The oral microbiome of schizophrenics differs from controls

Self-portrait of Vincent van Gogh, who likely had schizophrenia

The gut-brain axis is a very intriguing field that offers a lot of promise in making progress in neurological diseases.  The science is still very new, though, so much work needs to be done in establishing any connections between the microbiome and these diseases.  The reason the gut is normally explored is because of the strong connection between the gut and the brain via the vagus nerve, which in initial studies has been shown to be an important pathway for afferent and efferent connections.  Other body microbiomes’ connections to the brain have not yet been studied.  A new study that came out last week makes a connection between the oral microbiome and schizophrenia, a disease which had previously been linked to the gut microbiome.  The results were published in the journal PeerJ.

The scientists performed whole genome sequencing on the oropharyngeal microbiomes of 16 people with schizophrenia and 16 healthy people.  Importantly, the scientists note that the people with schizophrenia were more likely to be smokers and to be overweight, two qualities that are already associated with alterations of the oral microbiome.  The results showed that the schizophrenics had lower overall diversity of their oral microbiomes compared to controls.  Specifically, lactic acid bacteria, and especially Lactobacillus gasseri, were more abundant in the mouths of those with schizophrenia, even after controlling for other variables such as age and smoking status.

While this paper does not attempt to explain why these differences occur, they are quite interesting nonetheless.  If somehow the disease state can be characterized by the oral microbiome this could be important for diagnostics.  The next step is to actually establish if any of the connections between the bacteria in the body (including the mouth) and the brain are partly responsible causing the disease.  If this is the case then not only would it help explain the environmental causes of schizophrenia, but it would also lend itself to possible microbiome treatments for the disease, such as pro- or pre-biotics.

Identifying probiotics using healthy individuals for preventing oral disease

The oral microbiome consists of many hundreds of species of bacteria, some harmful and some beneficial. The importance of a healthy microbiome should be stressed not only because having clean, white teeth looks good but because diseases like periodontitis increase risk of other issues such as respiratory infections and inflammatory diseases. Having unhealthy teeth can cause more systematic problems than you would think. Probiotics, different from antibiotics, are one way that microbiome science is combating the colonization of harmful bacteria in the body. Many researchers have investigated using probiotics to maintain a normal healthy oral microbiome, and in a new study published last week, scientists researched probiotics that may reduce the smell of “bad breath” that is caused by volatile sulfur compounds, and prevent cavities and periodontitis.

The study, performed by researchers at the Yakult Central Institute for Microbiological Research in Tokyo, Japan (a division of Yakult, the makers of yogurts and probiotics),  was aimed toward finding new potential probiotic candidates. Thirty-two volunteers were recruited and selected based on factors such as non-smoking habits, no large cavities or bleeding on probing, and no bad breath. Oral bacteria samples were taken from multiple specific locations in the mouth of the volunteers. The bacteria were cultured in a lab and tested for the characteristics that follow: lack of production of volatile sulfur compounds (causes bad breath) and water insoluble glucan (causes cavities), antibacterial activity against bacteria that cause periodontitis, ability to healthily adhere to teeth and cells in the mouth, and caused no infections in an artificial mouth system or in a rat model.

After culturing in a lab and testing the criteria on 896 oral samples from the 32 participants, the study found that Lactobacillus crispatus YIT 12319, L. fermentum  YIT 12320, L. gasseri YIT 12321, and Streptococcus mitis YIT 12322 are good candidates for probiotics.  The next step is to now test for these probiotics’ effects in the mouths of many people, and likely develop a product.  Interestingly, L. crispatus and L. gasseri are two of the major bacterial strains found in a healthy vaginal microbiome, and perhaps this suggests a route of access for these bacteria to access the vagina. In any case, the promise of new ways to help maintain a healthy oral microbiome is exciting, and it is encouraging to read papers from major companies that have the ability to actually manufacture products in this space.

Schizophrenia and the virome

Schizophrenia PET scan

Schizophrenia is a mental health disorder in which people cannot recognize reality, suffer from hallucinations, and experience social withdrawal.  The causes of schizophrenia are unknown, but it is thought to include genetic, environmental, psychological, and social risk factors.  As we have written about extensively in this blog, the bacteria and viruses in our body have an important connection to our brain and behavior, in what has been termed the ‘gut-brain axis’.  Considering the gut-brain axis, a team of scientists from Johns Hopkins University wondered if the microbiome, and specifically the virome, was somehow related schizophrenia.  They recently published their findings in Schizophrenia Bulletin.

The scientists sampled the throat microbiome from 74 people in the Baltimore, MD area, 41 of whom suffered from schizophrenia and 33 of whom did not.  They discovered that a specific bacteriophage (virus that infects bacteria), Lactobacillus phage phaidh, was linked to schizophrenia, which was found in 17 of the 41 schizophrenia patients, but only 1 of the 33 control individuals.  In addition, 9 of those 17 schizophrenics had a comorbid immune disorder, such as diabetes or Crohn’s disease, whereas only 2 of the remaining schizophrenics without the phage had these diseases.  The scientists also found a loose link between taking the drug valproate and occurrence of the phage.  Interestingly, this drug has been previously shown to affect the microbiome.  Finally, the existence of the phage coincided with higher levels of the bacteria that the phage attacks, Lactobacillus gasseri.  This is an unsurprising result because a phage and its target are usually found together.

The scientists acknowledge that the results of this study do not prove any real association between the microbiome and schizophrenia, but based on the results, they suggest that further research is warranted.  Notably, Lactobacillus gasseri is sometimes included in probiotics to supposedly relieve gastrointestinal issues.  However, if gasseri’s phaidh phage goes along with it, then according to this study, it may cause more harm than good.