Leaky gut in systemic inflammation: exploring the link between gastrointestinal disorders and age-related diseases

Global average life expectancy has steadily increased over the last several decades and is projected to reach ~ 77 years by 2050. As it stands, the number of people > 60 years currently outnumbers children younger than 5 years, and by 2050, it is anticipated that the global population of people aged > 60 years will double, surpassing 2.1 billion. This demographic shift in our population is expected to have substantial consequences on health services globally due to the disease burden associated with aging. Osteoarthritis, chronic obstructive pulmonary disease, diabetes, cardiovascular disease, and cognitive decline associated with dementia are among the most common age-related diseases and contribute significantly to morbidity and mortality in the aged population. Many of these age-related diseases have been linked to chronic low-grade systemic inflammation which often accompanies aging. Gastrointestinal barrier dysfunction, also known as "leaky gut," has been shown to contribute to systemic inflammation in several diseases including inflammatory bowel disease and irritable bowel syndrome, but its role in the development and/or progression of chronic low-grade systemic inflammation during aging is unclear. This review outlines current literature on the leaky gut in aging, how leaky gut might contribute to systemic inflammation, and the links between gastrointestinal inflammatory diseases and common age-related diseases to provide insight into a potential relationship between the intestinal barrier and inflammation.