The gut-brain connection: A macro study links digestive disorders with neurodegenerative diseases

Modern medicine has achieved great success in narrowing down problems, attempting to reduce them to make them manageable. There are now specialists who deal with gastric, cardiac, or neurological disorders, but it is well known that the human body is not compartmentalized. The ability to make sense of vast amounts of data provided by new technologies is helping to break down barriers between specialties that have been useful until now.

One of the connections that is generating the most interest is the one between the gut and the brain. It has long been observed, for example, that the insulin resistance that causes type 2 diabetes has also been observed in neuronal areas of people with Alzheimer's, and disruptions in this two-way communication axis, which connects the digestive system, immune system, metabolism, and brain, have broad implications for health. Today, the journal Science Advances publishes a study examining the connection between the gut and the brain and how digestive or metabolic disorders increase the risk of Alzheimer's or Parkinson's .

The work, led by Sara Bandrés, director of the Neurogenetics area at the Center for Alzheimer's and Related Dementias at the NIH (National Institutes of Health of the USA), sought to understand which disorders could increase the risk of suffering from neurodegenerative diseases before neurological symptoms appear, how intestinal problems affect the reliability of blood biomarkers used to detect Alzheimer's or Parkinson's, and to see if combining all this medical, genetic or molecular data improved the ability to predict who will develop these diseases.

To achieve this goal, the researchers applied statistical and artificial intelligence models to millions of health and genetic data points from three large international repositories: the UK Biobank, which holds genetic, medical, and proteomic information on more than 500,000 individuals; the SAIL Databank in Wales, which holds anonymized medical records from hospitals and primary care; and the FinnGen Biobank in Finland, which holds more than half a million biological samples and clinical data.

Researchers identified many digestive and metabolic problems associated with an increased risk of neurodegenerative diseases. Among the most striking findings, they found that diabetes is linked to an increased risk of Alzheimer's and Parkinson's when diagnosed up to 15 years before the neurological disease. For example, a diagnosis of type 2 diabetes more than a decade before the onset of Alzheimer's increases the risk of developing it by up to 70%. Another relevant marker is vitamin D deficiency , but an increased risk was also seen in association with gastritis, esophagitis, intestinal infections, and cholesterol disorders.

The study also observed that people with Alzheimer's and Parkinson's disease and associated intestinal problems had a lower genetic predisposition to these neurodegenerative diseases. "This finding reinforces the idea that not everything is written in the genes: the environment, metabolism, and intestinal health can tip the balance toward disease or protection. Our data suggest that, when gut-brain axis disorders come into play, genetics weigh less and environmental factors may play a more determining role in the risk of developing neurodegeneration," Bandrés points out.

In addition to improving early detection, understanding the connections between the gut and the brain offers the possibility of disease prevention. Controlling diabetes is one way to reduce the likelihood of developing Parkinson's or Alzheimer's, and trials are already testing antidiabetic drugs as treatments for these conditions. Correcting nutritional deficiencies, such as a lack of vitamin D or B vitamins, which are associated with Alzheimer's and Parkinson's respectively, and using appropriate supplements can reduce the impact of neurodegenerative disorders.

“Today, we don't have a single, specific test that tells us 'your gut is predisposed to an increased risk of Alzheimer's or Parkinson's,'” Bandrés acknowledges. However, she states, “there are clinical tools that allow for a more precise assessment of gut health. For example, clinical diagnoses of functional digestive disorders, such as irritable bowel syndrome, chronic constipation, or functional diarrhea, which are already recognized as warning signs in our studies,” she adds. “Furthermore, research into gut microbiota is advancing rapidly: changes in the composition of the bacteria that inhabit our gut could become a promising approach for detecting early imbalances that, over time, impact brain health,” she concludes.

"These data corroborate existing evidence about the so-called gut-brain axis, so it is considered important to pay attention to these intestinal pathologies in order to closely monitor patients and attempt to make an early diagnosis of neurodegenerative brain diseases," says José Luis Lanciego, senior researcher of the Gene Therapy Program in Neurodegenerative Diseases at the Center for Applied Medical Research (CIMA) of the University of Navarra, who did not participate in the study.

“The digestive system is often considered the second brain, as it has numerous neurons in its submucosal layer. It is connected bidirectionally to the brain through the vagus nerve. There is considerable evidence demonstrating a key role of the intestinal microbiota and its alterations, known as intestinal dysbiosis, in triggering neurodegenerative brain diseases,” Lanciego points out. “In fact, a few days ago it was shown that when a certain bacteria present in people with poor oral health is administered to mice, they develop deposits of the protein called beta-amyloid in the form of plaques very similar to those present in the brains of patients with Alzheimer's disease,” he exemplifies.

The recently published study is another step in the effort to understand the complex connections between the body's various systems, begin to interpret their effects on health, and develop more comprehensive medicine using scientific methods.