Polyphenolic Compounds: Orchestrating Intestinal Microbiota Harmony during Aging

Abstract

In the aging process, physiological decline occurs, posing a substantial threat to the physical and mental well-being of the elderly and contributing to the onset of age-related diseases. While traditional perspectives considered the maintenance of life as influenced by a myriad of factors, including environmental, genetic, epigenetic, and lifestyle elements such as exercise and diet, the pivotal role of symbiotic microorganisms had been understated. Presently, it is acknowledged that the intestinal microbiota plays a profound role in overall health by signaling to both the central and peripheral nervous systems, as well as other distant organs. Disruption in this bidirectional communication between bacteria and the host results in dysbiosis, fostering the development of various diseases, including neurological disorders, cardiovascular diseases, and cancer. This review aims to delve into the intricate biological mechanisms underpinning dysbiosis associated with aging and the clinical ramifications of such dysregulation. Furthermore, we aspire to explore bioactive compounds endowed with functional properties capable of modulating and restoring balance in this aging-related dysbiotic process through epigenetics alterations.

Keywords: aging; dysbiosis; epigenetics; intestinal microbiota; polyphenols.

Figure 1

Impact of aging on the composition of the intestinal microbiota. Significant changes in the intestinal microbiota composition arise from various stress factors linked to aging, resulting in a dysbiotic state. This imbalance entails reduced microbial diversity, fostering an uptick in opportunistic Gram-negative bacteria while decreasing species associated with health benefits. Furthermore, these shifts disrupt innate immunity, notably increasing antigen-presenting cells in the brain. Myeloid cell buildup reduces Akkermansia muciniphila, diminishing colonic mucus and heightening IL6-mediated inflammation. Additionally, alterations in tight junction expression (Zo-1 and occludin) contribute to changes in intestinal permeability [9,12,22,23,29,30,31,47,48].

Figure 2

Diseases associated with age promoted by dysbiotic condition. Changes in the intestinal microbiota during the aging process significantly impact health, heightening vulnerability to age-associated ailments such as neurodegenerative and cardiovascular afflictions, alongside conditions conducive to cancer development [4].

Figure 3

Benefits of polyphenolic compounds in modulating intestinal microbiota. Dysbiosis associated with aging promotes changes in the intestinal microbiota, leading to changes in the proportions of the Firmicutes/Bacterioidetes phyla, observed by the increase in the proportions of Pretovellaceae, Enterobacteaceae, and Enterococcus, and changes in the intestinal barrier mediated by the reduction in colonic mucus, favoring the development of the inflammatory process. However, the use of polyphenolic compounds confers health benefits mediated by the modulation of the intestinal microbiota, favoring an increase in the proportions of Fircumutes/Bacterioidetes, Bifidobacterium, and Lactobacillus, in addition to preventing inflammatory conditions, observed by the inhibition of inflammatory mediator genes such as p16, p21, IL1β, IL6, TNFα, Mcp1, and Cxcl1. Polyphenolic compounds favor the increase in the production of SCFA, such as butyrate, and the increase in colonic mucus, which plays an important role in protecting the intestinal barrier [194,195,197,202,203,204,205,206].