In recent years, researchers have uncovered various ways the microbiota interacts with the brain through the so-called gut-brain axis and there’s now a large body of literature that demonstrate the gut microbiota of patients with various psychiatric disorders is different from that of people without such disorders.
"Differences in the levels of a wide range of specific bacteria have been proposed as potential biomarkers for individual disorders like depression, anxiety, psychosis and so on. However for these to be truly considered a biomarker, the specificity of the microbial alterations needs to be demonstrated," Allan Young, one of the research paper's authors, explains in an interview for the publishing journal 'JAMA Psychiatry'.
"Therefore we did a trans-diagnostic comparison in order to assess whether these alterations are truly disorder specific and thus can be biomarkers.”
The review and meta-analysis included 59 studies which provided 64 case-control comparisons capturing 2643 patients and 2336 controls from across the world.
The team performed a ‘cleaning of the data’ to reduce the possibility of false positives – a common concern in this field – by removing all the results that were reported just once. A second cleaning was done to group findings according to the research group. If a finding was only reported by one research group, this was also removed.
After data cleaning, they summarised results for each disorder and looked at whether there was a consensus on which taxon were significantly decreased or increased. They then compared findings trans-diagnostically.
The report concludes that differences in beta diversity were consistently observed only for major depressive disorder, psychosis and schizophrenia. Regarding relative abundance, little evidence of disorder specificity was found. Instead, a transdiagnostic pattern of microbiota signatures was found.
Depleted levels of Faecalibacterium and Coprococcus and enriched levels of Eggerthella were consistently shared between major depressive disorder, bipolar disorder, psychosis and schizophrenia, and anxiety, suggesting these disorders are characterized by a reduction of anti-inflammatory butyrate-producing bacteria, while pro-inflammatory genera are enriched.
Young explains: "We found that there were very few distinct condition specific alterations. Instead, what we saw was conditions such as depression, bipolar disorder, psychosis/schizophrenia and anxiety had a similar pattern in changes of microbial abundance.
"For example, the most notable and consistent changes were the depletion of the genus Faecalibacterium and Coprococcus and the enrichment of Eggerthella in patients versus controls."
He explains Faecalibacterium and Coprococcus are connected with SCFA production and have anti-inflammatory properties whereas Eggerthella is involved in butyrate depletion and has been linked to inflammation.
"These are early indications of overlapping pathophysiologies that these changes are associated with in patients with depression, psychosis, anxiety, bi-polar disorder.
"We've argued that the alterations we see in the microbiota are better explained by overlapping pathophysiology rather than distinct clinical diagnoses...
"We are suggesting we can lump some of these disorders together in terms of the alteration in the microbiome but that may allow further stratification and personalisation in the future."
A significant step for product development
Miguel Toribio-Mateas, lecturer in nutrition, microbiome and gut-brain axis, and visiting research scholar at London South Bank University, says this is particularly noteworthy for R&D professionals in the microbiome space as it provides solid insights for future product developments.
“Conditions included in this meta-analysis included anxiety, depression, which have had a huge impact on the general population as a result of the pandemic. The study also identified the similar patterns in bipolar, schizophrenia, anorexia nervosa, attention deficit and hyperactivity disorder (ADHD), obsessive compulsive disorder (OCD), and post-traumatic stress disorder (PTSD).
"For R&D professionals in the gut microbiome and mental wellbeing space, this study is really significant because it provides us with clear insights to guide our product development. We should be striving to develop products containing ingredients that help with the growth of well-known butyrate producers such as Faecalibacterium, Roseburia or Coprococcus, whilst helping keep potentially pathogenic microbes such has Eggerthella, Klebsiella and Streptococcus at bay.”