Researchers here provide evidence for detrimental changes in the composition of gut microbiota, and thus the compounds they secrete, to occur quite sharply at a threshold age as early as mid-30s. It is well known that the microbial populations of the gut change with age, and there are several identified mechanisms by which compounds secreted by beneficial gut microbes improve health over the long-term, or by which harmful gut microbes can spur chronic inflammation. It has been suggested that supplementation with some of these secreted compounds might be useful, or engineering of the microbial population to minimize harmful microbes and expand beneficial species.
Here, we have compared the proteins associated with the active fraction of the microbiota in infants, adults and elderly individuals. Ageing is associated with the progressive activation of gut bacteria, possibly because bacteria must react to increasing number of factors associated with preserving the health status in response to exposure to an increasing number of environmental conditions that are distinct and greater than the conditions experienced during early life stages. Most importantly, we identified a link between ageing and the microbial pathway associated with tryptophan and indole production and metabolism by the commensal microbiota. The key proteins involved in tryptophan-to-indole metabolism, TnaA and TrpB are both more abundant and expressed in the gut microbiota of infants. Both were expressed at significantly lower levels in adults and at even lower levels or below the detection limit in elderly individuals.
As shown in a recent study, indoles from commensal bacteria extend the healthspan of geriatric worms, flies and mice, and indoles may represent a class of therapeutics that improve the way we age, but not how long we live. The essential amino acid tryptophan, which is the least abundant in terms of its use in proteins, is provided by the diet or produced by gut bacteria, can cross the blood-brain barrier under the influence of the gut microbiota and is a biosynthetic precursor for a large number of complex microbial natural products. Recent in vitro studies have indicated the decreased production, transport, and catabolism of tryptophan in patients with a number of disorders.
Researchers have postulated that a chronological age threshold at which the composition of the microbiota suddenly changes does not exist, and changes occur gradually with time. However, compared with previous investigations, our study suggests a threshold or age at which the microbiota-based metabolism of tryptophan and indole begin to be significantly reduced, which may have health-related consequences on ageing if not treated accordingly. Indeed, based on our results, from the age of 11 years, the human gut microbiota may exhibit a decreased capacity to produce these metabolites, and from the age of 34 years, this capacity may be reduced by more than 90% compared to childhood. The results of this study reinforce the hypothesis that dietary supplementation with indole and tryptophan exert a beneficial effect on elderly individuals because their gut bacteria exhibit an impaired capacity to produce these molecules required for extending the healthspan. This supplement can be administered beginning at the age of 11 years, at which time a 50% decrease in the production of these metabolites occurs, and particularly beginning at the age of 34 years, when a greater than 90% reduction occurs