Combinatorial data sets, including information from the microbiome, are opening up new avenues in preventative medicine
“I think the microbiome in many ways is the one answer to the problems of preventative medicine,” says Raja Dhir. Playing host to bacteria, it offers quantifiable risk factors and assessments of our organ systems, and currently has predictive power for conditions like major depressive disorder and colon cancer. “Before we were looking at one data set, maybe you’d look at a biomarker, you’d look at one organ system; but now we’re actually building quite rich combinatorial data sets,” he says. This data from the microbiome combined with metabolomics can lead to earlier disease intervention, and has the potential to predict responders versus non-responders to current drug treatments.
The path of the microbiome begins at birth
In a healthy microbiome, “we trade shelter to this community of bacteria, yeast, fungi, viruses as well, in exchange for what we believe is a symbiotic relationship,” says Dhir. “In a perfectly healthy state, they help us digest our food and make nutrients, and we give them a place to reproduce.”
Within the first 30 days of life, we are exposed to many microbes from our mothers. A few big drivers of the early microbiome include mode of delivery (vaginal or cesarean), breastfeeding, and antibiotic use by the mother or baby. Around the age of two, our microbiomes hit a steady state, progressively building throughout childhood. “Puberty is when you hit your most mature, steady-state version and then you experience a progressive decline of diversity as you age,” explains Dhir.
Assessing the health of your microbiome is simple: the presence or absence of abdominal pain, gas, bloating, discomfort, intestinal transit time, and the quality of daily bowel movements are all factors.
We should be eating a broad diet
“Non-easily digestible carbohydrates is probably the best single food,” says Dhir of how we should be eating, “starting from the minute that solid foods are tolerated all the way through to the end of life.”
“Non-easily digestible carbohydrates is probably the best single food, starting from the minute that solid foods are tolerated all the way through to the end of life.”
“I recommend you go broad and I recommend you go diverse,” he says. No one food should be prioritized. He offers the example of a fermented tea like kombucha: In the fermentation process, the tea creates secondary and tertiary metabolites, which you then drink. “No one’s actually designed the study to know what your own microbiome would make of those metabolites if you just drank the tea before the fermentation,” he explains. If you were to drink the tea before fermentation, “your own microbiome would want to degrade all those same base oligosaccharides from the cabbage, as well. Don’t deny it the opportunity to do that.”
There are specific definitions behind all the marketing for prebiotics, postbiotics, and probiotics
The definitions between these three types of products is heavily marketed. Probiotics are live organisms. “That’s unequivocal,” says Dhir.
“Prebiotics are our substrates,” Dhir explains — it’s the food for the bacteria in your gut. “My general thinking on prebiotics is that if you eat a diverse, rich diet you do not need prebiotics. You get plenty.”
He does find some polyphenol-based prebiotics interesting, as it’s challenging to consume high amounts of polyphenols without excessive intake of certain foods or beverages (for example, 100 raspberries, 10 pomegranates, or 15 cups of green tea per day). “That’s really what it would take from a consumption standpoint to start to modulate the microbiome or to start to produce really high levels of metabolites of interest,” Dhir says.
“Postbiotics is the newest buzzword,” he says of these supplements for what’s left behind after your body digests the pre- and probiotics. But Dhir is concerned about the dosage. “No one’s done really good dose escalation studies on postbiotics – at least as a supplement – for me to be saying you should take this right now.”
Centenarians have microbiomes similar to an infant’s
The microbiome’s role in longevity is not about it becoming richer with age. Rather, the microbiome either remains stable to provide protection, or it deteriorates, leading to various health conditions. For example, cardio metabolic outcomes are highly correlative to the microbiome (a paper that’s currently under review with Nature Family Journal is looking at which other organ systems the microbiome correlates to).
“Typically, people who age well have gut microbiomes that resemble much younger gut microbiomes,” Dhir explains. Centenarians, for example, have an abundance of Bifidobacterium, a bacteria most commonly found in infants and probiotics. While studies are looking at these centenarians, we don’t have early-life data for them. The first good cohorts where we can establish early life microbiomes are from 2013, but other studies are looking at people ages 40 to 70, which is when we can start to see transitions in the microbiome, especially with sex-specific differences around menopause.
In terms of what’s next for preserving the microbiome for long-term health, Dhir expects that we will focus more on the relationship between diet and the microbiome. “Personalized diets in combination with more exotic probiotics might be a very interesting evolution of fermented foods – maybe single-strain probiotic products,” he says. “I think that if you continue along that path, you start to find diet-microbe pairs, which are just wildly optimal.”
