How does the microbiota change with age and disease? Why does it matter?

Healthy eating, exercise and a positive mood are thought to have a beneficial effect on our microbiota. A healthy microbiota will also help reduce the risk of many chronic diseases that develop in later life. So, how do factors such as older age, diet and lifestyle affect the microbiota? Let’s explore the answer to this question together.

Microbiota are harmless microorganisms found in the human body, mainly in the gut and on the skin. There are more microorganisms than human cells in the body, but because they are much smaller in volume, the microbiota account for only one part in 50-100 of human body weight.

Age, disease status and diet, in particular, can have a significant effect on gut microbiology, and many scientific studies show that the foods consumed can cause substantial changes in the microbiota. The bacteria in the flora include beneficial and harmful bacteria in certain proportions. When the beneficial-to-harmful bacteria ratio decreases, a pathological process called “microbial dysbiosis” begins.

In the early years of life, the nature of the microbiota is more stable. As age advances, however, situations may arise in which this stability is lost and age-related dysbiosis begins to develop. This is not related only to chronological age, the number of years lived. It is also closely related to biological age, or physiological age. In other words, being middle-aged alone is not sufficient for a person to develop dysbiosis. A person’s diet and lifestyle are among the most fundamental factors affecting gut health.

How does the aging microbiota change?

There are conflicting views about whether gut function is affected by age. However, a substantial body of scientific evidence from animal studies shows that gut function declines with age. The diagram below shows age-related changes in the microbiota arising from physiology, lifestyle and health status.

Figure: Changes in the aging microbiota: Age-related changes in the microbiota arise from physiological, lifestyle and health factors. Each of these factors is associated with changes in the relative abundance of certain members of the microbiota. Some behavioral, metabolic and physiological mechanisms that may explain the observed increases or decreases are listed.

The relationship of disease, inflammation and older age with the microbiota

Inflammation, the immune system’s response while trying to protect organs from infection and injury, can also adversely affect the microbiota. Inflammation can develop as a result of many diseases and may also arise with advancing age. Older age is characterized by chronic and metabolic health problems and an increased concentration of inflammatory markers in the bloodstream. The term “inflammaging” is even used for this situation. (“Inflamm-aging” combines the English words “inflammation” and “aging”.) Low-grade inflammation may be associated with age-related decline in many functional systems. For example, studies in mice show that mucin production in the gut decreases with age, causing the mucus layer to become thinner. Reduced mucin production may be associated with increased inflammatory responses. This relates to mucin’s protective effect in the digestive system, preventing microbes from coming into direct contact with epithelial cells. When the mucin layer is lost, microbes can easily reach the epithelial layer, potentially causing an inflammatory response. Mucin is also a good food source for bacterial strains. However, the inflammatory response in the gut is not always related to changes in the microbiota, nor are changes in the microbiota related only to age. Changes in the microbiota and inflammatory response can occur as a consequence of many conditions. In disease states, bacterial strains in the microbiota may increase or decrease. Let’s examine the diagram below together for more detail on the disease–microbiota and aging–microbiota relationships;

In contrast to the relationship between older age and the microbiota, the microbiota changes seen in frailty syndrome are associated more closely with biological aging than chronological age (calendar age). Frailty syndrome is defined as a reduced physiological response to stress resulting from a decline in bodily functions due to biological aging. The most prominent feature of the microbiota of people with frailty syndrome is loss of diversity. This can arise for many different reasons, including inability to eat healthily, inability to exercise because of health status, inflammation, prolonged hospital stays and long-term use of drugs such as antibiotics. Insufficient consumption of fiber-rich foods is thought to be the most important factor in diet-related reductions in microbiota diversity. Studies show that short-chain fatty acids (SCFAs) decrease in people with frailty syndrome. SCFAs are organic acids produced by gut bacteria through the fermentation of carbohydrates and fiber. SCFAs with many important benefits for gut and general health include acetate, butyrate and propionate. However, the most beneficial and important fatty acid is butyric acid. Patients with low SCFA levels have impaired gut barrier function and increased intestinal permeability.

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Centenarians (people aged 99-104) and semi-supercentenarians (people aged 105-109) have a biological age younger than their chronological age. This is thought to be the secret of their longevity. Studies of centenarians and semi-supercentenarians suggest that various bacterial families in their microbiota have positive effects on their general health, thereby extending their lives. Healthy lifestyle and eating habits are also thought to contribute to a younger biological age. In particular, Lachnospiraceae, Ruminococcaceae and Akkermansia are the families in which increased strain abundance is associated with longevity. Fiber from healthy foods such as fruit, vegetables, legumes and whole grains is thought to be the factor that increases microbiota diversity the most in long life.

- Related topic: How much dietary fiber should we consume?

Summary & Commentary

Scientific studies support a decrease in beneficial bacteria in the gut microbiota in disease states. Biological aging is also thought to affect the gut microbiota more than chronological aging. The increase in beneficial bacteria, particularly Lachnospiraceae, Ruminococcaceae and Akkermansia, in the guts of semi-supercentenarians and centenarians supports this view. This is because these people have a high chronological age but a younger biological age. We can say that one of the most important elements of a healthy microbiota is a healthy, balanced dietary pattern rich in fiber. To contribute to both general health and gut health, we recommend regular exercise, drinking enough water and following a balanced, healthy, fiber-rich dietary pattern such as the Mediterranean Diet.