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.

Breastmilk varies between mothers – affects microbiome of infant

Chemical structure of fucose molecule

We know that breastmilk is crucial to the development of a healthy infant’s microbiome.  It contains many oligosaccharides that cannot be digested by the infant, and whose primary purpose appears to be stimulating the growth of specific microbiome bugs.  There are, however, differences between new mothers’ milk.  For instance, some mothers cannot produce 2′-fucosylated oligosaccharides, which are oligosaccharides that have a fucose sugar on the end.  David Mills and his team at UC Davis recently investigated how the microbiomes of infants differed based on the presence or absence of fucosylated glycans in the milk that they drank.  They published their work in the journal Microbiome last week.

Forty four infants who were fed breast milk had their microbiomes measured throughout the first 120 days of their lives.  Thirty two of these infants were fed milk from woman with fucosylation ability (secretors), and twelve were from women without the fucosylation ability (non-secretors).  When the researchers investigated the contents of the milk they found that it varied in many ways, besides fucosylation.  For example, those women that did not fucosylate appeared instead to increase their monosaccharide sialylation, a sugar that has been linked to C. difficile infection.  When the scientists compared the infants’ microbiomes in the two groups they discovered that secretor-fed infants achieved higher levels of Bifidobacteria and Bacteroides, and achieved these levels more quickly than non-secretor-fed infants.  Instead, the non-secretor-fed infants had relatively higher levels of Enterobacteria, Clostridia, and Streptococci.

These differences may be important to the infants’ developments.  For example, Bifidobacteria in the gut is associated with lower gut permeability and less inflammation.  Also, Bifidobacteria and Bacteroides are large contributors to the production of short chain fatty acids and lactate, which have each been associated with gut health time and time again.  A full 20% of the U.S. population is non-secretors, and it would be interesting to see if any epidemiologically significant differences exist between the two groups into adulthood.  In either case, in the future it may be worth considering supplementing infant milk with fucosylated oligosaccharides if the lack of fucosylation does turn out to be detrimental to the baby.

Changes in the microbiome may affect how we age

Betty White has aged so well because of her microbiome.  Photo by David Shankbone, 2010

Many people have researched the microbiome shift between infancy and adolescence, but very few have researched the changes in the microbiome that occur in the elderly.  A new study out of Canada, published in the Journal Microbiome, did just that.  Their results show that the frailty associated with old-age may be related to the bacteria in our guts.

The study used groups of mice that were either young, middle aged, or old.  They then measured the frailty of these mice which, as one would expect, was tied closely with age.  The researchers then studied the microbiome of these mice, as well as the genes expressed by the bacteria, so as to gain an understanding of what the bacteria are actually doing.

The scientists discovered that, when compared to young and middle aged mice, the old mice were abundant in bacteria that could break down simple sugars, but were underrepresented in bacteria that could break down more complex sugars, as well as lactate.  This is important because increased lactate in the stool has been associated with ulcerative colitis and other inflammatory bowel diseases in older humans.  The old age mice also consisted of less bacteria that could produce vitamins B12 and B7.  Both are important vitamins and the lack of B7 has been linked to colon cancer.  Finally, the old-age mice had bacteria that would rapidly degade creatine.  Creatine is known to build muscle, so constantly breaking it down may cause the decrease in muscle mass observed in the elderly.

Clearly there are changes in the microbiome as we age, and these changes must come with some consequences.  As the authors of this paper suggest, perhaps the microbiome holds to key to the difference between aging like a fine wine and aging like moldy cheese.