Six facts about the gut microbiome

The gut microbiome is often described as difficult or even ‘unculturable’, but this is largely a misconception. In reality, many gut microbes can be grown in the lab, and the challenge lies in methodology and biology. This is a key focus of Bonface’s PhD, where he is working to overturn this assumption by improving how gut bacteria are isolated and studied.

“A major challenge is that many bacteria currently considered ‘uncultured’ require specialised growth factors such as vitamins, bile acids or metabolites produced by other microbes that are absent from standard commercially available culture media. Others occur at such low abundance in the gut that they may not be detected by shallow metagenomic sequencing approaches. Together, these limitations can lead to an underestimation of the true microbial diversity in the gut.” – Bonface Gichuki, PhD student

However, with improved cultivation techniques and targeted culture strategies informed by metagenomic data – the sequencing and analysis of microbial DNA from a sample – previously difficult-to-culture microbes can increasingly be isolated and studied as live organisms, enabling direct investigation of their functions in the gut ecosystem.^1,2

We all love a holiday – getting a break and travelling to see other parts of the world – and our microorganisms are no exception. The only difference is, they do not have to pay for the flight or accommodation.

As we move between countries, our microbiome travels with us, at least initially, reflecting our diet, environment and daily exposures. However, this community is highly dynamic and can shift rapidly in response to new foods, hygiene conditions and local microbial environments. Studies of international travellers show that gut microbiome composition can change within days of arrival in a new country, alongside the acquisition of new strains and diet-associated shifts. Travel can also be associated with digestive upset, such as bloating or traveller’s diarrhoea, which likely reflects a combination of dietary change, exposure to unfamiliar microbes and a temporarily disrupted gut ecosystem adjusting to new conditions.^3,4

At the same time, some gut microbes are adapted for human-to-human transmission and can form spores, allowing them to survive harsh conditions outside the body, as shown by research in Trevor’s group at the Institute. This expands transmission beyond direct person-to-person contact to include environmental routes, where microbes are released in respiratory droplets or aerosols, persist on surfaces or in dust, and are later picked up by another host. This highlights transmission as a key evolutionary force shaping the gut microbiome, with humans continuously sharing and reshaping each other’s microbial communities through everyday movement and contact.^5,6

 The Lawley Group at the Sanger Institute.

Image credit: Tian Tian/Wellcome Sanger Institute

While on the theme of travel, we are all familiar with the uniqueness of our fingerprint, which is increasingly being used in travel documentation – something that British people have had to become more accustomed to recently… Interestingly, we also all have our own microbiome fingerprint – a community of microorganisms that is shaped by who we are, where we live and how we live. Someone from Kenya like Bonface will have a very different microbial signature to someone from England like me, reflecting differences in diet, environment and early-life exposures. While there are shared core microbes that can be transmitted between people, much of this fingerprint is built early in life, particularly in the first months and years when the microbiome is most plastic.

Factors such as breastfeeding versus formula feeding, mode of birth (vaginal delivery versus C-section), and household and environmental exposures all strongly influence which microbes establish and persist. These early differences matter because this is also a critical window for immune system development. Once this period passes, the microbial community becomes more stable and harder to fundamentally reshape. As a result, early-life differences in microbiome fingerprints can have long-term effects on health, including altered risk of conditions such as allergies, asthma and metabolic disease.^7,8

In the last decade, several research groups reported the presence of a microbiota – a community of microorganisms – in the human foetus, including signals detected in studies of meconium, the newborn baby’s first stool. These findings generated considerable debate, as the idea of a prenatal or in utero microbiome conflicted with long-term understanding of early human development and would have major implications for immunology and clinical medicine.

To resolve this, a group of leading microbiome scientists, including Trevor, in 2023 systematically reviewed and harmonised existing datasets, re-examining evidence for microbial signatures in foetal samples. They found that many of the reported signals were more consistent with contamination from DNA extraction kits and reagents rather than true biological colonisation. The consensus conclusion was that there is no convincing evidence for in utero colonisation; instead, microbial acquisition begins at birth. This has now become the accepted view in the field, alongside broader recognition that claims of other proposed ‘sterile sites’ microbiomes, such as in blood⁹ or brain¹⁰ of healthy individuals, are also likely driven by contamination rather than true resident microbial communities.¹¹

Products upon products claim they will give you a ‘healthy’ gut microbiome, but what is considered healthy is still not well defined. What is healthy for one person may not be healthy for another, which is reflected in the fact that we each have a distinct microbial fingerprint shaped by diet, environment and early-life exposures.

We do know that certain bacteria are clearly harmful and can cause disease – for example, Vibrio cholerae, which causes cholera. However, beyond these obvious pathogens, defining and manipulating ‘health’ in the microbiome is much more complex, which is one reason microbiome-based therapies remain challenging to develop.

A major issue with commercial probiotics is that they typically contain a small number of labelled ‘beneficial’ species. Yet when individual gut microbiomes are sequenced, these organisms are often rare or even absent in many people. This means probiotics are effectively introducing a small number of microbes into a highly competitive and complex ecosystem where they may not naturally belong and are therefore unlikely to persist or colonise long-term. For a microbial intervention to be effective, it likely needs to use strains that are already present or well-adapted to the existing gut community, so they can stably integrate and function within that environment.^12,13

More broadly, this reflects a deeper challenge in the field: what is ‘healthy’ is context dependent. While approaches like faecal microbiome transplant (FMT) – the transfer of processed stool from a healthy donor into a patient’s gut to restore the microbial community – have been explored, they raise significant practical and ethical considerations. As a result, alternative strategies involve supporting the existing microbiome through diet, particularly plant-based, fibre-rich foods that gut microbes can feed on and produce compounds that are beneficial to gut health.¹⁴

One of the most important aspects of the gut microbiome – and a major driver of research interest – is its role in health and disease. Gut microorganisms perform several essential functions including metabolising food, protecting against invading pathogens, producing vitamins and helping to regulate the immune system.¹⁵ The gut is home to approximately 38 trillion microorganisms – roughly equal to the number of human cells – which can affect biological processes through different mechanisms.¹²

However, this ecosystem is highly delicate. Its balance can be disrupted by external factors such as diet, antibiotics or environmental changes, leading to dysregulation and disease. Increasing evidence links microbiome imbalance to a range of conditions, including inflammatory bowel disease, where altered microbial communities are associated with chronic inflammation of the gut.¹⁵ Associations are also being explored in respiratory diseases and cancer. For example, Professor Mike Stratton’s group in the Somatic Genomics programme is investigating colibactin, a toxin produced by certain strains of Escherichia coli. This toxin can directly damage DNA and is thought to contribute to the rising incidence of early-onset colorectal cancer.

The gut is far more than just a digestive organ. It is a dynamic and complex ecosystem that plays a central role in our overall health. From shaping our immune system in early life to adapting rapidly during travel, our microbiome is constantly interacting with our environment, diet and the people around us. Research at the Institute led by Trevor’s team is helping to challenge long-standing assumptions and deepen our understanding of this hidden world. While we have uncovered fascinating insights, many questions remain. What is clear, however, is that this microbial ‘workshop’ inside us is constantly busy – adapting, rebuilding and responding – making it one of the most fascinating and dynamic systems in the human body.