Every Microbiome Tells a Changeable, Computable Story

By Deborah Borfitz 

People are not only human but also microbial, a summation largely of the choices they make: their social interactions, the food they eat, medications they take, their activity level, and daily habits. The microbes that are transmissible person-to-person are sometimes beneficial, but the odds are slightly better that they are causing harm, according to computational biologist Nicola Segata, Ph.D., professor and principal investigator at the CIBIO department of the University of Trento and principal investigator at the university’s European Institute of Oncology in Milan. 

The microbial part of the human body (roughly 39 trillion cells) gets built over a lifetime and is “what we can change the most to impact our health trajectory,” says Segata. Better understanding these microbes and their role in health and disease is key to supporting healthy-aging efforts as well as medical practices such as fecal microbiota transplantation (FMT). 

As Segata and his colleagues recently found, cohabiting people share more oral and gut microbes with each other than with other people in their communities (Cell Press Blue, DOI: 10.1016/j.cpblue.2026.100034). The researchers also found a link between more transmissible microbes and some risks for some diseases, which could help design more targeted therapies for improving people’s microbiomes. 

When estimating the transmissibility of different microbes, they found that among the most transmissible bacteria in the gut were associated with biomarkers of type 2 diabetes and poor cardiometabolic health and in the oral microbiome were, most notably, two microbes associated with colorectal cancer and several opportunistic pathogens. The difficult task ahead is figuring out how to predictably change that internal ecosystem. 

It’s not as if people can be categorized by microbiome type and prescribed the “same recipe” to improve their health status, says Segata. “Everyone has a unique microbiome … way more unique than our human genome.” 

Recurring Bacteria 

As has been covered in previous papers, “microbes are very rarely coming directly from the environment or food,” says Segata. “In 99% of cases, they are coming from other people because gut microbes are very well adapted to living in the gut of humans.” 

Individuals without any social and physical interaction share about 15% of strains after living together for two to three years, he says. Even in the first day of life, 50% of the microbes found in the gut of babies comes from the mother, provided the baby wasn’t delivered by C-section. The research team recently reported that 1-year-old babies in daycare share an average of between 20% and 30% of their microbiome with other babies in the same room after only four months (Nature, DOI: 10.1038/s41586-025-09983-z).   

Pro-inflammatory microbes, while found to be more transmissible, have differing and largely unexplored effects in terms of the relative risk of people developing microbiome-associated diseases. Part of the problem is that bacteria can be “favoring” a disease rather than directly causing it, explains Segata. That is, microbes that typically live harmlessly in the body instead facilitate inflammation and chronic disease when the microbiome is unbalanced. 

The recurring bacteria that are higher in people with diabetes and those transitioning to diabetes could be there for many plausible reasons, including a diet that acts directly on insulin resistance, he says. “It is difficult to disentangle what is the effect of each single bug on the increased risk of disease … our body is a very complicated system.” 

Asking whether those recurring bacteria are more, or less, abundant in healthy people is a relevant question, says Segata. But the association is not proof that the microbes are causing diabetes.  

With colorectal cancer, the added difficulty is that several of the microbes found only in the stool of people affected by the disease are abundantly found in the oral cavity of all people, healthy or not, Segata says. These specific bacteria are colonizing the growing tumor microenvironment in the gut, which is a mechanism separate from oral-to-gut transmission itself. 

Computational Feat 

Segata’s specialty is metagenomics, the sequencing of the DNA of microbial communities that generates a huge amount of data requiring advanced computational tools to interpret. A “computational microscope” is required when it comes to studying transmissibility where the task is to distinguish or match pairs of strains and their genomes to learn whether they were transmitted directly between individuals or possibly acquired independently from a shared environment. 

“If we find exactly the same strain, the most plausible hypothesis is that they were transmitted,” he says. Arriving at that conclusion means solving a lot of puzzles—i.e., the reconstructions of the genomes of each single strain in the microbiome—together. 

For the latest Cell Press Blue study, he and his team analyzed metagenomic data from the oral and gut microbiomes of 430 people living in 207 households in Italy and from a previous study from Fiji. Identified microbial strains within individuals were then compared to strains between people who lived together to see whether transmission was occurring.  

This led to the discovery that cohabitants shared significantly more oral and gut strains than people from the same population who did not live together. On average, cohabiting individuals shared 19% of their gut microbiome strains and 26% of their oral microbiome strains, compared to 6% and 0%, respectively, for individuals living in different households. Romantic partners shared an average of 44% of their oral microbes with each other, the logical explanation being that they kiss. 

Lifelong Story 

Segata says experiences with his own children helped drive his interest in microbiome-related research. Studies on mother-to-infant microbial transmission started around the time his oldest, now 12 years old, was born. “It is not only the mother but also the father … who transmits certain strains to the baby.” 

And vice versa, from the everyday contact required of parenthood, he adds. The idea for the latest Nature study arose after he spent a semester chronically sick from the constant barrage of infections brought home from a daycare center.  

But with the bad comes some good. In a separate paper published in Nature late last year, Segata and his team analyzed more than 34,000 microbiomes to identify 50 gut bacteria strongly linked to better health (DOI: 10.1038/s41586-025-09854-7). They also discovered two dietary interventions that increased the abundance and prevalence of the favorable species while reducing that of the unfavorable ones. 

One of the somewhat provocative take-home messages is that having a healthy diet and lifestyle “not only helps you but also the people around you,” says Segata. The joke is that microbiome testing might be used to prove compatibility of cohabiting couples, but that’s a marketing gimmick and not hard science. 

But at the population level, it’s more of a legitimate field of inquiry, Segata continues. His earlier work identified a “completely different” gut microbiome in westernized and non-westernized populations, the latter of which mirrors the microbes found in ancient mummies between 5,000 and 6,000 years old. 

“The story here is that if a whole population eats fast food every day for every meal and forgets about eating fiber, those microbes eating and living and growing on fiber will disappear from the population,” says Segata. “And if they are gone from the population, even if you are the healthiest individual in the world, you don’t have sources for these bacteria to colonize your gut … [and] it is then extremely difficult to get them back.” 

Clinical Implications 

A good first step, at the population level, would be to cultivate, store, and maintain beneficial gut bacteria that are dropping in numbers in Western populations, says Segata. There is also a lot of interest in both the wellness and medical fields about how to alter the microbiome in a simple and reproducible way with, for example, next-generation probiotics and prebiotics as well as FMT—”the most extreme way of using transmission in a medical setting.” 

There is no dispute that it is “a gross procedure, but it works,” Segata says, at least for treating recurrent Clostridioides difficile infections in immunocompromised people. FMT has dramatically transformed C. diff from a frequently deadly, chronically relapsing condition into a highly curable one, and it is likely to be clinical practice soon for several other diseases. 

To make FMT “less gross,” efforts are underway to cultivate individual microbes in isolation and then assemble them to simulate commensal microbial communities, he adds. But the therapy lacks the standardized, predictable, and universally applicable success rates required for widespread adoption as a treatment for many diseases. 

“It is a matter of defining the tradeoff between benefits and potential problems, because there may be diseases that are only 10% associated with the microbiome,” says Segata. The question is whether for conditions beyond C. diff the benefits are worth the risks given the lack of long-term safety data and the potential for severe adverse reactions if patients are not medically supervised.