The top 50 gut bacteria: how a landmark study finally scored the microbiome
A large study of more than 34,000 people ranked 661 gut species and identified a top 50 linked to healthier diets and cardiometabolic markers, plus a bottom 50 linked to the opposite. Two randomised trials then showed that changing what you eat moves those bugs in the desired direction within 12 to 18 weeks. Many of the best bacteria are so new they have never been grown in a lab.
Overview
Jonathan Wolf sits down with Professor Nicola Segata and Professor Sarah Berry to unpack what they describe as the biggest breakthrough in microbiome science in a decade. Drawing on data from more than 34,000 participants across several countries and settings, the team ranked 661 gut species by how consistently they appear alongside healthy diets and favourable cardiometabolic markers, producing a top 50 and a bottom 50.
That ranking finally gives researchers a repeatable way to describe a health-associated microbiome, and it powers a score out of 1000 that accounts for both which bugs you carry and how abundant they are. Strikingly, several of the highest-ranked species are what Segata calls the dark matter of the microbiome: seen only through their genomes, never grown in a laboratory, and in some cases still unnamed. The second half of the paper moves from association to causation using two randomised controlled trials.
In the first, over 350 people followed either standard dietary guidance or a personalised nutrition programme, and the top 50 rose in both presence and abundance while the bottom 50 fell, some becoming undetectable. In the second, a whole-food prebiotic blend of over 30 plants produced a far larger shift than an over-the-counter probiotic or a bread-crouton control. Along the way the conversation covers polyphenols, resistant starch, soy isoflavones and menopause symptoms, and the surprising finding that most of our gut microbes originally came from other people.
Key quotes
4The top 50 is like the most wanted bacteria that we would all love to have in our gut.
There are some microbes that no one saw before us.
Your body is difficult to change, almost impossible. Our microbiome can be changed.
It's all about what you add into your diet rather than necessarily what you take away.
Key ideas
9Microbiome science needs enormous numbers
Two people share 99.9% of their human genome but only around a third of their gut species. That variability drowns weak signals, so only very large and geographically diverse datasets can separate real patterns from noise.
A top 50 and a bottom 50
Of 661 species abundant enough to analyse, the team ranked those consistently found alongside healthy diets and favourable cardiometabolic markers. The result is a most-wanted list of 50 and a least-wanted list of 50.
It is a health-associated microbiome, not a healthy one
Segata is careful with wording: the ranking describes microbes most associated with healthy human characteristics, because a healthy microbiome cannot be defined without reference to the body it lives in.
The dark matter of the gut
Many top-ranked species have only ever been seen through metagenomic sequencing, never cultured. Between 5 and 15% of the gut microbiome remains genuinely unknown, and much of the unknown sits on the good side of the list.
Good bugs are specialists, less helpful ones are generalists
The favourable species tend to ferment complex fibres and produce short-chain fatty acids and other beneficial compounds. The less favourable ones tend to thrive on simple sugars and lean pro-inflammatory.
A single score out of 1000
Combining which species are present with how abundant they are produces one number, where higher means more of the favourable bugs and fewer of the unfavourable ones. Until now there was no agreed marker of microbiome health at all.
Diet changed the microbiome in a randomised trial
Over 350 people were randomly allocated to standard dietary guidance or a personalised nutrition programme for 12 to 18 weeks. The top 50 rose in presence and abundance, the bottom 50 fell, and some became undetectable.
Whole-food prebiotic beat the probiotic in the trial
In a second trial with about 130 people per arm, a blend of over 30 plants produced a large rise in favourable species. The over-the-counter probiotic mainly moved the one bug it contained, and the control barely moved anything.
We collect our microbes from other people
Segata's separate work traced strains moving between babies, parents, educators and even pets. Children sharing a daycare room for a few months shared 10 to 15% of their gut microbiome.
Practical takeaways
6- 1
One fibre supplement is one fibre 52:00
A single isolated fibre feeds only a couple of species. Variety of plant material is what feeds a variety of bugs, so aim for diverse whole plants rather than one powder.
- 2
Chase colour as well as fibre 53:30
Polyphenols concentrate in deeply pigmented, often bitter plants, and around 80% reach the large intestine where microbes transform them. Different bugs handle different polyphenols, so range matters more than quantity of any one.
- 3
Think 30 plants a week, not one superfood 55:00
Diversity of plants is the simplest proxy for diversity of fibres and polyphenols, which in turn supports a wider community of favourable species.
- 4
Soy responses are personal 56:00
Some people carry bugs that convert soy isoflavones into a far more active compound, and in trials they saw around 75% greater reduction in menopause symptoms. If a supplement works spectacularly for someone else, that may be their microbiome talking.
- 5
Add rather than subtract 58:40
Directly removing unfavourable microbes is hard, but raising the favourable ones squeezes them out proportionally in a limited space. Focus the effort on what goes into the plate.
- 6
Cook, cool, then reheat your starches 1:00:00
Potatoes, rice and pasta form resistant starch when cooled after cooking, and it survives reheating. It is an easy way to feed favourable microbes from foods you already eat.
Topics & chapters
14Why this research matters
A rapid-fire opening establishes the core claims: gut bacteria are linked to long-term health, and unlike your genes, your microbiome can be changed.
Publishing in the world's most-read journal
Segata explains the weight of peer review, with five reviewers scrutinising the work from first word to last supplementary number.
Why scale and diversity of data matter
More than 34,000 participants across countries, cities and rural settings were needed to lift the signal above the noise of natural microbial variation.
Two papers in one
Berry frames the work as a snapshot showing diet-microbiome-health links, plus interventional data that moves the argument from association towards causation.
The top 50 and bottom 50 revealed
661 species were ranked by their association with healthy diets and cardiometabolic markers, producing the most-wanted and least-wanted lists.
The dark matter of the microbiome
Several high-ranked species have never been cultured and some are still unnamed, including one christened Segatella. Between 5 and 15% of the gut remains uncharted.
What makes a microbe favourable
Fibre-fermenting specialists produce beneficial compounds, while sugar-loving generalists lean inflammatory. Red meat and trimethylamine illustrate how bugs mediate food effects.
Turning complexity into a score
Types and abundances are combined into a single number out of 1000, giving researchers and individuals a comparable measure for the first time.
Clusters for inflammation, sugar, heart and body composition
Further work groups species into four health-relevant clusters so results can be fed back to people in an understandable form.
The first randomised trial
Over 350 people followed either standard dietary guidance or a personalised programme for 12 to 18 weeks, and the ranked bugs moved in the expected directions with statistical significance.
Prebiotic plants versus probiotic capsules
A second trial compared a 30-plus plant whole-food prebiotic, an over-the-counter probiotic and a bread-crouton control across about 130 people each. The plant blend produced by far the largest shift.
Microbes travel between people and pets
Daycare research tracked strains passing between babies, parents, educators and household pets, hinting that social contact underpins part of the blue zones story.
Fibre alone is not enough
Diversity of fibres and polyphenols feeds a diversity of bugs, which in turn produces a wider range of beneficial compounds.
Boosters, antibiotics and resistant starch
Specific foods can be matched to specific bugs, recovery after antibiotics is partly social, and cooled-then-reheated starches are an easy everyday win.