With the arrival of a super-aging society, preventing diseases and extending the healthy life expectancy of the elderly are essential for reducing medical costs. For two decades, the Nakanojo Study has investigated the relationship between habitual physical activity and the physical and mental health of elderly populations; and since 2014, this research has expanded to examine the health effects of gut microbiota and the intake of lactic acid bacteria by the elderly. Recent research has indicated that gut bacteria have a major impact on host health, although the mechanisms are not fully understood. However, an increasing number of reports suggest that lactic acid bacteria have a beneficial impact on health. Clinical studies have shown that Lacticaseibacillus paracasei YIT 9029 (LcS; formerly known as Lactobacillus casei strain Shirota) provides health benefits, such as intestinal regulation, infection prevention, stress relief, and improved sleep quality. Despite the daily consumption of approximately 10 million bottles of dairy products containing LcS in Japan, its health effects among the general population had not been adequately investigated. Therefore, the Nakanojo Study conducted a fundamental investigation of the temporal variability of gut microbiota among the elderly and the relationships among diet, lactobacilli intake, physical activity, and gut microbiota. It also assessed the impact of lactobacilli on the health of the elderly, focusing on gut microbiota stability, hypertension incidence, defecation status, and physical fitness.

Asia has diverse food cultures some of which are known to have health benefits. In this context, the gut microbiota of Asians has attracted much interest. To investigate the gut microbiota in various Asian countries, we have been conducting the Asian Microbiome Project (AMP) since 2009. In particular, the AMP has focused on the gut microbiota of children which must strongly reflect the food cultures of their countries. The results of these investigations have shown that the gut microbiota of children in East Asia and Southeast Asia can be respectively classified into a BB type, which has a high presence of Bacteroides and Bifidobacterium, and a P type, which has a high presence of Prevotella. However, the AMP study has also indicated that these characteristics are disappearing under the influence of recent globalization of diets. Moreover, the pattern of changes in the gut microbiota in developing countries varies, probably due to the difference in food situations in each country.

The host develops an acquired immune system primarily based on immunoglobulin A (IgA) to control the gut microbiota, which is essential for maintaining host health. The production of high-affinity IgA, which binds specifically to gut bacteria, requires the selection of germinal center B cells by T follicular helper cells (TFH cells) in Peyer’s patches. Foxp3+ T cells and PD-1 expressed on TFH cells regulate the number and function of TFH cells, thereby regulating the selection process of germinal center B cells in the Peyer’s patches and the production of IgA appropriate for controlling the gut microbiota. As a result, a symbiotic relationship between the host and the gut microbiota is formed through IgA. However, long-term stimulation of the gut microbiota induces cellular senescence in gut germinal center B cells, leading to dysregulation of the gut microbiota due to decreased IgA production and diversity, ultimately resulting in age-related dysbiosis of the gut microbiota. These studies have highlighted the potential health risks associated with the gut microbiota, which are critical for maintaining the host’s health, in aging.