Martina Morandi MicrobiotaMi

MicrobiotaMi Comment 29_21  by Martina Morandi

Related Journal Article:  Gut microbiome pattern reflects healthy ageing and predicts survival in humans.

This article was published in the:  Nat Metab 3, 274–286 (2021). https://doi.org/10.1038/s42255-021-00348-0

Gut microbiota a key player in healthy aging

Extrinsic factors, such as lifestyle, diet, medication, physical activity, are essential in the control of human healthy aging and they can have a significant impact on gut microbiota. The latter is not a static entity, but it changes throughout the lifespan becoming increasingly unique to individuals with age. Several studies have investigating the gut microbiota of centenarians and supercentenarians showing that even if the core taxa (i.e., Bacteriodetes, Firmicutes, Verrucomicrobia) are depleted in their abundance, the α-diversity increased. This phenomenon can help to understand how gut microbes reflect healthy aging.

In this study published on Nature Metabolism, Wilmanski and colleagues analysed the gut microbiota and phenotypic data of over 9000 individuals from 3 independent cohorts: the Arivale cohort (18-87 years), the Osteoporotic Fractures in Men (MrOS) cohort (78-98 years), and the American Gut Project (AGP) dataset (18-101 years), a self-selected citizen-scientist cohort of thousands of individuals.

They started to identify gut microbiome aging patterns across most of the adult human lifespan, analysing baseline data taken from the Arivale cohort and subsequently from MrOS cohort, in which detailed health metrics and follow-up data on mortality were provided. In this way, it was easier to identify the correlation between the patterns found in the Arivale cohort and data on health and survival in the later decades of human life.

To perform the analysis, they used the Bray-Curtis uniqueness measure, a weighted measure not influenced by phylogeny and optimal to capture changes in gut bacteria dominance. Between all the factors tested – clinical laboratory tests, demographic information, self-reported lifestyle/health measures – age has demonstrated to be the strongest association with gut microbiome uniqueness. However, after adjusting only for age, a significant association emerged between healthier metabolic and lipid profiles and individuals with more unique gut microbiomes.

To better understand the involvement of host physiology in determining the unique composition of gut microbiota in aging, the researchers had evaluated the plasma metabolome in the Arivale cohort. They observed that the distinct shift in gut microbial aminoacid metabolism was in line with the more unique gut microbiome profiles, indicating the metabolome as a possible biomarker to predict changes in gut microbiota across the human lifespan.

Further analysis in the Arivale, MrOS and AGP cohorts were conducted in order to identify individual taxa with gut microbiome uniqueness. Data showed a correlation between rising uniqueness with age and the rise and the decline of the same sets of taxa across considerably diverse population. This association was lower or absent in those individuals with worse health, compared with the healthier ones.

Next, they performed abundance analysis in the MrOS dataset to identify genera associate with age in healthy individual and, only Bacteroides showed a significant negative association with age, indicating that the feature of unique microbiomes is the depletion of the most common and dominant genera. Moreover, in all the individuals in the cohort, they found a positive association between relative Bacteroides abundance and increased risk off all-cause mortality.  In particular, in those individual aged +85 years, the mortality risk decreased where more unique gut microbiomes were found.

To conclude, this study shed light on the correlation between compositional uniqueness of the gut microbiome and healthy aging, which is characterised by gradual shifts in gut metabolic capacity, revealed by plasma metabolome analysis. The identification of aging patterns within the gut microbiota, might represent a clinical implication in monitoring and modifying gut microbiome throughout the human lifespan.

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