Microbiome’s “dark matter”: Landmark study ranks gut bacteria species based on health impact

In one of the largest microbiome studies to date, scientists have developed a system of ranking gut bacteria species based on their health impact, named the “ZOE Microbiome Health Ranking 2025.” While the system offers a compelling framework for clinical use, experts in the field debate whether the approach might be too reductionist to capture the complex, synergetic nature of the whole microbiome. 

Historically, the microbiome field has lacked large‑scale, comprehensive studies that explore these links in diverse populations. Drawing data from 34,000 US and UK participants, the new system ranks known and unknown gut microbiome species based on how closely they coincide with nutritious diets and cardiometabolic health.

The study authors found that ZOE proved highly reliable across more than 7,800 public samples, showing a consistent link between specific microbes, body mass index (BMI), and disease status.

Additionally, in clinical intervention trials involving 746 participants, it demonstrated the effects healthy dietary changes had on gut microbes. Over time, “favorable” species increased while “unfavorable” ones declined, establishing that a change in eating patterns can shift the species‑level composition of the microbiome, with knock‑on effects on host health.

Offering an independent perspective, Dr. Lindsey Edwards, a microbiology lecturer at King’s College London, UK, comments: “For some years now, scientists and clinicians have spoken about the importance of the microbiome, but we have had no real measures of what a healthy microbiome actually looks like.”

“This study is a landmark because, for the first time, we have an evidence-based idea of health. It provides a foundation for understanding microbial balance in ways that could transform both research and clinical practice.”

Complications in “good versus bad”

By leveraging diet scores such as the Healthy Eating Index or the Healthful Plant-Based Diet Index, along with health estimators, such as blood glucose, HDL cholesterol, and triglycerides, the study authors pinpointed microbial species that are expected to characterize hosts in healthier conditions.

Clinical intervention trials involving 746 participants showed healthy dietary changes boosted “favorable” species of gut microbes.They also identified other species that were abundant in hosts with more unfavorable health risk factors.

Experts not involved in the research express a mix of optimism and caution around the findings. One critique is that the study’s interpretation of “good versus bad” bacteria on the basis of association with health markers is an “oversimplification,” as Dr. Fred Warren, group leader at Quadram Institute, UK, argues.

“The authors exploit their large dataset to characterize the ‘microbial dark matter,’ previously unknown and uncultured bacteria that form a significant part of our gut microbiome and which may have a significant bearing on health and disease,” he says.

“All of these bacterial species are part of a normal, healthy gut microbiome, and their association with disease is complex and context dependent. There is much more research to be done before this work can be applied to making real-world decisions about health and dietary choices.”

Edwards echoes this sentiment, emphasizing that the study establishes associations — earmarking species that appear more often in healthier individuals or alongside certain diets — but cannot prove causality.

“We cannot say that the presence (or absence) of a particular species causes better health, nor that changing diet will directly lead to improved outcomes via the microbiome,” he underscores.

“To prove that, you need prospective cohort studies and interventional clinical trials where you deliberately change diet or microbiome composition and then measure health effects. While the study does not prove cause, it provides the evidence base needed to design trials that can test causality.”

Health beyond absence of disease

The introduction of the new system advances how we understand and harness the microbiome for long‑term well-being, which Edwards believes leads to “profound” implications.

He continues: “By defining health rather than just disease, this work opens the door to more precise diagnostics, improved regulation, and innovative therapies. It is a timely and constructive contribution to global debates on microbiome science and public health.”

In time, Edwards stresses that the ZOE Microbiome Health Ranking will need to be expanded to cover more globally diverse populations. “It is not simply about restoring microbial species but about restoring their functional and metabolic capability,” he notes.

“In other words, modulating the microbiome to improve health is not just about adding microbes back in, but about understanding how we can support them to flourish in ways that enhance resilience and strengthen our health.”

Solutions that feed the microbiome are growing in parity with probiotic solutions. Recently, Nutrition Insight sat down with Eline Verrijk, FrieslandCampina Ingredients’ marketing manager for performance and active nutrition, to discuss pioneering prebiotic innovations.

Furthering advances in the field, Danone recently opened its OneBiome Lab to fuel future commercial innovations for gut health. In an interview, Danone’s chief research and innovation officer, Isabelle Esser, shared her insights on new biotic product developments, targeting key research gaps.