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Age-specific microbiota in altering host inflammatory and metabolic signaling and metabolome based on sex.

HepatoBiliary Surg Nutr 2022;11(2):305-307 | https://dx.doi.org/10.21037/hbsn-2022-04 We read the recent study, “Age-specific microbiota in altering host inflammatory and metabolic signaling as well as metabolome based on the sex”, published in Hepatobiliary Surgery and Nutrition about the effects of sex-dependent changes in gut microbiota on age-related metabolic disease (1). The authors examined the relationships between fecal microbiota and age-dependent metabolic phenotypes in both sexes and demonstrated the efficacy of fecal microbiota transplantation (FMT) in altering insulin sensitivity depending on the sex of the recipients. Aging is considered a state of low-grade inflammation without clear etiological factors, and is accompanied by many age-associated pathologies, including both gastrointestinal and non-gastrointestinal pathological diseases, such as metabolic issues (2). In the study, the authors observed that aging increased the expression of inflammatory signaling and reduced the expression of metabolic signaling and insulin sensitivity in both sexes. Age-associated inflammation is an important risk factor for overall mortality in older adults. Individuals with higher than age-average levels of inflammatory markers are more likely to have a variety of diseases (3). Despite the clinical importance of age-related inflammation, the etiology responsible for its development has not yet been identified. The human gut microbiota is a complex ecosystem harboring trillions of microbiota whose number is somewhere between 10 and 10 (4). Microbes are established from birth and become more diverse and variable with advancing chronological age (5). Many studies have shown that the gut microbiota is not only involved in human physiology but also affects host immune regulation and metabolism and regulates local or systemic inflammation (6,7). It has been reported that aging and age-related metabolism in humans is associated with the composition and diversity of intestinal microbiota (8). Cross-sectional studies of fecal samples from individuals in different age groups suggest that gut microbiota in adults is highly individual and specific (9). With advancing chronological age, overall richness decreases, and a certain group of the gut microbiome has been identified in the elderly populations associated with frailty increases. This change may be related to the deterioration of the intestinal mucosal barrier and chronic low-grade inflammation in the elderly. Growing data showed that the age-related changes in the microbiota led to increased permeability in the colon and caused inflammatory response, further affecting metabolic diseases (10,11). In Drosophila intestinal epithelial cells, a dysregulated proliferation of intestinal stem cells increases with aging with the loss of the selectively permeable intestinal barrier, leading to increased infection and mortality (12). Transferring gut microbiota from aged mice to young germ-free mice triggers innate immune and inflammatory responses similar to “inflammation” (13). Age-related inflammation and dysbiosis of the microbiota drive gut permeability and increase levels of inflammatory mediators in circulation (14). In the article, the authors observed that aging reduces glucose and lipid metabolism regulators, such as sterol-regulatory element binding protein-1C, fatty acid synthase, and Cyp4a10, which suggested abnormal glucose and lipid metabolism. The mitochondrial biogenesis-related genes, such as silent Editorial