Emerging Evidence on the Use of Probiotics and Prebiotics to Improve the Gut Microbiota of Older Adults with Frailty Syndrome: A Narrative Review.

BACKGROUND: The gut microbiota can impact older adults' health, especially in patients with frailty syndrome. Understanding the association between the gut microbiota and frailty syndrome will help to explain the etiology of age-related diseases. Low-grade systemic inflammation is a factor leading to geriatric disorders, which is known as "inflammaging". Intestinal dysbiosis has a direct relationship with low-grade systemic inflammation because when the natural gut barrier is altered by age or other factors, some microorganisms or their metabolites can cross this barrier and reach the systemic circulation. OBJECTIVES: This review had two general goals: first, to describe the characteristics of the gut microbiota associated with age-related diseases, specifically frailty syndrome. The second aim was to identify potential interventions to improve the composition and function of intestinal microbiota, consequently lessening the burden of patients with frailty syndrome. METHODS: A search of scientific evidence was performed in PubMed, Science Direct, and Redalyc using keywords such as "frailty", "elderly", "nutrient interventions", "probiotics", and "prebiotics". We included studies reporting the effects of nutrient supplementation on frailty syndrome and older adults. These studies were analyzed to identify novel therapeutic alternatives to improve gut microbiota characteristics as well as subclinical signs related to this condition. RESULTS: The gut microbiota participates in many metabolic processes that have an impact on the brain, muscles, and other organs. These processes integrate feedback mechanisms, comprising their respective axis with the intestine and the gut microbiota. Alterations in these associations can lead to frailty. We report a few interventions that demonstrate that prebiotics and probiotics could modulate the gut microbiota in humans. Furthermore, other nutritional interventions could be used in patients with frailty syndrome. CONCLUSION: Probiotics and prebiotics may potentially prevent frailty syndrome or improve the quality of life of patients with this disorder. However, there is not enough information about their appropriate doses and periods of administration. Therefore, further investigations are required to determine these factors and improve their efficacy as therapeutic approaches for frailty syndrome.

Prenatal stress induces long term stress vulnerability, compromising stress response systems in the brain and impairing extinction of conditioned fear after adult stress.

Stress is a risk factor for the development of affective disorders, including depression, post-traumatic stress disorder, and other anxiety disorders. However, not all individuals who experience either chronic stress or traumatic acute stress develop such disorders. Thus, other factors must confer a vulnerability to stress, and exposure to early-life stress may be one such factor. In this study we examined prenatal stress (PNS) as a potential vulnerability factor that may produce stable changes in central stress response systems and susceptibility to develop fear- and anxiety-like behaviors after adult stress exposure. Pregnant Sprague-Dawley rats were immobilized for 1 h daily during the last week of pregnancy. Controls were unstressed. The male offspring were then studied as adults. As adults, PNS or control rats were first tested for shock-probe defensive burying behavior, then half from each group were exposed to a combined chronic plus acute prolonged stress (CAPS) treatment, consisting of chronic intermittent cold stress (4 °C, 6 h/d, 14 days) followed on day 15 by a single session of sequential acute stressors (social defeat, immobilization, cold swim). After CAPS or control treatment, different groups were tested for open field exploration, social interaction, or cued fear conditioning and extinction. Rats were sacrificed at least 5 days after behavioral testing for measurement of tyrosine hydroxylase (TH) and glucocorticoid receptor (GR) expression in specific brain regions, and plasma adrenocorticotropic hormone (ACTH) and corticosterone. Shock-probe burying, open field exploration and social interaction were unaffected by any treatment. However, PNS elevated basal corticosterone, decreased GR protein levels in hippocampus and prefrontal cortex, and decreased TH mRNA expression in noradrenergic neurons in the dorsal pons. Further, rats exposed to PNS plus CAPS showed attenuated extinction of cue-conditioned fear. These results suggest that PNS induces vulnerability to subsequent adult stress, resulting in an enhanced fear-like behavioral profile, and dysregulation of brain noradrenergic and hypothalamic-pituitary-adrenal axis (HPA) activity.