The Human Microbiome and Aging: What’s the Latest Research?

The human microbiota consists of trillions of microbial cells, including bacteria, fungi, viruses, bacteriophage and protozoa. The term “microbiota” refers to these organisms, while the “human microbiome” denotes the genomic content of the organisms (microbiota) that inhabit the body. The microbiome's influence on human health and disease is well documented with these organisms playing a role in enhancing or impairing metabolic and immune functions. Recent findings have identified that the microbiome may also play an important role in aging.

The complex process of aging is characterized by accumulating damages linked to biological mechanisms referred to as the “hallmarks of aging”. These processes contribute to an increased vulnerability to age-related diseases such as Alzheimer's.

Studies have shown that aging can change a person’s microbiome, particularly within the gut. By making conscious changes to diet, it may be possible to influence the microbiome in ways that mitigate age-related diseases. Here, we highlight some of the latest findings on the link between the microbiome and aging.

The skin microbiome and the development of wrinkles

A recent study published in Frontiers in Aging found a positive association between the diversity of the skin microbiome and lateral cantonal lines (crow’s feet wrinkles), generally viewed as a key sign of skin aging. They also observed a negative correlation between microbiome diversity and transepidermal water loss. Further analysis of the data enabled them to identify several microorganisms of interest for further research.¹

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The Skin Microbiome

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The study involved the analysis of data collected from 13 previous studies by L’Oréal, consisting of 16S rRNA amplicon sequence data and corresponding skin clinical data for over 650 female participants, aged 18‒70 years. The multi-study analysis compiled the data to identify trends related to specific microbes while accounting for other variables, such as age.

"By confirming a link between the microbiome and skin health, we've laid the groundwork for further studies that discover specific microbiome biomarkers related to skin aging, and, one day, show how to modify them to generate novel and highly targeted recommendations for skin health," said co-author Rob Knight, founding director of the Center for Microbiome Innovation and professor of pediatrics, bioengineering, computer science & engineering and data science at UC San Diego.

A unique shift: how the gut microbiome develops and diversifies with age

Researchers from the Institute of Systems Biology and their collaborators identified distinct signatures in the gut microbiome associated with healthy and unhealthy aging trajectories. Published in Nature Metabolism, the study revealed that as individuals age, their gut microbiome becomes increasingly unique. This corresponded with a steady decline in the abundance of core bacterial genera that tend to be shared across humans, primarily Bacteroides.²

The authors concluded, “retaining a high Bacteroides dominance into older age, or having a low gut microbiome uniqueness measure, predicts decreased survival in a 4-year follow-up. Our analysis identifies increasing compositional uniqueness of the gut microbiome as a component of healthy aging, which is characterized by distinct microbial metabolic outputs in the blood.”

Investigators from Cedars-Sinai have also identified that some types of bacteria in the small bowel increase with age. The findings were published in Cell Reports. In this study, investigators analyzed samples from the small intestine and identified specific microbes that appear to be influenced solely by a person’s chronological age. ³

“Coliforms are normal residents of the intestine. We found that when these rod-shaped microbes become too abundant in the small bowel ‒ as they do as we get older ‒ they exert a negative influence on the rest of the microbial population. They are like weeds in a garden,” said study co-author Dr. Gabriela Leite, lead project scientist at Cedars Sinai’s Medically Associated Science and Technology (MAST) program.

Investigators also found that as people age, the bacteria in the small intestine shift from those that prefer oxygen to those that survive in an environment with lower oxygen. The scientists hope to further understand this change and its implications as the research continues.

HIV, gut permeability and premature aging

A study, published in the journal Microbiome in February 2024, has identified a connection between the microbiome, viral damage to the gut and premature biological aging. Researchers analyzed samples from the colon, ileum, stool and blood of people living with chronic HIV infection and noted that the damage associated with the infection led to increased gut permeability and premature aging of both systemic and intestinal tissues in these individuals.⁴ They were also able to identify the specific microbial compositions and microbiota-related metabolic pathways related to intestinal permeability and biological aging.

Notably, they observed a connection between accelerated biological aging and the microbiomes of both the colon and ileum, but not the fecal microbiome. This suggests that the location of the microbiome impacts its effects and highlights the importance of sampling intestinal tissues to truly understand the connection between the microbiome and age.

These findings open new avenues for developing strategies to combat these bacteria and their byproducts, potentially extending the duration of good health of individuals living with chronic conditions such as HIV.

How can diet affect the human microbiome and aging?

With the establishment of a link between the microbiome and aging, researchers are now looking at ways to manipulate the microbiome to improve healthy aging trajectories. One study, by researchers at the University of Exeter, found that drinking beetroot juice can positively alter the oral microbiome. Their research is published in Redox Biology.⁵

Oral bacteria play a key role in turning nitrates found in foods such as beetroot into nitric acid. This helps to regulate blood vessels and neurotransmission. Older people have been found to have lower nitric oxide production which is associated with poorer vascular and cognitive health.

In the study, 26 healthy individuals aged 70‒80 years, took part in two ten-day supplementation periods. One period with a nitrate-rich beetroot juice and another with a nitrate-free placebo, which they drank twice daily.

The results showed that taking the nitrate-rich beetroot juice supplement resulted in higher levels of bacteria associated with good vascular and cognitive health, and lower levels of bacteria linked to disease and inflammation.

"Our findings suggest that adding nitrate-rich foods to the diet – in this case via beetroot juice – for just ten days can substantially alter the oral microbiome (mix of bacteria) for the better,” said lead author Anni Vanhatalo, professor of human physiology/associate pro-vice-chancellor research and impact at the University of Exeter.

"Maintaining this healthy oral microbiome in the long term might slow down the negative vascular and cognitive changes associated with aging," said Vanhatalo.

Another study has shown that a calorie-reduced diet can help delay the development of metabolic diseases. Researchers identified that these changes are mediated by an altered gut microbiome which in turn can slow down the deterioration of the immune system in old age. The findings were published in Microbiome.⁶

The team analyzed how a very low-calorie diet (800 kcal/day for 8 weeks) affected the gut microbiome of an obese woman (a body mass index (BMI) of at least 27 kg/m²). The researchers created a gnotobiotic mouse model by transplanting the gut microbiota of the woman before and after dietary intervention into germ-free mice.

After transplanting the diet-altered microbiota, glucose metabolism improved, and fat deposition decreased. In addition, the level of specific memory T and B cells was also reduced indicating delayed immune aging.

“These findings suggest that the benefits of a low-calorie diet on metabolism and the immune system are mediated via the gut microbiome,” said the study’s first author, Julia Sbierski-Kind, group leader and physician scientist at the Institute for Diabetes Research and Metabolic Diseases. However, the researchers emphasize that the findings are based on a single test subject only so the experiment will need to be repeated to confirm these results.

Conclusion

References

1.      Myers T, Bouslimani A, Huang S, et al. A multi-study analysis enables identification of potential microbial features associated with skin aging signs. Front in Aging. 2024;4. doi: 10.3389/fragi.2023.1304705

2.      Wilmanski T, Diener C, Rappaport N, et al. Gut microbiome pattern reflects healthy ageing and predicts survival in humans. Nat Metab. Published online 2021. doi: 10.1038/s42255-021-00348-0

3.      Leite G, Pimentel M, Barlow GM, et al. Age and the aging process significantly alter the small bowel microbiome. Cell Rep. 2021;36(13). doi: 10.1016/j.celrep.2021.109765

4.      Singh S, Giron LB, Shaikh MW, et al. Distinct intestinal microbial signatures linked to accelerated systemic and intestinal biological aging. Microbiome. 2024;12(1):31. doi: 10.1186/s40168-024-01758-4

5.      Vanhatalo A, L’Heureux JE, Kelly J, et al. Network analysis of nitrate-sensitive oral microbiome reveals interactions with cognitive function and cardiovascular health across dietary interventions. Redox Biol. 2021;41:101933. doi: 10.1016/j.redox.2021.101933

6.      Sbierski-Kind J, Grenkowitz S, Schlickeiser S, et al. Effects of caloric restriction on the gut microbiome are linked with immune senescence. Microbiome. 2022;10(1):57. doi: 10.1186/s40168-022-01249-4