Editors' ChoiceAging

Better living through your gut microbes

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Science Translational Medicine  14 Aug 2019:
Vol. 11, Issue 505, eaay7700
DOI: 10.1126/scitranslmed.aay7700

Abstract

Correcting gut microbial dysbiosis improves health and life span in a mouse model of accelerated aging by restoring intestinal bile acid and small-molecule metabolite balance.

The human gut microbiome and its composition is increasingly recognized as having significant association with several diseases and with response to certain drug treatments. However, less is known about the contribution of the microbiome to aging, and how and whether microbiome composition differences are associated with longevity and overall health. One limitation has been the lengths of time necessary to study such changes, particularly in humans. To address this, Barcena et al. investigated the role of intestinal dysbiosis in aging in mouse models and by comparing the microbiota of humans with accelerated aging syndromes, primarily Hutchinson-Gilford progeria syndrome (HGPS), with that of human centenarians. Progeroid syndromes, characterized by premature aging-related diseases and reduced life span, have been associated with several genetic mutations, the most well known being HGPS, which is caused by mutations in the nuclear envelope protein lamin A gene (LMNA).

To elucidate the composition and diversity of the microbiome in HGPS, the authors examined the microbiome of HGPS mouse models and human patients and found marked dysbiosis compared with age-matched controls or human centenarians. They hypothesized that gut microbiota changes associated with the accelerated aging phenotype seen in the HGPS mice. To confirm this, the authors performed fecal microbiome transplantation (FMT) from wild-type to HGPS mice and found that the microbiome from wild-type mice improved health markers and increased overall life span in the HGPS mice. In particular, transplantation of Akkermansia muciniphila alone resulted in a modestly increased life span. Metabolic profiling of the intestinal contents of these mice revealed an enrichment in secondary bile acid biosynthesis and small-molecule metabolites (arabinose, ribose, inosine) in both wild-type mice and HGPS mice that had received FMT, leading the authors to conclude that one effect of FMT may be to restore intestinal bile acid and metabolite balance.

This work suggests a connection between aging, the gut microbiome composition, and bile acid metabolism, and provides additional evidence that microbiome modulation through FMT could provide some protection against age-related disease. Further studies, including well-designed controlled trials, will be necessary to confirm whether FMT could provide such protection and further elucidate the molecular and metabolic mechanisms that underlie the improvements in health and life span described here.

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