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The gut microbiome as a modulator of healthy ageing

Nature Reviews Gastroenterology & Hepatology volume 19, pages 565–584 (2022)Cite this article

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Abstract

The gut microbiome is a contributory factor in ageing-related health loss and in several non-communicable diseases in all age groups. Some age-linked and disease-linked compositional and functional changes overlap, while others are distinct. In this Review, we explore targeted studies of the gut microbiome of older individuals and general cohort studies across geographically distinct populations. We also address the promise of the targeted restoration of microorganisms associated with healthier ageing.

Key points

  • The gut microbiome is a transducer of environmental signals, modifies the risk of disease across all age groups and changes with host age.

  • Age-related alterations in the gut microbiome are influenced by personal factors, including progressive physiological deterioration, as well as by lifestyle-linked factors such as diet, medication and reduced social contact.

  • Age-related and disease-related deterioration in the gut microbiome of older people reflect overlapping interactive but distinct processes.

  • Resetting gut microbiome-derived signals of ‘unhealthy’ ageing through personalized or subpopulation-level microbiome-associated interventions is a new area of research informed by large shotgun metagenomics-based studies and data analytics.

  • Gut microbiome-based therapeutics for older people will need combined approaches, including dietary intervention with microbial restoration of lost strains.

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Fig. 1: Microorganism–host signalling as a contributor to healthy or unhealthy ageing.
Fig. 2: Physiological, social and disease-related influences on the microbiome of older people.
Fig. 3: Microbiome alterations in ageing (and unhealthy ageing).
Fig. 4: Functional implications of microbiome alterations on host physiology in ageing.
Fig. 5: Microbiome-associated interventions to prevent unhealthy ageing.
Fig. 6: Strategies for the formulation of personalized microbiome reconstruction strategies in older people.

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Authors and Affiliations

  1. APC Microbiome Ireland, University College Cork, National University of Ireland, Cork, Ireland

    Tarini Shankar Ghosh, Fergus Shanahan & Paul W. O’Toole

  2. School of Microbiology, University College Cork, National University of Ireland, Cork, Ireland

    Tarini Shankar Ghosh & Paul W. O’Toole

  3. Department of Medicine, University College Cork, National University of Ireland, Cork, Ireland

    Fergus Shanahan

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All authors contributed equally to all aspects of the manuscript.

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F.S. is a cofounder of three campus companies: Alimentary Health Ltd, Tucana Health Ltd (now named 4D Pharma Cork) and Atlantia Food Clinical Trials. P.W.O.T. is a cofounder of 4D Pharma Cork. T.S.G. declares no competing interests.

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Glossary

Probiotics

Microbial species (or lineages) that have a beneficial effect on the host.

Psychobiotics

Subgroup of probiotic bacteria that have a beneficial impact on the gut–brain axis resulting in improved behaviour or cognitive function.

Internal transcribed spacer

A method of microbial community profiling similar to 16S profiling that relies on specific PCR-based amplification, sequencing and characterization of the internal spacer DNA regions between the small subunit rRNA components (16S for bacteria/archaea and 18S for eukaryotes) and the large subunit rRNA components, and is typically used for the characterization of the mycobiome of a given environment due to the superior phylogenetic granularity afforded by the sequence.

Inter-study variations

Variations in the patterns of gut microbiome alterations detected across different studies investigating the same (or similar) host trait or phenotype (for example, age, BMI, a disease or disorder, or specific dietary patterns).

Shotgun metagenomics

A method of community genomic profiling that involves the extraction and sequencing of the entire genomic content of all cells belonging to a given microbial community.

Prebiotic

Nutritional supplements designed to increase the abundance of specific target groups of beneficial microorganisms based on restricted catabolic ability in certain taxa.

Synbiotics

Single or consortia of beneficial microorganisms that are administered in combination with prebiotics.

Postbiotics

Deliberately inactivated (heat-killed) microbial cells, cell components or microbiota-derived metabolites that confer health benefits.

Quantitative polymerase chain reaction

(qPCR). A method of real-time microbial quantification in a given sample that relies on measuring the change in PCR amplicon copy number (in this context, amplified by primers designed against a phylogenetic marker gene corresponding to a given species or a microbial group) during the cycles of the PCR; copy numbers of phylogenetic marker gene regions belonging to microbial lineages in higher abundance are expected to be amplified faster, resulting in a faster increase in the strength of fluorescent oligonucleotide probes targeted at these lineages.

Fluorescence in situ hybridization

(FISH). A method of physically locating or enumerating the population of a specific microorganism or cell type by using fluorescent oligonucleotide probes that bind to specific genomic sequences in the target cells with high sequence complementarity; it can be used to measure either specific bacterial species or overall bacterial cell abundance (by using probes towards the universally conserved regions of the 16S rRNA gene).

16S profiling

(Also known as 16S rRNA sequencing). A method of microbial community profiling that relies on specific polymerase chain reaction (PCR)-based amplification, sequencing and phylogenetic profiling of either the full length or specific sub-regions of the 16S rRNA marker gene across all bacterial and archaeal cells present in a given sample.

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Ghosh, T.S., Shanahan, F. & O’Toole, P.W. The gut microbiome as a modulator of healthy ageing. Nat Rev Gastroenterol Hepatol 19, 565–584 (2022). https://doi.org/10.1038/s41575-022-00605-x

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