Is microbiota manipulation a new therapy for psychiatric diseases?

The gut-brain axis (GBA)

The GBA describes the complex bi-directional relationship between the gut microbiome and intestinal epithelium and the central nervous system, with each influencing the condition and functionality of the other¹. Mechanisms may include immune and inflammatory mediators, neurotransmitter and neuropeptide release, and microbial by-products.

The gut-brain axis may influence behaviors, cognition and emotions

Potential effects of the GBA on physiology and pathophysiology include influencing behaviors, cognition, and emotions, with consequent interest in manipulating the gut microbiome for therapeutic purposes². Multiple factors influence an individual’s gut microbiome, from mode of delivery to genetic variables and diet. Probiotics are foods or supplements containing live microbiota.

Gut microbiota in psychiatry

Gut microbiota may have a role in a wide range of psychiatric disorders including depression, anxiety disorders and schizophrenia¹. Decreased fecal microbial richness is seen in a depression model in rats and patients with depression³. When normal rats were given a humanized microbiota from depressed patients they developed a depressive phenotype³.

Gut microbiota may have a role in a wide range of psychiatric disorders including depression, anxiety disorders and schizophrenia

Alterations in microbiota diversity and complexity, compared to healthy controls, have also been shown in schizophrenia, autism, attention deficit disorder, and mood disorders, including bipolar disorder and anxiety¹. It is still to be determined whether these changes are causal, or an appropriate response to the disease state.

Manipulating the gut microbiota to treat psychiatric conditions

Several meta-analyses support using probiotics to improve mood in patients with depressive symptoms^2,5. A systematic review of three randomized controlled trials (RCTs) found no significant difference in schizophrenia symptoms between probiotic and placebo groups⁴. In bipolar disorder, two clinical trials have demonstrated a beneficial effect of adjunctive probiotics, but intervention studies have mostly been inconclusive². Studies have mainly examined the effect of probiotics on anxiety symptoms in other psychiatric conditions², but one small RCT in patients with diagnosed anxiety disorder did show encouraging results⁶.

Preliminary studies indicate that probiotics are a potential adjuvant treatment for some psychiatric conditions

Systemic reviews, of probiotic use in various psychiatric conditions, have concluded that most of the studies to date have small sample sizes, short study durations, and are heterogeneous in microbiota strains, combinations and doses used, and disease severity^2,4,5,. Larger studies are required, to elucidate whether the perceived efficacy can be replicated in larger populations, and effects maintained for longer periods and when treatment ceases⁵.

Interaction between drugs and the gut microbiome

Pharmacomicrobiomics is an emerging field, investigating interactions between drugs and the gut microbiome¹. Benzodiazepines, antidepressants and anti-psychotics affect microbiota activity, with potential neural effects. Conversely, antibiotics can reduce adverse events of drugs such as anti-psychotics.

Future therapies

Each individual has a unique microbiota composition, and this may allow personalized therapeutic treatments

Preliminary data from human probiotic studies indicates that microbiota manipulation is a potential treatment, or adjuvant therapy, for a number of psychiatric conditions, but further studies are needed.  Dietary alterations can also be important, as the ‘Mediterranean’ style diet is associated with lower rates of depression, and beneficial effects on gut microbiota¹.

Fecal microbiota transplantation is another therapy for microbiota manipulation, which has been used successfully in recurrent Clostridioides difficle infection. There are potential risks such as infectious disease transfer and development of chronic disease⁷, and it is unclear whether the gut microbiota changes are maintained long-term⁸.

Each individual has a unique microbiota composition, and this may allow personalized therapeutic treatments in the future.