As quantitative digesta flows were not measured here, we can only suggest that colonic microbiota proteolytic activity towards AP enzyme may have been probably higher in adult ATB offspring than in controls. The actual reasons for this are presently unknown. Globally, pneumonia is a major cause of morbidity and mortality in adults. According to recent estimates, lower respiratory tract infections, including pneumonia, are the fourth most common cause of death, and 1.9 million adults aged _15 years die from lower respiratory infections every year. Studies have shown that the risks of pneumonia and pneumonia-related death increase with age and are highest among the elderly, indicating that the pneumonia burden is growing in this era of global population aging. Japan is the most aged society in the world; 25% of the Japanese population was aged _65 years in 2013. Although Japanese people have universal access to high-quality medical care as a virtue of universal health insurance coverage, an increasing number of elderly people are suffering from pneumonia; the disease is now ranked as the third cause of death in the country. Elucidating the true burden and etiologic fractions is crucial for effective disease control programs; however, the epidemiology of pneumonia remains largely unknown in Japan. Adult pneumonia has a multi-factorial etiology. Streptococcus pneumoniae is the leading cause of adult community-acquired pneumonia throughout the world, but it has been declining in high-income countries as a result of the wide use of antibiotics and the introduction of pneumococcal vaccines. Meanwhile, non-pneumococcal pneumonia, particularly among elderly people, is gaining attention. SCH772984 aspiration is considered a major cause of pneumonia in the elderly. The spread of drug-resistant strains is an emerging problem; the risk of drug-resistant pneumonia is particularly high in cases of health care-associated pneumonia and hospital-acquired pneumonia. In addition to bacterial pathogens, respiratory viruses, including influenza and respiratory syncytial virus, play important roles in the development of pneumonia among the elderly. This variety of etiologies makes controlling pneumonia among the elderly challenging. However, despite improvements in microbiological diagnostic methods, the etiology of pneumonia has not been fully characterized in aged societies. This prospective multicenter surveillance of adult community-onset pneumonia covered four major islands in Japan. The study objectives were to establish the age group- and etiology-specific incidences of pneumonia at a population level and to estimate the burden of pneumonia in the entire Japanese adult population. Aspiration-associated pneumonia has been overlooked in current pneumonia control programs. Although previous studies have shown that this condition is common among hospitalized pneumonia patients, its burden has never been evaluated at the population level in the past. Aspiration-associated pneumonia is a multi-factorial condition observed in older people. Impaired swallowing and an abnormal cough reflex increase the risk of oropharyngeal aspiration; the aspiration of colonized pathogens and gastric acid causes lower respiratory tract infection and/or lung injury. Compromised immunity, comorbidity and changes in lung function in this age group underlie this condition and are associated with the high mortality. Nursing home residents are at high risk for aspiration, but HCAP and aspiration-associated pneumonia are not identical conditions. In fact, in our study, 25.4% of CAP and 64.3% of HCAP cases were associated with aspiration. Effective clinical management and preventive measures targeting aspiration-associated pneumonia remain underdeveloped. ATS guidelines recommend using β-lactam/β-lactamase inhibitors for this condition, but the management of recurrent and refractory cases is challenging. For prevention, oral hygiene care and dysphagia rehabilitation have been suggested for reducing the risk of aspiration pneumonia, but with limited supporting evidence. The burden of aspiration-associated pneumonia may further increase as the number of elderly people who require long-term care increases. Effective clinical and public health intervention measures are urgently needed. In the current study, S. pneumoniae was the leading single etiological pathogen and was associated with 20-28% of pneumonia, confirming previous reports. Recent studies in Japan have shown that the positivity of S. pneumoniae among CAP cases was 17% to 24%. According to a recent meta-analysis, the proportion of pneumococcal pneumonia among CAP cases was 26-28%. The proportion of pneumococcal pneumonia among all pneumonia cases is declining in high-income countries, reflecting the wide use of antibiotics and pneumococcal vaccines.