophrenia.[4]

Animal models of stress-induced behaviors have validated the bidirectional relationship between gut microbiota and stress. Studies carried out in germ-free mice, animals exposed to pathogens and probiotics and antibiotics have provided rich insight into this relationship. The exaggerated stress response in germ-free mice is attenuated with intestinal inoculation of probiotic agents. Stress created by maternal separation, heat or overcrowding is associated with change in gut microbiota composition in infant mice which can be reversed with inoculation with microbiota from healthy mice. Administration of pathogenic bacteria like Campylobacter induces anxiety-like behavior in mice whereas probiotics like Bifidobacterium and Lactobacillus helveticus reduce anxiety-like behavior. Lactobacillus rhamnosus and Lactobacillus helveticus improve memory impairment due to anxiety and Bacteroides fragilis improve anxiety and stereotypical behavior related to autism in mice.[3]

Preliminary results of therapeutic benefits of psychobiotics in human studies are also encouraging: More so in functional disorders such as irritable bowel syndrome and chronic fatigue syndrome. Placebo controlled trials have shown beneficial effects of Lactobacillus infantis in symptoms of irritable bowel syndrome. Both emotional distress and abdominal symptoms had shown response to Lactobacillus. In healthy volunteers, psychological distress was significantly improved with Lactobacillus helveticum and Bacillus longum in a double-blind placebo controlled study.[5] Psychobiotics have also demonstrated their effect in reducing anxiety and depression seen in healthy adult population.[1]

Psychobiotics have heralded a new era in psychopharmacology with their broad spectrum of action which is far more than the mechanism of action of conventional psychotropics. Their potential to act as adjuvants can reduce doses of psychotropics with consequent improvement in efficacy and safety. Psychobiotics with known benefits in preclinical samples need to be tested by randomized placebo controlled trials in clinical population of depressive disorders, anxiety disorders, and stress related disorders to establish their efficacy and safety.[4] In addition, their preventive actions in various stress related psychiatric disorders need to be tested in general population with obvious health benefits.

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Conflicts of Interest

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