Lindsay Hall from the Quadram Institute has contributed to a comprehensive review to answer a question of how psychiatric disorders are linked to changes in the gut microbiome.

The review was led by Viktoriya Nokolova and colleagues from the Institute of Psychiatry, Psychology & Neuroscience at King’s College London and has been published in the leading journal JAMA Psychiatry.

Over the last century, scientists and clinicians have explored links between gut health and mental health. As our understanding has increased, more and more evidence has pointed to a role for the gut microbiome, the population of trillions of different bacteria and microbes that colonise the gut.

With advances in genetic sequencing technology, labs across the world now have the ability to not only identify which species of microbe are present in the microbiome but understand from reading the sequence of individual genes what functions those microbes might have.

This has led to many attempts to identify characteristic changes in the profile of microbes in the microbiome associated with different psychiatric conditions, compared to people without the condition. These don’t tell you whether the microbiome changes cause a condition to develop or are an effect of that condition. But a characteristic pattern of changes in the microbes could be used to aid diagnosis, or to monitor whether treatments are effective.

To act as a reliable biomarker in this way, gut microbiome changes need to be specific to a condition and reproducible. A single study may not be enough to establish this, but combining the results of numerous studies, through a systematic review of published results, can overcome problems of reproducibility or even contradictory results. This has identified microbiome patterns that show good promise for adoption as biomarkers for a number of mental health conditions.

But is there an overall pattern of microbiome disturbance underlying all psychiatric disorders? Or are there distinct changes associated with the diagnosis of different conditions?

These are the questions that the researchers set out to answer in this new meta-analysis. They searched for published results of previous analyses on the changes in the gut microbiome of adults with bipolar disorder, psychosis and schizophrenia, major depressive disorder, anorexia nervosa, anxiety, obsessive compulsive disorder, posttraumatic stress disorder or attention-deficit/hyperactivity disorder.

After excluding some studies based on pre-determined markers for quality, the researchers reviewed 34 different studies that compared over 1500 people with those conditions with control groups of people.

Their findings indicated that across certain disorders there is a shared pattern of microbial change, specifically across psychosis and schizophrenia, bipolar disorder, anxiety and major depressive disorder (MDD).

Eggerthella bacteria were particularly enriched in samples taken from people with these conditions. These bacteria have previously been associated with gastrointestinal inflammation. Other types of bacteria that are thought to have anti-inflammatory properties were conversely depleted – in particular Faecalibacterium and Coprococcus. In a healthy microbiome, these bacteria produce a molecule called butyrate, one of a number of short chain fatty acids that maintain the lining of the gut and reduce inflammation. In context of this transdiagnosis pattern, there was little, or very weak, evidence for microbiome changes associated with each specific condition.

However, it’s important to note that this review provides no evidence of how the functions of the microbiome relate to psychiatric disorders, only the composition of different species. But some studies have linked short-chain fatty acid synthesis with psychiatric illness. Functional studies of the gut microbiome and brain are an exciting emerging area for research.

This first ever meta-analysis provides some preliminary indications of an underlying pattern of changes in the gut microbiome linked to mental health. It aligns with other genetic and inflammatory marker studies that support a transdiagnostic dimensional model of psychiatric disorders, that cuts across the current range of disorder categories.

However, it is limited by the range of studies that have so far reported, and any inherent weaknesses of these. For example, most studies had quite small numbers of participants, and for some conditions there were very few studies at all. Studies also underrepresent people in low- to middle income countries. Other factors that affect the microbiome composition, such as diet and geographic location, or medication, need to be taken into account. As more and more microbiome studies are undertaken and report, these gaps may be filled and the strength of similar meta-analyses will improve, but this relies on better harmonisation of methods and data sharing.

‘There is a growing body of evidence that the gut microbiota may play an important role in brain function, and that disturbances in these microbial communities may contribute to development of certain neurological conditions’ said Professor Lindsay Hall.

‘This umbrella review adds to this evidence base, by identifying certain microbes that may be linked with specific psychiatric disorders, rather than a microbiota signature that is apparent across multiple conditions. However, it is evident from this review that there is a pressing need for larger scale and well controlled studies in this area so that clearer profiles can be defined, which may identify new biomarkers and allow development of therapies for different psychiatric disorders.’

The researchers hope that this review will provide a vital resource for these future studies, providing a wider background of the changes in the gut microbiome associated with mental health against which individual studies into specific disorders can be compared.

Reference:

Perturbations in Gut Microbiota Composition in Psychiatric Disorders, Viktoriya Nikolova, Megan Smith, Lindsay Hall, Anthony Cleare, James Stone and Allan Young, JAMA Psychiatry DOI: 10.1001/jamapsychiatry.2021.2573