Functional deficits of the intestinal microbiota in the elderly

Research conducted on aging and health has significantly increased life expectancy, however, the period of life lived in good health has remained relatively constant. Consequently, the focus of medical and health research has shifted from simply extending life expectancy and seeking longevity to slowing down the aging process and preventing morbidity. The gastrointestinal tract and microbiota are significantly impacted by age, affecting nutrient absorption, inflammation, and immune function. Age-related changes in the microbiota influence immune function, inflammation, and mental health. The thesis explores the effects of age on the intestinal microbiome using the IAE cohort and further analyzes the effects of the microbiota on the mental health of older adults using the EE cohort. We identified a functional core of 140 crucial KO categories, from those 35 were further analyzed as they are exclusively produced by bacteria and were considered important in the host metabolism. The selected KO categories were analyzed using metaproteomic, metagenomic, metatranscriptomic, and metabolomic data, these KOs included pyruvate metabolism, arginine-related functions, folate metabolism, essential amino acids, and fucose synthesis. These functions are essential for energy production, neurotransmitter regulation, genetic stability, protein synthesis, and immune function. Furthermore, we identified 48 KO categories present in infants and adults but absent in the elderly. From these, we selected a total of 13 KOs that are exclusive from bacteria and that are involved in age-related diseases and analyzed them using metaproteomic, metagenomic, and metatranscriptomic techniques. Functions related to glucose and pyruvate metabolism, B complex vitamins, tryptophan, inflammation, secondary bile acids, and methane metabolism are crucial in early life and are lost during aging. Aging may lead to a decline in energy production, nutrient absorption, immune regulation, and gut health. Finally, we studied the impact of mental health medication on the microbiota in the elderly. Mental disorders, affecting mood, cognition, and behavior, have a high prevalence among the elderly. Significant differences in the intestinal and oral microbiota composition are found, especially in genera involved in tryptophan, arginine, GABA metabolism, and inflammatory processes. Functional analysis reveals differences in KO categories related to tryptophan and arginine metabolism, along with 29 pathways, including those related to longevity, dopaminergic and serotoninergic synapses, and amino acids. This thesis shows that functions involving the metabolism of pyruvate, glucose, neuroactive compounds (polyamines, GABA, tryptophan), and B-complex vitamins decline with age. This decline may be implicated in the aging process, age-related diseases, and the decline in mental health.

Conselleria de Innovación, Universidades, Ciencia y Sociedad Digital de la Generalitat Valenciana