Fight Aging!

Evidence suggests that the gut microbiome is influential on long-term health and late life mortality, to perhaps a similar degree as exercise. The various populations of microbial life found in the gut change with age; microbes producing beneficial metabolites are lost, while microbes that provoke chronic inflammation or other issues increase in number. Experiments in short-lived species have shown that transplanting a youthful microbiome into an older individual results in improved health and extended life span. In principle, similar effects could be achieved by some sort of intensive oral probiotic treatment, but that has not yet been demonstrated in animal studies. Researchers have also shown that guiding the immune system to more aggressively attack problem gut microbes can improve the microbiome and its influence on health.

In today's open access paper, researchers propose that regional differences in diet mean that there is unlikely to be one optimal gut microbiome to promote longevity. This seems a reasonable prediction, given the degree to which human diet does vary around the world, and the way in which diet interacts with the gut microbiome. It still seems likely that there are universally beneficial changes that one can make to any aged microbiome, in humans or other species, such as enabling the immune system to better remove problem microbes. Early approaches to therapies are likely to involve such universal, narrow improvements; personalized medicine is more challenging problem.

Regional Diets Targeting Gut Microbial Dynamics to Support Prolonged Healthspan

Centenarians, who have escaped or survived lethal diseases earlier in life, may be considered a spontaneous model of healthy ageing. The gut microbial composition of centenarians has consistently been reported to differ in phylogenetic composition from that of younger people. Interestingly, within centenarian populations, species have been reported to display regional characteristics, further supporting that environmental and/or lifestyle factors including the diet, shape microbial composition.

For example, in an Italian cohort, the centenarian microbiome was found to be dominated by the same two microbial families as in the other age groups (<75 years old) of the population, namely Veillonellaceae and Ruminococcaceae (Firmicutes phylum), but was specifically enriched in the genera Akkermansia, Bifidobacterium, and Christensenella. In contrast, the Chinese Hainan Centenarian Cohort was dominated by Bacteroides (Bacteroidetes phylum) and Escherichia (Proteobacteria phylum). Long-term elderly care residents in the Irish ELDERMET Cohort also had a gut microbiome dominated by Bacteroidetes. Importantly, although the aggregate faecal microbiome in ELDERMET was dominated by Bacteroidetes, the residents showed extraordinary inter-individual variation with 3-92% Bacteroidetes and 7-94% Firmicutes, hinting at a long-term effect of their dietary habits.

The results of the Italian study are also in contrast to those of another Chinese Centenarian Cohort from the Guangxi region, who harboured significantly higher abundance of the genera Escherichia and Roseburia, and reduced abundance of Akkermansia, Lactobacillus, Faecalibacterium, Parabacteroides, Butyricimonas, Coprococcus, Megamonas, Mitsuokella, and Sutterella. A Korean centenarian study found trends similar to both Italian and Guangxi Chinese centenarians, with higher abundance of Akkermansia and Christensenella, and Escherichia, respectively. They also displayed increased abundance of Clostridium and Collinsella, and reduced abundance of Faecalibacterium and Prevotella compared to the general population.

At present, we do not have a good understanding to explain these geographical variations in the centenarian gut microbial composition or to unequivocally answer if there are certain microbial species globally associated with longevity. In the reviewed studies, some microbial genera associated with healthy elderly populations include Roseburia, Escherichia, Akkermansia, Christensenella, Bifidobacterium, and Clostridium, but they are all highly variable across populations. Based on these cross-sectional observations, it seems unlikely that a universal pro-longevity gut microbiome exists. Rather, the optimal microbiome for healthspan appears to be conditional on the microbial functionality acting on regional- and ethnicity-specific trends driven by cultural food context.