Your Gut Biome, Aging, and Neurodegenerative Disease

Last year, I published a post on this blog discussing the role of your gut biome in the development of mood and anxiety disorders. Since then, interesting research has emerged on the role of your gut biome in the development of neurodegenerative diseases such as Parkinson’s and Alzheimer’s.

These are exciting results, because they may contribute to finding ways to treat these tragic and irreversible diseases through manipulation of the gut environment. This post will discuss the role of the gut in immune function, and how changes occur in the microbiome with normal aging. A future post will discuss the relationship between the gut biome and neurodegenerative diseases.

The link between your brain and your gut is intimate, and it began long ago when you were just a bundle of primitive cells. In simple terms, immature cells develop into various types of organs and organ systems. Very early in the development of an embryo, a process called embryogenesis grows a temporary structure, the neural crest, that gives rise to your brain and spinal cord. The same primitive structure provides the cells that develop into the enteric nervous system, also called “the second brain.” These cells reside in the wall of your gut. There is a direct connection between your brain and your gut through a structure called the vagus nerve. Think of this as a major highway where traffic flows in two directions—from the brain to the gut, and from the gut back to the brain. The “traffic cops” that mediate the flow of information on this highway include the autonomic nervous system as well as sensory nerves and hormones.

Your gut environment is known as the biome. Humans possess as many bacterial cells as human cells—with over 10,000 species and trillions of microorganisms. The initial development of your microbial environment occurred when you were exposed to your mother’s microbiota during birth. Differences in newborn microbiomes occur depending on whether you were delivered vaginally or through a cesarean section. Your gut composition is relatively stable throughout your life and is unique to each individual.

Most people recognize the role of their gut in digestion and elimination, but did you know it plays a huge role in your immune function? In fact, 70% of your overall immune function lies in your gut. Therefore, it is not surprising that investigators have looked to the gut as a possible contributing factor in diseases involving inflammation and immune dysregulation.

Your immune system consists of groups of cells, proteins, and organs that work together to protect your body from germs, viruses, fungi, and pathogens. Immune cells act as your body’s first line of defense—they recognize, identify, and neutralize any detrimental substances (environmental or pathogenic) that may invade your body and cause you harm.

A well-balanced gut biome contributes to a healthy immune system. However, changes in the gut environment can lead to a situation called dysbiosis—imbalance in the gut microbial community that is associated with disease. How does this happen?

There are many factors that contribute to a healthy gut biome. Some of us are lucky to hit the genetic lottery from our parents. Heredity influences the makeup of your gut as do your dietary choices and lifestyle. However, in spite of this, dysregulation can occur in the following ways:

• Dietary changes that include an increase in protein, sugar, or food additives (preserved foods).
• Drinking alcohol in excess—generally two or more servings per day every day.
• Poor dental hygiene: untreated dental disease can lead to an overgrowth of unhealthy bacteria that can permeate your gut.
• Antibiotic use: in addition to treating offending pathogens, antibiotics can kill the good bacteria in your gut leading to an overgrowth of harmful ones. Taking probiotics can mitigate the potential damage.
• High levels of stress leading to anxiety can weaken your immune system.
• The use of substances containing nicotine (including vaping).
• Normal aging.

Aging and Gut Function

Your gut microbiota gradually diversifies once you are introduced to solid foods as a baby and tends to remain quite stable throughout adulthood. However, after age 65, gut microbiota diversity generally begins to decrease, and the percentage of beneficial microbes declines. Instead, previously non-dominant, potentially inflammatory strains increase. This has implications for your immune system and has been linked to degenerative diseases that occur more frequently with older age.

These facts were supported by researchers at Cedar Sinai Medical Center in Los Angeles in a 2021 study that examined gut samples taken from patients ages 18 to 80 who were undergoing diagnostic endoscopies. Their results showed that aging was correlated with changes in gut bacteria. The older subjects had more species of bacteria that are linked to human pathogens and had an overall decrease in bacterial diversity.

However, not all of the changes that occur in your gut with older age are due to age itself. In the same study, researchers were able to determine the quantity of antibiotics taken by each of the study participants. They found the amount of antibiotics taken by each patient was positively linked to a divergence in their gut population This was irrespective of their chronological age. Patients with more underlying health conditions who had taken greater quantities of antibiotics over their lifetime had an increase in Klebsiella bacteria, which are linked to hospital-acquired infections.

In addition, the gut biomes of older adults who reside in different parts of the world are different. This is impacted by climate, traditions, and culture. A research study conducted in Japan looked at a group of seniors with an average age of 107 and found that their gut biome has a distinct makeup enriched with compounds that actually had antimicrobial properties.

In general, studies of individuals 100 years or older report that their microbiomes are very different than the average elderly population. They have more beneficial microbes that strengthen the gut lining and help to maintain a lean body mass.

Factors That Influence a More Robust Gut Biome in Older Individuals

• Diet: "You are what you eat" has special meaning when it comes to establishing a healthy gut biome throughout life and into older age. In addition to your genetic makeup, your physical environment (exposure to toxins), history of medication use, and diet play a large role in determining what kinds of microbes reside in your gut. A high-fiber diet leads to a process that results in the formation of short-chain fatty acids (SCFA). These acids create an unfavorable gut environment for potentially harmful bacteria. Recent research on SCFA looked at their wide-ranging effects on health, including their potential to stimulate immune cell activity, and maintain normal blood levels of glucose and cholesterol.

• Exercise: Moderate exercise has positive effects on the health of average athletes, such as a reduction in inflammation and an improvement in body composition. It also creates positive changes in the gut microbiota composition and in the microbial breakdown products produced in the gastrointestinal tract. Dr. Jacob Allen, a researcher at the University of Illinois published the results of his study in Medicine and Science in Sports and Exercise. His team recruited 32 adults who did not regularly exercise. Half of them were obese, half were normal weight. He assigned both groups to six weeks of gradually more intense exercise from 30-60 minutes three times per week. They were then instructed to stop exercising for six weeks. Blood and stool samples were recorded at three points in time; before training started, at the end of six weeks of training, and after six weeks of no exercise. The results showed after six weeks of exercise training all subjects had increased levels of healthy microbes that produce short-chain fatty acids. Following six weeks of no exercise, all participant gut environments had reverted to their initial status.
• Nicotine: Cigarette smoking and smokeless tobacco are associated with alterations in the gut biome. A study published in 2018 in the Journal of Clinical Medicine followed over 700 male volunteers who had either never smoked, used to smoke, or currently smoked. The researchers collected fecal samples of each participant at the time of their annual physical at a healthcare screening center. The researchers found that current smokers had a higher proportion of pathogenic bacteria in their gut compared with never-smokers and former smokers. However, the composition of gut microbiota between never and former smokers did not show significant differences. This suggests if smokers quit smoking, gut microbiota composition is likely to recover to pre-smoking status, which is very promising news.