11/04

by Buck Institute

The Microbiome: you and your trillion little friends

By Eric Verdin, President and CEO of the Buck Institute

The microbiome is rightfully having a scientific moment (more like a scientific decade) and it seems like the right time to think about its role in aging. The microbiome - the hundreds of species of bacteria living on and within us, and especially in our gut, - has emerged as an integral regulator of overall health. Indeed, there is a tight correlation between changes in the microbiome and aging as well as with disease.

The microbiome is full of commensal bacteria, bacteria that have a mutually beneficial relationship with us. In exchange for giving them a cozy place to live and a consistent all-you-can-eat buffet, they break down nutrients from our food that we can’t access. They also can transform some of the food we eat in unique signals that communicate with the rest of the body. The relatively recent discovery that our gut can communicate directly with the nervous system has led to a flurry of investigations into the “gut-brain axis”.

At the most basic level, the microbiome helps us benefit from nutrients in our food. The human digestive system cannot process all the types of fiber contained in our diet. When undigested fiber arrives in our colon, the bacteria feast on it, producing short chain fatty acids that can be used as fuel by our own cells to maintain a healthy gut lining.  Bacteria living in our gut can also synthesize vitamins K and B.

Other discoveries about the microbiome have been more startling. For example, researchers in 2015 uncovered a role for the microbiome in regulating our circadian clock, the internal clock that regulates many biological functions by turning genes on and off in an approximately 24 hour rhythm. Germ-free mice without a microbiome do not regulate their genes in the same pattern as typical lab mice; a high fat diet also seems to disrupt this important biological regulator by altering the microbiotic population in the mice. There is further emerging evidence that the microbiome influences immune activity and even neural activity. Not only does gut dysbiosis, an abnormal gut flora, seem correlated to some Parkinson’s diagnoses, there are some individuals who don’t respond to the Parkinson’s drug Levodopa because their gut bacteria digest it before their brains can get it.

With an understanding of the many important functions of our gut microbiome, despite the acknowledgment that there are likely many functions that we don’t yet know about, it seems clear that there is a role for our microbiome in the biological aging process. Some of the most direct evidence for this is from a 2017 study by Dario Valenzano. A Nature report on the study (amazingly titled ‘Young Poo’ makes aged fish live longer) described that replacing the microbiome of older fish with that from younger fish resulting in a median lifespan extension of 37% relative to control. This is a stunning result, but it remains unknown exactly how the microbiome regulates lifespan. As a scientist, it is exciting that there is still so much to learn. Of course, this means that we still have more questions than answers.

Over the course of a lifetime, an individual’s bacterial population seems to shift from one that is more beneficial to one that is more pathogenic. The dynamics within the populations are extremely complex in part because bacteria divide very quickly and live for thousands of generations over our one lifetime. This means that while we are going about our daily life, there is an ecological battle raging within us. Bacteria are competing with each other, responding to changing environmental conditions, and accumulating adaptive mutations that can help them survive better than their rivals. For some reason, perhaps because of a declining immune system with age, the more pathogenic bacteria gain the upper hand over time.

Buck adjunct faculty Dr. Alex Zhavoronkov’s work sampling the gut microbiome of over 1000 people between the ages of 20 and 90 got a great write-up in Science Magazine. He found that changes in the species composition with age are predictable enough that he could develop an algorithm to predict age based on microbiome data. This is an exciting prospect because it could allow us to use microbiome data to assess how a person is aging, and whether there are changes they could make to create a better balance in their gut bacteria.

Maintaining or increasing microbe diversity is one way to help your microbiome continue to do its job over time. Perhaps not surprisingly, diet is the best way we know of to do this. There are two ways to do this: by directly ingesting the beneficial bacteria (probiotics), or providing nutrients that support a healthy mirobiome (prebiotics). Increasing dietary fiber to provide good fuel for good bacteria is one important change you can make. Studies show that people who eat more fiber are able to increase the number of Bacteroidetes (one type of beneficial bacteria) in their system in just a few weeks. Another way is to get more sleep. A very recent study found an association between less sleep and lower microbiome diversity. Of course, this is just an association. Perhaps those with more diverse microbiomes are able to sleep better (perhaps because of their role in regulating our circadian clocks!). In reality, it is probably a mixture of both as good sleep is good for your microbiome and a healthy microbiome is good for sleep.

A popular method to support microbiome health is to consume probiotics, directly consuming the bacteria that are thought to be good for health. This includes probiotic supplements as well as fermented foods like yogurt, pickled vegetables, and kombucha (fermented tea). These foods are delicious and generally very healthy. There is pretty good evidence that they are good for digestive health, but there is not yet strong clinical evidence that they are beneficial for more complex conditions like diabetes or cancer. As with my recent post on vitamins, it is important to note that not all probiotic supplements contain what is reported on their labels, and bioavailability can be an issue. Regarding kombucha specifically, the bacteria these drinks contain haven’t been proven to be healthy, so experts say you shouldn’t drink it unless you like it.

I always feel quite dry and repetitive when I reach the summary portion of these blog posts, but I also think it’s critical to highlight how cutting edge this science is, and how much we still have to learn. From a holistic perspective, a healthy, diverse diet and yes, even exercise are good for your little friends living inside you, but there are not yet clinical recommendations of specific bacterial populations that support healthy aging or prevent disease. I look forward to the day that we can use our understanding of the microbiome to stay ahead of chronic disease. Until then, continue to stay up to date with the Buck to keep abreast of updates in this exciting field!

Science is showing that while chronological aging is inevitable, biological aging is malleable. There's a part of it that you can fight, and we are getting closer and closer to winning that fight.

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