Two new studies are offering yet more evidence the gut microbiome is deeply intertwined with our metabolic and brain health. One study offers some of the first experimental evidence to show a direct relationship between gut bacteria and cognitive changes in a mouse model of Alzheimer’s, while a second suggests microbial biomarkers in the gut could be used to predict the progression of prediabetes to type 2 diabetes years ahead of time.
There are trillions of microbes living inside of us, and perhaps one of the more exciting research areas in the 21st century is our growing understanding of the influence these microbes have on our overall health. It is becoming increasingly clear we have a deeply symbiotic relationship with these microbes, and when their populations are out of balance we can suffer deleterious health effects.
The big challenge researchers are facing is understanding how to transform this growing knowledge of the gut microbiome into treatments for disease. The sheer scale and specificity of each person’s individual microbiome indicates it may be unlikely we find a “one size fits all” therapeutic approach.
Science is often a piecemeal process and microbiome science is no exception. Right now we are very much still in the preliminary stages of understanding exactly how interconnected our gut microbiome is with our general health. A pair of new studies offer two more pieces in this massively complicated puzzle.
The gut, the brain, and Alzheimer’s disease
We know our gut and our brain are intimately connected in a number of unique ways. And, we also know those connections are bi-directional. Traumatic brain injury, for example, has been found to lead to subsequent changes in a person’s gut microbiome, while on the other hand, certain gut bacteria is thought to directly reduce neuroinflammation.
A number of studies have detected connections between microbiome alterations and neurodegenerative diseases including Alzheimer’s and Parkinson’s. A new study, led by scientists at Oregon Health & Science University and published in the journal Scientific Reports, is offering the first experimental demonstration in animal models of a direct connection between gut microbiome alterations and cognitive changes.
The study looked at two groups of mice: one group engineered to carry genes known to be associated with Alzheimer’s disease, and the other was a healthy wild-type group. Both groups were raised for six months under exactly the same conditions, and fed the same diet.
After six months the researchers discovered notable behavioral and cognitive differences between the two groups. Differences were also detected in microbiome composition between the two groups.
"You know the expression, 'You are what you eat?'" says Jacob Raber, senior author on the new study. "This may be part of that. While all mice were fed the same diet, the gut microbiome is affected in a genotype-dependent fashion and this in turn might affect your brain."
Further homing in on the mechanisms at play the researchers discovered a relationship between the gut bacteria differences in the Alzheimer’s group and epigenetic changes in hippocampal brain tissue. Raber suggests the causal direction of this relationship is unclear, but it is clear there is connection between epigenetic changes in the brain and specific microbes in the gut.
"Microbes may elicit an impact on behavioral and cognitive measures relevant to Alzheimer's disease via epigenetic changes in the hippocampus," says Raber. "Or, alternatively, it might be that the epigenetic changes in the hippocampus affect changes in the gut microbiome."
Can diabetes disease progression be foreshadowed by microbiome changes?
Our gut bacteria can have a pretty marked and immediate influence on our metabolism. As bacteria in our gut feast on the food we consume they then poop out metabolites that can directly affect everything from blood sugar levels to the synthesis of neurotransmitters such as serotonin.
Type 2 diabetes is not a condition that appears overnight. Preceding a clear diagnosis one’s blood sugar levels can slowly rise over months, or even years, before noticeable symptoms lead to a clinical diagnosis. This early stage of the disease is referred to as prediabetes.
A compelling study last year found subjects in a prediabetic stage demonstrate clear microbiome differences compared to healthy subjects. Certain gut bacteria imbalances were found to correlate with the earliest stages of the disease. Of course, as with the Alzheimer’s research, the causal direction of the relationship is still very much unclear.
A new study set out to look at microbiome changes over time and how they correlate with subjects progressing from prediabetes to type 2 diabetes. Longitudinal data from more than 600 subjects allowed the researchers to investigate whether a specific microbiome signature can predict the onset of type 2 diabetes.
A machine learning model was constructed to find microbiome patterns that could predict metabolic changes at two time points: 18 months and four years into the future.
"This is one of the first studies that assess the role of the gut microbiome in type 2 diabetes over time," says first author on the study, Oliver Aasmets. "Our study design allowed us to compare predictions made a year and a half and four years ahead, which showed significant differences, giving input for further studies.”
The new research suggests the gut microbiome may be a useful predictive tool to evaluate a person’s risk of developing type 2 diabetes. But, as the study makes quite clear, the “high variability and personalization of the human gut microbiome leads to large variations in the performance estimates”.
Plus, the causal direction of the relationship is again not clear. It is unlikely gut bacteria is solely driving the progression of the disease. Realistically it's more likely an incredibly complex bi-directional relationship is at play.
Translating these piecemeal findings into clinical therapies is no small task. We certainly are not on the precipice of finding a magical probiotic that will be a cure-all for diabetics or Alzheimer’s sufferers. But in the short-term these findings could offer doctors new ways to catch those patients most at risk of developing certain diseases. This knowledge would help target treatments at earlier stages and hopefully stave off the worst of these metabolic and neurodegenerative diseases.
"Using gut microbiome as a risk factor for predicting various diseases is a promising research area, but further studies in different populations and with larger sample sets are needed in order to validate the results and to further develop the prediction models," says Elin Org, lead author on the new diabetes/microbiome study.
The Alzheimer’s/microbiome study was published in the journal Scientific Reports.
The diabetes/microbiome study was published in the journal mSystems.
Source: OHSU, Estonian Research Council