Biological overlap?
The alpha-diversity meta-analysis encompassed 34 studies (n = 1,519 patients, 1,429 controls). The researchers found significant decreases in microbial richness in patients, compared with controls (observed species standardized mean difference, −0.26; 95% CI, −0.47 to −0.06; Chao1 SMD, −0.5; 95% CI, −0.79 to −0.21). On the other hand, when they examined each diagnosis separately, they found consistent decreases only in bipolar disorder. There was a small, nonsignificant decrease in phylogenetic diversity between groups.
MDD, psychosis, and schizophrenia were the only conditions in which differences in beta diversity were consistently observed.
“These findings suggest there is reliable evidence for differences in the shared phylogenetic structure in MDD and psychosis and schizophrenia compared with controls,” the authors write.
However, “method of measurement and method of patient classification (symptom vs. diagnosis based) may affect findings,” they added.
When they focused on relative abundance, they found “little evidence” of disorder specificity, but rather a “transdiagnostic pattern of microbiota signatures.”
In particular, depleted levels of Faecalibacterium and Coprococcus and enriched levels of Eggerthella were “consistently shared” between MDD, BD, psychosis and schizophrenia, and anxiety, “suggesting these disorders are characterized by a reduction of anti-inflammatory butyrate-producing bacteria, while proinflammatory genera are enriched.”
“The finding that these perturbations do not appear to be disorder-specific suggests that the microbiota is affected in a similar manner by conditions such as depression, anxiety, bipolar disorder, and psychosis,” said Ms. Nikolova.
“We have seen similar findings from previous meta-analyses of inflammatory marker studies and genetic studies, for example, suggesting that there is a biological overlap between these conditions, which we have now also seen in the microbiota.”
The authors highlighted potential confounders, including study region and medication use.
Conditions such as MDD, psychosis, and schizophrenia were “largely investigated in the East,” while anorexia nervosa and OCD were primarily investigated in the West.
Moreover, comparing results from medication-free studies with those in which 80% or more of patients were taking psychiatric medication showed increases in bacterial families Lactobacillaceae, Klebsiella, Streptococcus, and Megasphaera only in medicated groups, and decreases in Dialister.
In light of these confounders, the findings should be considered “preliminary,” the investigators noted.
Greater standardization needed
Commenting on the study, Emeran Mayer, MD, director of the Oppenheimer Center for Neurobiology of Stress and Resilience at the University of California, Los Angeles, said it is “intriguing to speculate that low-grade immune activation due to reduced production of butyrate may be such a generalized factor affecting microbial composition shared similarly in several brain disorders. However, such a mechanism has not been confirmed in mechanistic studies to date.”
In addition, the study “lumps together a large number of studies and heterogeneous patient populations, with and without centrally acting medication, without adequate dietary history, studied in different ethnic populations, studied with highly variable collection and analysis methods, including highly variable sample and study sizes for different diseases, and using only measures of microbial composition but not function,” cautioned Dr. Mayer, who was not involved in the research.
Future studies “with much greater standardization of subject populations and clinical and biological analyses techniques should be performed to reevaluate the results of the current study and confirm or reject the main hypotheses,” asserted Dr. Mayer, who is also the founding director of the UCLA Brain Gut Microbiome Center.
Ms. Nikolova is funded by a Medical Research Council PhD Studentship. Other sources of funding include the National Institute for Health Research Biomedical Research Centre at South London and Maudsley National Health Service Foundation Trust and King’s College London. Ms. Nikolova has disclosed no relevant financial relationships. Dr. Mayer is a scientific advisory board member of Danone, Axial Therapeutics, Viome, Amare, Mahana Therapeutics, Pendulum, Bloom Biosciences, and APC Microbiome Ireland.
A version of this article first appeared on Medscape.com .