In 1895, on his 50th birthday, Elie Metchnikoff became increasingly anxious about aging.
As a result, the Nobel Prize-winning Russian scientist and one of the founders of immunology shifted his attention from immunology to gerontology—a term he coined.
He was fascinated by the role that intestinal bacteria play in health and disease—and suggested that people in parts of Eastern Europe lived longer because they consumed various fermented foods containing lactic acid bacteria.
Though popular at the time, this theory linking gut microbes to healthy aging was largely ignored by scientists until relatively recently.
We now recognize the importance that trillions of bacteria, known as the gut microbiome or microbiota, play in regulating health and disease.
For nearly a decade, evidence has been accumulating that the composition of the microbiome changes with age.
In 2012, research conducted by my colleagues at University College Cork in Ireland showed that diversity in the microbiome was related to health issues in old age, including frailty.
But we still didn’t know much about the microbiome’s effect on brain aging.
In 2017, we revisited Metchnikoff’s ideas, placing them in the context of brain aging, and showed that aging induced changes in the microbiota and the immune system, and this was associated with cognitive decline and anxiety.
However, this study, like many others in the field, showed only one association between aging and these factors. It didn’t prove that one thing caused the other.
In a subsequent study, we took it a step further by showing that a microbiota-enriched diet with prebiotic inulin (a prebiotic that feeds beneficial bacteria in the gut) was able to lessen the effects of aging on the brains of middle-aged mice.
However, it was not yet clear whether the microbiota itself caused the brain’s aging to slow down.
In our latest study, we showed that by taking the microbiome from young mice and transplanting it into old mice, many of the effects of aging on learning and memory and immune deficiencies can be reversed.
Using a maze, we showed that transplanting fecal microbiota from young to old mice caused older rodents to find a hidden platform faster.
the immunological connection
Aging is associated with increased inflammation in all body systems, including the brain.
It is clear that immune processes play an important role in the aging of the brain, with increasing emphasis on the role of a specific immune cell, the microglia.
Ironically, it is the same type of cell that Metchnikoff visualized under the microscope, albeit in other tissues, in the late 19th century.
We now also know that the activation of these cells is under constant regulation by the intestinal microbiome.
So the next part of the puzzle was to see if the negative effects of aging on immunity were also reversible by transplanting the microbiota from young mice to old ones. And, in fact, much of the inflammation has gone down.
Finally, we showed that chemicals in a brain region involved in learning and memory (the hippocampus) were more similar to those in young mice after microbiota transplantation.
Our results conclusively show that the microbiome is important for a healthy brain in old age.
Was Metchnikoff’s departure from immunology premature in understanding the secrets of aging?
In fact, the relative contribution of immunological changes observed in mice that received young microbiota to the overall rejuvenating effects deserves further study.
But two important questions remain. What are the exact mechanisms at play? And we can translate these remarkable discoveries
rats are not human
Working with a controlled situation, as in the case of mice — which have well-defined genetics, diet and microbiome — is very different from looking at humans. We must be careful not to misinterpret these findings.
We are not advocating fecal transplants for people who want to rejuvenate their brains.
Instead, these studies point to a future where there will be a focus on microbiota-targeted diets or bacteria-based treatments that will promote optimal gut health and immunity to keep the brain young and healthy. These strategies will, in fact, be a more palatable elixir.
Metchnikoff’s general principles seem to be correct: protecting intestinal microbes may be the secret of the fountain of youth. With advances in healthcare, longevity has increased significantly.
And while we can’t stop the passage of time, we can develop treatments that will protect our brains from deterioration—and we have more than a hunch that the microbiome might be one of the ways.
However, much work is still needed to better understand how gut microbes are able to “rewind” some features of an aging brain.
*John Cryan is Vice President of Research and Innovation at University College Cork, Ireland.
This article was originally published on the academic news site The Conversation and republished here under a Creative Commons license. Read the original version here (in English).