Age-related diseases, therapies and gut microbiome: A new frontier for healthy aging
Introduction
It is now a fact that the gut microbiota, i.e., the community of over 10 trillion microorganisms dwelling in our intestine, is a lifelong companion that actively and sometimes decisively contributes to our health (Turroni et al., 2018). Among the main drivers of its variation, there are a series of factors including minimally genetics and mostly variables related to the exposome, such as outdoor and occupational exposures, built environment, socio-economic factors, food and water contaminants, drugs and other aspects related to personal behavior, e.g., diet, lifestyle, physical activity, smoking, alcohol use, etc. (Deschasaux et al., 2018, He et al., 2018, Rothschild et al., 2018, Vujkovic-Cvijin et al., 2020). It is therefore not surprising that the gut microbiome predictably changes its compositional and functional profile from infancy to old age, following a sort of developmental trajectory along our life, parallel to major changes in the aforementioned variables (Kundu et al., 2017). Despite these changes, the microbiome continues to act as an ecosystem service provider, responding to precise physiological needs at different stages of life, at least until the microbiome-host relationship begins to crack due to progressive physiological changes in old age (Claesson et al., 2012). In this regard, the debate is still open on whether variations in the gut microbiome in elderly subjects are to be considered dysbiosis or adaptation to aged conditions, also considering the recent identification of potential longevity signatures in the microbiome profile (Biagi et al., 2017). On the other hand, it is known that imbalances in the gut microbiome can contribute to the onset and progression of disorders (and response to treatment), throughout our life, including those related to age, such as frailty, cardiovascular disease, and neurodegenerative diseases (such as Alzheimer and Parkinson) (Bosco and Noti, 2021, Buford, 2017). In this context, clinical intervention trials are accumulating that aim to explore the impact of microbiome modulation (or rejuvenation) on age-related decline in the musculoskeletal, cardiometabolic and nervous systems.
In this narrative review, we first summarize the state of the art on adaptive/maladaptive changes in the gut microbiome over age, up to the extreme limits of human life, and then discuss the potential involvement of the microbiome in age-related disorders, namely frailty and neurodegenerative diseases (i.e., Alzheimer and Parkinson), as well as hypertension and cardiovascular disease, as risk factors for the onset and acceleration of disability, and Down syndrome, as an example of accelerated aging. Particular attention will be paid to the bidirectional relationship between microbiome and anti-age-related disease therapies, and to the sometimes decisive effects on pharmacokinetics, side effects and drug response. Finally, we comment on the clinical trials that up to now have been designed to counter the age-related decline of the musculoskeletal system, mental and metabolic health, by restoring eubiotic profiles of the gut microbiome through prebiotics, probiotics, synbiotics and even fecal microbiota transplantation. While no results are yet available, the need to preserve our microbial counterpart for healthy aging and hopefully as the key to achieving longevity is increasingly evident. See Fig. 1 for a summary of the role of the gut microbiome in age-related disorders, including response to commonly prescribed medications, and the available microbiome manipulation tools that could help improve overall symptoms in the aging population.
Section snippets
Gut microbiome changes along aging
As mentioned above, the gut microbiome evolves with us throughout life. Of course, it is unclear whether its changes merely reflect secondary biological processes occurring at distinct life phases or whether it contributes to at least some age-related transitions, but its dynamics along aging are deemed increasingly worthy of further research for translations into clinical practice aimed at improving the health of elderly people. In this chapter, the main milestones of gut microbiome research
Gut microbiome dysbiosis in age-related diseases
Based on the above, it is not surprising that alterations in the gut microbiome have been shown to contribute to the onset and progression of numerous diseases throughout our lives, not just intestinal (Duvallet et al., 2017). Below we summarize the main changes observed in the composition and functionality of the microbiome in the context of age-related diseases, with particular regard to frailty, neurodegenerative diseases (such as Alzheimer and Parkinson), as well as hypertension and
Anti-age-related disease therapies and gut microbiome: a two-way relationship
The various chronic diseases that arise with increasing age (as discussed in the previous paragraphs) often involve taking multiple drug therapies, which can impact on the gut microbiome as well (Falony et al., 2016, Jackson et al., 2018, Maier et al., 2018), with potentially significant repercussions on the host health. On the other hand, there is a growing awareness of the role of the microbiome in influencing the fate and therefore the efficacy of drugs (Barone et al., 2021b, Klunemann et
Microbiome-based intervention strategies to combat aging and age-related diseases
Based on the above, it is not surprising that the gut microbiome is considered a strategic therapeutic target in the context of multiple disorders, including those related to age (Duvallet et al., 2017, Flanagan et al., 2020, Wilson and Nicholson, 2017). The development of microbiome-tailored intervention strategies aimed at restoring and maintaining a health-associated layout is indeed gaining increasing attention in the field of healthy aging, to address the specific needs of the elderly
Conclusions
The extension of lifespan on a global level does not always correspond to an equally positive healthspan. This trend has led to a growing need to identify new intervention strategies aimed at reducing the burden of age-related diseases, exerting overall geroprotective effects. In recent years, the fascinating role of the gut microbiome has emerged as a key contributor to host physiology and various pathological conditions, including those associated with the aging process. In this scenario,
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Declaration of interest
None.
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