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In this episode of Longevity by Design, our hosts, Dr. Gil Blander and Ashley Reaver, MS, RD, CSSD, are joined by Dr. Filipe Cabreiro. An expert in the gut microbiome and principal investigator at The Cabreiro Lab, Dr. Cabreiro discusses the latest science on the connection between gut microbial and healthy aging. Join us to learn how to improve microbial diversity and assess gaps in the knowledge that are currently under investigation.
Meet Longevity by Design’s podcast guest, Dr. Filipe Gomes Cabreiro
Dr. Filipe Cabreiro is the principal investigator at The Cabreiro lab, is a professor at the University of Cologne in Germany, and is an associate professor at Imperial College London. Dr. Cabreiro earned his PhD in Biochemistry, and his main research interests include the molecular mechanisms underlying metabolic disease, cancer, and aging. The Cabreiro lab closely studies the gut microbiome, including the effects of diet, lifestyle, and metformin on microbial health.
What is the gut microbiome?
To begin the episode, Dr. Cabreiro briefly overviews the gut microbiome. He explains that the gut is essentially an ecosystem living within us that dictates our physiology. “We carry an enormous variety of microbes that produce molecules which influence our behavior, our ability to obtain nutrients, our production of vitamins, and even our communication with the immune system. Microbe diversity trains our immune system to be more aware of other pathogens,” he states. Research on the gut microbiome has expanded in recent years, and Dr. Cabreiro explains just how important it is for improving healthspan.
How the gut microbiome links to healthspan
So what is the link between the gut microbiome and healthspan? Dr. Cabreiro emphasizes that microbiome health is highly correlated with the aging process. To further explain, he discusses three possible points of intervention within the microbiome.
- First, Dr. Cabreiro shares exciting new research that showed the success of a modified microbe that has been created and can be implanted in humans. This microbe can then act as a delivery system allowing the body to produce desirable molecules, leading to favorable health outcomes.
- A second possibility of intervention is to detect species that are detrimental to aging and create targeted therapies to eliminate those microbes. Elimination of undesirable microbes can encourage healthy aging.
- Third, if a specific microbe is already naturally producing something positive, treatment can be purpose-designed to enhance its abundance. “This could be a dietary intervention, or it could be pharmacological in a way that could really enhance and increase the abundance of this microbe and, therefore, push towards that positive effect,” says Dr. Cabreiro.
Dr. Cabreiro also gives his insight into microbiome clocks which have recently gained popularity as a means to predict aging. He agrees that these clocks very clearly map our aging process and can predict human aging within five to six years of error. “We can show very clearly that by changing the composition of different microbes, or even within a microbe, to produce a desired molecule, we can very strongly influence the aging process,” he explains.
Host-microbe-metformin-nutrient interactions
Shifting to the role of nutrition on microbial health, Dr. Cabreiro discusses his lab’s published research that showed how diet could modulate aging in a model organism. His team developed a screening method to challenge microbes with 400 different nutrients. “We really went to the molecular level of nutrition and tried to understand which nutrients could alter metabolism in the context of the compound metformin. We showed that indeed metformin and nutrition could influence and act together, and the microbes can understand this interaction,” explains Dr. Cabreiro. The team mapped the impact of different nutrients on the microbes. They could determine which pathways were being activated and the consequence of that activation. Manipulation on this level could lead to the production of molecules that have a pro-longevity effect.
The importance of dietary diversity
When asked for his advice on optimizing the gut microbiome through dietary interventions, Dr. Cabreiro recommends a varied diet. He observes that the literature agrees that food and nutrient diversity benefits health. "The richer a microbiome is in diversity, the more resilient it is and the more capable it is of withstanding invasion from infections," he says. Dr. Cabreiro explains that diversity also increases the microbiome's ability to communicate amongst itself. "Microbes within our gut work like factories—one produces something and sends this product to another microbe. We are at the receiving end of this communication where we'll get some of those molecules, so as rich a diet as possible is beneficial," he says.
In addition to positively impacting the gut microbiome with nutrition, there are ways in which our diet has negative effects on microbial composition. For example, while diets high in fat and sugar are known to be detrimental to health in many ways, Dr. Cabreiro says extensive research shows that much of this negative consequence is created by a dysbiotic microbiome. "High sugar, high fat shift our equilibrium, leading to the production of lipopolysaccharides because there's an enrichment in certain types of bacteria that produce those molecules, which can cause inflammation—one of the known drivers of aging," he says.
Lifestyle factors that impact the gut microbiome
Following the discussion on how our nutrition modulates the microbiome, Dr. Cabreiro discusses other lifestyle factors that can impact our gut health.
First is sleep – he says it is well established that our circadian rhythm impacts our microbiome. Individuals with disrupted sleep patterns will also have a completely unbalanced microbiome, and researchers are trying to disentangle this relationship to determine if this relationship is causal or consequential. "With sleep deprivation or sleep dysfunction, often you end up taking medicine for it, which is likely to impact the microbiome. If you don't take medication, you are likely to engage in certain behaviors like eating at different times during the night, which, again, will alter the natural rhythm of your microbiome too," explains Dr. Cabreiro. While it is unclear if just sleep deprivation is enough to change the microbiome, the behavior changes that come with sleep deprivation certainly impact microbial homeostasis.
The next question of interest was probiotics and whether or not they improve our gut flora. Dr. Cabreiro clarifies that the research is not conclusive yet. "If you have 1 billion people taking probiotics, just by random chance, you will potentially have the right combination that can make it work. It's more by chance than by design," he says.
Advice on living a healthier longer life
To close the episode, Dr. Cabreiro shares his top tip for improving healthspan. He advises minimizing highly processed foods, explaining that diet may be the most important contributor to our health. “My best advice would be to stay away from processed foods. They negatively impact host cells directly and also detriment the body indirectly through the microbiome.”
