Dementia: Do gut bacteria play a role?
Dementia is a widespread neurocognitive condition, but scientists are still learning what factors may predispose to — or protect from — its development. Recent research indicates that the gut microbiota may play a complex role. We spoke to two experts on neurocognitive and neurological conditions to find out more.
Dementia is a general term for a range of progressive diseases that affect the brain. The most common types of dementia include Alzheimer’s disease, vascular dementia, mixed dementia, and Lewy body dementia.
These conditions have similar characteristics, including a reduced ability to think, remember and make decisions and potential problems with communication and visual perception.
Biologically, dementia results from the damage or loss of nerve cells called neurons in the brain and their connections. When the damage stops the neurons from sending and receiving messages effectively, it affects how the body functions. The symptoms that each person experiences will vary depending on the type of dementia and which neurons are damaged.
Infectious bacteria, viruses, or fungi can cause neuron damage by activating the brain’s inflammatory cells, known as the microglia.
Microorganisms and the gut-brain axis
The gut is home to a wide number of microorganisms, including bacteria and archaea, which are collectively called the gut microbiota or microbiome.
The four main groups of bacteria in the human gut are Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria.
However, the types and numbers of each group are not constant; instead the microbiota is constantly changing. Different factors, such as diet, medication, and disease, can affect its composition.
The human microbiota plays an important role in controlling the body’s normal functions, including infection resistance, enhanced metabolism, inflammation, and prevention against autoimmune conditions. Indeed, it has become apparent that the microbiota affects gut and central nervous system (CNS) processes.
The communication network between the gut and brain is known as the “gut-brain axis” (GBA). The GBA is responsible for linking the emotional and cognitive centers of the brain with digestive functions. Recent studies have shown that these interactions can change depending on the gut microbiota composition.
Medical News Today spoke to Dr. Verna R. Porter, neurologist and director of the Dementia programs at Providence Saint John’s Health Center in Santa Monica, CA, about the impact of the gut-brian axis on dementia.
Dr. Porter said that gut microbes help break down nutrients from our food, explaining that “the digestive process of these microbes results in many different byproducts, some of which eventually enter the brain.”
Specifically, she highlighted the neurotransmitter serotonin, which affects mood, cognition, learning, and memory, noting that “90% of serotonin [..] is a byproduct of gut microbiome metabolism. [A]ppropriate serotonin levels in the brain influence brain health attributes, such as happiness, mood regulations (e.g., anxiety levels), and even sleep. [A] healthy gut microbiome can have important implications for optimal brain health and well-being.”
Microbiota, neuroprotection, and dysbiosis
The interaction of gut microorganisms with the body’s processes can be mutually beneficial. The immune system has evolved to protect the body from the resident microorganisms, and in turn, they take part in processing the food we eat.
Gut bacteria produce short-chain fatty acids, which break down indigestible fibers from food. The compounds or metabolites produced by the process can reduce inflammation, strengthening the gut barrier. In particular, butyrate molecules can reinforce the blood-brain barrier, which neurodegeneration can disrupt.
If the microbiota loses its balance — a state called dysbiosis — it can promote systemic inflammation. Dysbiosis has links to cardiovascular diseases, autism, anxiety and depression, dementia, and gastrointestinal disorders, such as irritable bowel syndrome.
In addition to dysbiosis, the metabolites generated by the microbiome can interact with the body’s normal processes. Scientists have also identified these “bioactive” molecules as risk factors for disease.
Indeed, certain types of heart failure have links to swelling of the bowel wall and movement of bacteria into the systemic circulation, which, in turn, increases inflammation, contributing to worsening heart failure and atherosclerosis.
Microbiota, nutrition, and dementia
Obesity and poor nutrition also have links to cognitive decline and dementia. The mechanisms responsible remain largely undiscovered, but research has targeted changes in the GBA and inflammation.
There are links between high fat and sugar-rich diets and changes in the gut microbiota composition, which may trigger inflammation.
Experiments in mice have shown that increased Bilophila wadsworthia bacteria in the gut worsens cognitive impairment by directly affecting the hippocampus, the brain region responsible for critical thinking and learning.
Scientists showed that mice on a high fat, low carbohydrate diet made 30% more errors navigating a maze than mice fed on a standard diet.
High sugar, high fat, low fiber diets reduce the number of fiber-digesting bacteria in favor of less-beneficial bacteria. The production of essential metabolites, such as butyrate, also drops.
A recent study by Dr. Naoki Saji, published in Scientific Reports, supports the concept that changes in the microbiota affect dementia risk. The study of microbiome metabolites highlighted different gut microbiota in those with dementia than those without, specifically linking higher fecal lactic acid concentration to a 60% lower risk of dementia.
Speaking to MNT, Dr. Saji explained:
“In the past, we never [thought] of the association between gut and dementia. However, new technology regarding microbiome analysis has revealed it. This new risk factor other than amyloid-beta, a famous factor, may play an important role in the next decade.”
He went on to note that the current study “shows [..] data” to support the notion that people with dementia have a different gut microbiota than those without it.
According to Dr. Porter: “[T]he gut microbiomes of dementia patients have an over-representation of pro-inflammatory bacterial strains that may work to increase inflammation in the brain. It is believed that this pro-inflammatory milieu can, in turn, promote the development of amyloid plaques in the brain — a pathophysiological ‘signature’ associated with Alzheimer’s disease.”
Alzheimer’s disease and microbiota
Alzheimer’s disease is the most common form of dementia, biologically characterized by bundles of amyloid and TAU proteins preventing the transmission of messages from the brain.
Studies in rodents have shown how changes in the animal’s gut microbiome promote the formation of the amyloid bundles, a risk factor for Alzheimer’s.
Analysis of the gut microbiome of people with Alzheimer’s disease has revealed a reduced diversity of microbes. Specifically, researchers have shown lower levels of Firmicutes and Bifidobacterium and a higher level of Bacteroidetes.
Research has also shown that the gut microbiomes of people with dementia have more pro-inflammatory bacteria and fewer anti-inflammatory bacteria.
In her interview with MNT, Dr. Porter discussed a “recent pivotal study” where scientists compared the data of people with Alzheimer’s disease — with and without amyloid — to a control group without Alzheimer’s.
The researchers found that the “elevated presence of pro-inflammatory bacterial strains [and] the decreased presence of anti-inflammatory strains in the microbiomes of the gut had a positive correlation with a heightened inflammatory state. [They also found] higher levels of cognitive impairment and a greater concentration of amyloid deposition in the brain”.
Inflammation also has associations with microbiome metabolites in the circulation system. Research suggests that increased fatty acids produced by gut bacteria can disrupt the cells lining the gut.
This can lead to systemic inflammation, which has associations with increased amyloid protein in the brain.
Microbiota modification to reduce dementia risk
There is no cure for dementia, but there is a growing body of evidence that certain foods and nutrients may promote cognitive health.
The Alzheimer’s Society recommends a “diet rich in fruit, vegetables, and cereals, and low in red meat and sugar could help reduce dementia risks.”
They write that “[t]he best way to reduce your risk of dementia is to adapt various aspects of your lifestyle, including eating certain foods, taking regular exercise, not smoking, and maintaining normal blood pressure and cholesterol levels.”
“Research suggests that certain lifestyle choices […] can help reduce dementia risk. A good gut balance is achieved by eating a diet rich in fibrous, green, and leafy foods, getting adequate sleep, and consistent exercise,” Dr. Porter added.
Adherence to healthy dietary patterns such as the Dietary Approach to Stop Hypertension (DASH) and the Mediterranean-DASH diet Intervention for Neurodegenerative Delay (MIND) has associations with reduced cognitive decline and risk of Alzheimer’s disease.
Also, eating monounsaturated and polyunsaturated fatty acids and fish has links to reduced cognitive decline.
Dr. Saji echoed these findings, commenting that “[s]ome diet pattern[s] such as DASH, MIND, and a Japanese style diet could influence” the microbiome.
He also went on to claim that a “Japanese style diet has [a] causal relationship [with] dementia risk.”
Microbiota and the future
The exact mechanism of how the microbiome and its metabolites impact cognitive function is unclear. Research has highlighted conflicting results. What is certain is that people with dementia have different proportions of microorganisms within their microbiota.
Dr. Porter believes that “[u]nderstanding how a gut-derived inflammatory response combined with aging and a poor diet may contribute to the pathogenesis of Alzheimer’s disease might provide a unique therapeutic target in our fight against this disease.”
Extending the healthspan is a public health challenge, with diet being a factor that may prevent age-related diseases and preserve good health during aging.
Future treatments for cognitive decline and dementia may include changing the gut microbiota. Accumulating evidence says that dietary factors may be able to delay dementia. Although the mechanisms behind itare still not fully understood, small changes in diet may lead to a healthier future.
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