Gut microbiota changes in the extreme decades of human life: a focus on centenarians

Abstract

The gut microbiota (GM) is a complex, evolutionarily molded ecological system, which contributes to a variety of physiological functions. The GM is highly dynamic, being sensitive to environmental stimuli, and its composition changes over the host’s entire lifespan. However, the basic question of how much these changes may be ascribed to variables such as population, diet, genetics and gender, and/or to the aging process per se is still largely unanswered. We argue that comparison among studies on centenarians—the best model of healthy aging and longevity—recruited from different geographical areas/populations (different genetics and dietary habits) can help to disentangle the contribution of aging and non-aging-related variables to GM remodeling with age. The current review focuses on the role of population, gender and host genetics as possible drivers of GM modification along the human aging process. The feedback impact of age-associated GM variation on the GM–brain axis and GM metabolomics is also discussed. We likewise address the role of GM in neurodegenerative diseases such as Parkinson’s and Alzheimer’s, and its possible therapeutic use, taking advantage of the fact that centenarians are characterized by an extreme (healthy) phenotype versus patients suffering from age-related pathologies. Finally, it is argued that longitudinal studies combining metagenomics sequencing and in-depth phylogenetic analysis with a comprehensive phenotypic characterization of centenarians and patients using up-to-date omics (metabolomics, transcriptomics and meta-transcriptomics) are urgently needed.

Remitted affective disorders and high familial risk of affective disorders associate with aberrant intestinal microbiota

“…Our study has several limitations. The relative composition of the intestinal microbiota is unique in each individual with multiple influencing factors including diet, medication, age, and sex . The gut microbiome differs across humans and family members and individuals living together seem to have more similar microbiota than unrelated individuals.…”

Aging and Alzheimer’s disease: Comparison and associations from molecular to system level

“…In a study of female identical twins, frailty as measured by Rockwood Frailty Index has been found to be negatively associated with gut microbiome diversity (Jackson et al, 2016). Among centenarians, the best model of “successful” aging, their gut microbiome showed high diversity of species composition compared to younger elderly adults (Santoro et al, 2017). A recent study even found that when maintained under germ‐free conditions, mice do not display an age‐related increase in circulating proinflammatory cytokine levels (Thevaranjan et al, 2017); thus, inflammaging is controllable in an animal model.…”

Bacteria in the ageing gut: did the taming of fire promote a long human lifespan?

“…For example, Bilophila wadsworthia bacteria are often viewed as pathogens because their presence correlates with inflammatory bowel disease (Devkota et al ., ). By contrast, they are also a positive marker of extreme longevity (Salazar et al ., ; Santoro et al ., ). This disparity in their role, related to abundance of Bilophila strains in the distal gut, is reflected in a variety of situations.…”

“…The presence of specific butyrate producers appeared to be correlated to extreme longevity. Interestingly, the species that are involved in this metabolism are not the same ones as those of younger subjects (Hippe et al ., ; Santoro et al ., ). Several key species have been proposed to be particularly important at old age, but it is somewhat difficult to identify functional criteria that would lead to causal relationships between the presence of a species and a long lifespan.…”