The microbiome is gaining a great deal more attention of late as research shows that not only does this bacterial community play a significant role in basic health and immune functioning, it could also impact patient response to treatment and even certain disease states.
One such condition is about as far from the gut—distance-wise, at least—as it's possible to get: schizophrenia.
In a five-year exploration of how the microbiome could affect the brain, researchers collaborated from several universities—including SUNY Upstate Medical University, as well as Chongqing Medical University and Sun Yat-sen University in China, among others—and shared their work in Science Advances in a paper titled “The gut microbiome from patients with schizophrenia modulates the glutamate-glutamine-GABA cycle and schizophrenia-relevant behaviors in mice.”
A significant factor impacting the health of the microbiome is the diversity of bacteria types found in the gut. The researchers sequenced the gut microbiomes of healthy individuals and those with schizophrenia, and found that in the latter, there were noticeably fewer different gut microbiomes.
“Here, we found that unmedicated and medicated patients with SCZ had a decreased microbiome α-diversity index and marked disturbances of gut microbial composition versus healthy controls (Hcs),” the authors noted. “Several unique bacterial taxa (e.g., Veillonellaceae and Lachnospiraceae) were associated with SCZ severity. A specific microbial panel (Aerococcaceae, Bifidobacteriaceae, Brucellaceae, Pasteurellaceae, and Rikenellaceae) enabled discriminating patients with SCZ from HCs with 0.769 area under the curve.”
Team members had previously explored the impact of the gut microbiome on depression, and used that data to compare the OTUs highlighted for schizophrenia with those pinpointed in major depressive disorder. As explained in the paper, “Previously, we identified 54 OTUs able to discriminate between depressed and HC subjects (12). Compared to the HC group, only 15.3% OTUs (8 of 52) belonging to Ruminococcaceae were up-regulated, and 30.3% OTUs (24 of 79) belonging to Acidaminococcaceae, Bacteroidaceae, Ruminococcaceae, and Veillonellaceae were synchronously down-regulated, in both SCZ and depression groups (fig. S3). These findings indicate that the altered gut microbial composition observed in SCZ is specific relative to the gut microbiome changes we observed in depression.”
The researchers were also able to relate specific strains to schizophrenia symptoms. They found that “Veillonellaceae OTU191 was negatively correlated with PANSS, whereas Bacteroidaceae OTU172, Streptococcaceae OTU834, and two Lachnospiraceae OTUs (477 and 629) were positively correlated with PANSS. Ruminococcaceae also had two OTUs correlated with PANSS, one negatively correlated (OTU725) and the other positively correlated (OTU181).”
PANSS is the Positive and Negative Syndrome Scale, which is used to measure the severity of schizophrenia symptoms. “Positive” symptoms include symptoms such as hallucinations, while “negative” symptoms include movement disorders or memory issues.
In addition to this analysis, the team also transplanted the microbiomes from individuals with schizophrenia into germ-free mice. As the authors reported in their results, these mice “displayed locomotor hyperactivity, decreased anxiety- and depressive-like behaviors, and increased startle responses.”
Dr. Julio Licinio, a professor of psychiatry, medicine and pharmacology, who serves as dean of the College of Medicine at Upstate and co-led the study, noted in a SUNY Upstate press release that “The mice behaved in a way that is reminiscent of the behavior of people with schizophrenia. The brains of the animals given microbes from patients with schizophrenia also showed changes in glutamate, a neurotransmitter that is thought to be dysregulated in schizophrenia.”
By comparison, germ-free mice that received transplants of microbiomes from healthy individuals displayed no unusual behavior.
“We understand schizophrenia as a brain disease,” said Dr. Ma-Li Wong, Upstate professor of psychiatry and behavioral science and neuroscience and physiology, who also co-led this research. “But maybe we need to re-examine this line of thinking and consider that maybe the gut has an important role.”
The authors pointed out that the impact of medication is not likely to have skewed their results. Though most of the patients who were sampled for this work were taking antipsychotic medication, it was noted in the paper that "the distributions of global microbial phenotypes did not vary between medicated and unmedicated patients with SCZ (fig. S2, B and C), or with respect to medication type."
“Our findings support the possibility that alterations of gut microbiota may potentially participate in the onset and/or pathology of [schizophrenia] through modulating MGB [microbiota-gut-brain] metabolic pathways … Together, our findings have potential clinical diagnostic value, with treatment implications, and lay the groundwork for further identification of “signature patterns” of defined gut microbes in [schizophrenia],” the authors concluded.