Sometimes, the link between microbes and disease is obvious. The presence of a certain bacteria in the gut, for instance, is thought to protect against an inflammatory gastrointestinal disease. But researchers studying the microbiome – the system of microbes living in and on the human body -- are finding that bacteria residing in one place in the body can also affect organs in another location. Studies in recent years that have linked heart attack risk to certain oral microbes are a good example.

Now, researchers are exploring a connection between the oral microbiome and dementia. Christopher Cuff, a professor of microbiology and immunology at West Virginia University School of Medicine, says his investigation started when colleagues at the WVU School of Dentistry wanted to know how oral health affects quality of life in older West Virginians who live in nursing homes and similar communities. After doing some background reading and collaborating with the dental researchers, Cuff saw "tantalizing hints that oral health was related to cognitive function."

In a pilot study published in Investigative Genetics in September, Cuff and his team described taking oral swabs from 10 patients, 70 years or older. Five had been diagnosed with dementia. The rest had either normal cognitive function or some cognitive impairment unrelated to dementia. Using high-throughput sequencing methods, the researchers were able to obtain more than 2 million high-quality DNA sequences per sample.

Cuff says analysis of the data showed fairly obvious differences between patients with dementia and all others. "There were two potential outcomes that we thought we could find if there was a difference," Cuff says. "We thought we would find phylotypes or species that were unique to dementia versus not dementia, or that the composition [of bacterial populations] would be different."

The researchers' genomic sequencing didn't go deep enough to count specific species of bacteria, but they did find a difference in the bacterial composition at the family level. In particular, Cuff says, there was a higher level of fusobacteria—strains of which are known to contribute to several diseases, including periodontal disease—in normal and impaired-but-not-demented patients than in the patients with dementia. "It may not be the presence of certain bacteria that promote dementia, but the absence of some potentially neuro-protective bacteria," he says.

Even more surprising to Cuff was a marked difference in the samples. Working with such a small number of patients, he didn't expect a visible difference in the numbers or types of bacteria between patients with and without dementia. But, he says, "If you look at the figures in the data, you can see it."

Cuff is cautious about drawing conclusions. As he and his colleagues point out in their paper, the results — though consistent — don't rise to the level of statistical significance under robust analysis. But the study did provide enough evidence to suggest a link between the oral microbiome and dementia, so the team plans to pursue the hypothesis by conducting a larger study with a greater number of patients.

Cuff says they'll investigate the mechanisms that might explain their results and will test whether certain bacterial populations are protective or harmful. The team is also planning to see if some bacteria contribute to inflammation in the body, which might precede diseases like dementia.

Eventually, Cuff would like to study the metagenome — all of the bacterial genes present at once in a given sample—as opposed to separate bacterial species. "This era of making lists of microbes at various anatomic sites is just phase one of microbiome analysis," Cuff says. "We have to move on to metagenomics to really understand how the microbiota are affecting human health."

Source: New York Genome Center