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The age-related changes in the gut microbiota.

In the human intestine, there are hundreds of species and around 40 trillion bacteria, and since the establishment of gut bacterial analysis methods using next-generation sequencers, it has been found that factors such as the host’s age, health status, diet, exercise, and medication can influence changes in the gut microbiota. In particular, the host’s age has been shown to have a significant impact on the balance of gut microbiota, as demonstrated by several cohort studies.

During middle to old age, there are changes in the gut microbiota, such as a decrease in Bifidobacteria and an increase in Enterotoxigenic Bacteroides fragilis, which produces toxins. A study analyzing the gut microbiota of 367 Japanese individuals, ranging from newborns a few weeks old to healthy individuals aged 104, revealed that the proportion of Bifidobacteria decreases significantly after weaning and further decreases after the age of 60. Additionally, the proportion of Proteobacteria, which includes pathogenic bacteria such as Escherichia coli and Salmonella, increases notably from the 60s.

These changes in the gut microbiota of older adults are believed to be influenced by various age-related changes in the body, such as reduced chewing and swallowing abilities, decreased secretion of gastric acid and bile acids, and weakened immune function, all of which are important age-related changes in the host’s body.

For example, the oral cavity contains approximately 10^9 oral bacteria per 1 mL, and by swallowing about 600 mL of saliva per day, approximately 10^11 bacteria pass through the digestive tract. While most of these bacteria are eliminated by stomach acid, a decrease in stomach acid secretion due to aging could potentially increase the number of live bacteria reaching the lower gastrointestinal tract.

Indeed, studies have confirmed that the similarity between the oral and gut microbiota is significantly higher in older adults compared to healthy adults in various trials. Moreover, Fusobacterium nucleatum, associated with periodontal disease, has been detected more frequently in the gut microbiota of colorectal cancer patients, suggesting a possible transition from the oral cavity to the intestine.

Epidemiological analysis has shown that periodontal disease is a risk factor for various conditions, highlighting the importance of oral care in older adults as a preventive strategy for age-related diseases.

The increase in Proteobacteria and Fusobacteria with age is known to induce an inflammatory response through lipopolysaccharides (LPS) produced by these bacteria, leading to a decrease in intestinal barrier function. This could result in Leaky Gut, allowing bacterial components to leak into the bloodstream, promoting chronic inflammation and age-related diseases.

On the other hand, Bifidobacteria play beneficial physiological roles by producing lactic acid and acetic acid. For instance, acetic acid increases the expression of tight junction-related factors such as Claudin-1 and Occludin in intestinal epithelial cells, enhancing intestinal barrier function. Acetic acid also exhibits strong bactericidal activity, suppressing the growth of Escherichia coli and promoting a healthy gut environment.

Supercentenarians (those aged 100 or older) have been reported to have a higher proportion of Bifidobacteria in their gut microbiota. In fact, Bifidobacteria isolated from the gut microbiota of supercentenarians have been shown to enhance gut immune barrier function in experiments using mice.

Based on these findings, the use of probiotics and prebiotics to maintain and increase Bifidobacteria, which decrease with age, has been suggested as a beneficial approach for preventing age-related diseases and promoting anti-aging effects.

Dr. Munenori Matsuzawa, Chief Medical Officer, Aoyama Medical Clinic.

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