Introduction

Living inside of you are trillions of microbes – and they’re vital for your health.

The gut microbiome has limitless potential to prevent and treat disease, and Quadram experts are delving into an ecosystem as dense as the Amazon rainforest to better human health.

But, what exactly is the gut microbiome?

Take a masterclass in microbes as we uncover this amazing microscopic world.

What is a microbiome

A microbiome is a community of microbes that live and interact together in a particular environment. You may be most familiar with the human microbiome, but it’s not only our bodies that harbour trillions of microorganisms. Animals, plants, soil and even oceans all play host to unique ecosystems of microbes.

More than 100 trillion microbes live on and inside your body, including your skin, lungs, mouth, and even your hair follicles. The densest and most diverse microbial community is in our gastrointestinal tract, and is known as the gut microbiome. As well as bacteria, the microbiome also includes other microorganisms including fungi, viruses, protozoa and archaea. Most of these microbes do us no harm at all, and some provide us with benefits to our health.

Microbes might be small, but they sure are mighty. Collectively, the human microbiome weighs approximately three pounds or 1.4 kilogrammes. Like us, each microbe has a genome, the collection of genes needed for it to grow and live. Whilst most individual microbe’s genomes are much smaller than ours, the collective genome (or meta genome) of all these microorganisms equals approx. 3.3 million genes. To put that into perspective, that is 100x more genes than there are in the human genome. Our gut microbiome is also as unique to us as our fingerprint; only 10-20% of genes are shared by two unrelated people.

How does the gut microbiome work

Microbes line the entire digestive system but mostly congregate in your intestines, collectively called ‘the gut’.

When we eat, our digestive system breaks the food down into small, easily-absorbed components. The large intestine breaks down fibre and complex carbohydrates. However, our large intestine has a limited digestive capability. The break down and absorption of most carbohydrates, proteins, fats, vital minerals and vitamins all predominantly takes place in the small intestine.

Here’s where are friendly microbes help out. The gut microbes need complex carbohydrates for their own nutrition and they source them either from our diet, or from mucus that lines our gut. In exchange for those nutrients, the gut microbes help us break down our food making nutrients available to us that would otherwise be lost.

For example, as a biproduct of food break down, gut microbes produce short-chain fatty acid like butyrate, which are vital for gut health. Without our gut microbes, substances that we can’t digest alone would be eliminated in our faeces (or our poo) without the full goodness in them becoming available to us.

What’s the difference between the microbiota and the microbiome

Often, the words ‘microbiome’ and ‘microbiota’ are used interchangeably. However, there are notable differences in their definition.

The microbiome describes both the ecosystem of microbes found in a specific environment and their genetic material. This collection of genes is known as the ‘Theatre of Activity’ (Whipps et al., 1988). The gut microbiome’s function or ‘activity’ can be beneficial or detrimental to gut health, depending on the species and genes present.

In contrast, microbiota refers only to the collection, or types, of different microbes found in a specific environment. Within the gut microbiota you can find bacteria, fungi, protozoa, viruses and single-celled organisms known as archaea. Find out more about our gut microbes and how they interact with us.

Probiotic Prebiotic and Faecal Microbiota Transplants

The composition of our gut microbial communities can be changed and improved using probiotics, prebiotics and Faecal Microbiota Transplants (FMT), and potentially harmed through the use of antibiotics;

A prebiotic is “a substrate that is selectively utilized by host microorganisms conferring a health benefit” (World Health Organisation {WHO}). Prebiotics act as food for the gut microbes and stimulates growth amongst pre-existing beneficial bacteria.

Probiotics are “live microorganisms that confer a health benefit on the host when administered in adequate amounts” (WHO).  The proposed benefits include: restoration of gut balance after dysbiosis, anti-inflammatory activity, competitive exclusion of pathogenic microbes, and stimulation of the immune system.

Faecal Microbiota Transplants (FMT), or ‘poo transplants’ as they are more commonly known, may sound nauseating, but this unconventional treatment can be a highly effective way of restoring a healthy gut microbiota. Faecal Microbiota Transplants (FMT) involves taking a sample of faecal matter from a healthy donor, screening it, and transplanting it into a recipient.

Antibiotics help stop infections caused by bacteria. They do this by killing the bacteria or preventing them from spreading. However, they not only act on infection-causing bacteria, but also the beneficial bacteria in the gut. As such, antibiotics can reduce the diversity of your gut microbes and cause your gut microbiota to become ‘imbalanced’.

How does food affect the gut microbiome

You are what you eat, particularly when it comes to your gut microbes.

Our diets can significantly impact the health and composition of the microbial community in our gut. A rich, varied source of nutrients and complex carbohydrates can help our microbes thrive. Complex carbohydrates and fibre that we can’t digest but that provides nutrition for gut microbes is termed prebiotic. A restricted diet and lack of nutrients can impede our gut microbiome’s health and even impact the growth of certain beneficial bacteria.

Want to help your beneficial bacteria flourish and prosper? Turn to fibre. The World Health Organisation recommended 30g of fibre a day. Despite this, adults in the UK only eat about two-thirds of the recommended daily intake. Soluble fibre has prebiotic properties, and eating the recommend 30g of fibre a day can help your gut microbiome produce more essential short-chain fatty acids.

For thousands of years, humans have manipulated microbes to preserve perishable food. Furthermore, foods can come with their own microbes that are beneficial to us. These are called probiotic foods, as they aim to deliver live microbes into the microbiome.

Dairy products like yoghurt, kefir and cheese; and preserved vegetables like olives, sauerkraut and pickle, are made with bacteria via lactic acid fermentation. Alcoholic fermentation is how yeasts convert sugars into alcohol, and is used for producing beer, wine and numerous baked goods.

Friendly moulds also reside in our food. Think of blue cheese, for example!

It’s important to note that not all foods containing live cultures meet the definition of a probiotic.

Where do we get our gut microbes from in the first place and do they change with age

Initial colonisation of the gut by microbes happens during and shortly after birth when infants are rapidly exposed to a whole plethora of bacteria, fungi and viruses. These may colonise for a short time, or for more extended periods. Until the age of 2-3 years, the early-life microbiome is constantly changing. Major factors affecting microbiome development include nutrition (such as breastfeeding or formula feeding) and the use of antibiotics and probiotics.

By the age of 2-3 years, we reach a relatively stable adult microbial community. Yet, our lifestyles can change the composition of our gut microbiome, for better or worse:

Our diet and nutrition.

Our exercise and movement.

Our levels of stress.

Our use of antibiotics.

Ageing also affects our gut microbial community. Physical factors that change with advancing age contribute to this and include: reduced movement and activity; dental problems that impede efficient chewing; and dietary changes. As we age, our microbiome changes and we see:

A lower abundance of some bacteria like Bifidobacterium species

More degradation of proteins and fewer short chain fatty acids

Continuous, low-grade inflammation (known as inflamm-ageing)

Increased susceptibility to infections

In a recent study by Dr Falk Hildebrand (Quadram Institute and Earlham Institute {EI}) and colleagues, they discovered how the microbes in our gut persist throughout our lifetime.

The research team re-examined all the genes present and their abundance from over 2,000 adult and infant faecal samples, including several from the same families. They showed that the different types of bacteria could be clustered into three major groups based on the strategies they used to persist in the human gut:

Tenacious Bacteria: The most persistent and well-adapted for survival in the human gut, but the most likely to be lost from the microbiome following antibiotic use.

Heredipersistent Bacteria: Strains that are ‘inherited’ and cluster within families. These have a lower persistence in childhood and a higher turnover rate, suggesting cycles of reinfection is key to their persistence in an individual.

Spatiopersistent Bacteria: These bacteria appear to cluster to their own geographic areas, but not are not associated families.

Opportunities for Health Our Research into the Human Microbiome

At the Quadram Institute, we want to understand the interactions between the microbiome and the human body, with the food we eat and with the wider environment.

Studying these interactions will give us a complete understanding of the role the microbiome has in health.

It will also point the way to new therapies to treat microbiome-related disorders or prevent conditions from developing, helping keep us all healthy throught life.

The Microbiome and Gut Health

Microbiome Establishment

The Hall Group, led by Prof. Lindsay Hall, looks into microbiome establishment during the early-life developmental window. Their focus is pregnancy and infancy, and whether the microbes that colonise during this time (e.g. Bifidobacterium species) coincide with stages in a child’s development, thereby building strong foundations for future health and wellbeing. Two large long-running  clinical studies interlink the group.

BAMBI Study

Necrotising enterocolitis (NEC) is a devastating bowel illness. The earlier babies are born, the more likely they are to develop NEC. Staff from QI and the Norfolk and Norwich University Hospital (NNUH) Neonatal Intensive Care Unit investigated whether routine supplements of beneficial bacteria (i.e. probiotics) could enhance the bacterial composition and function of the gut microbiota in pre-term babies. Read the case study to find out more.

PEARL Study

QI and NNUH researchers launched the PEARL Study to understand better the importance of beneficial microbes in the development of the infant microbiota. The PEARL study will help define microbial ‘signatures’ that are indicative of good health and could lead to new therapies that will promote health and prevent disease. Find out more here.

Interkingdom Cross-Talk and Host-Microbiome Interactions

Our researchers are particularly interested in interkingdom cross-talk and host-microbiome interactions – that is how microbes talk to each other – and to us from inside our gut.

In collaboration with Imperial College London and London North West Healthcare NHS Trust, Prof. Simon Carding and his team have compared this cross-talk in microbes in donated biopsy tissues from healthy people with the same tissue from patients with Inflammatory Bowel Disease (IBD). They found that Outer Membrane Vesicles (OMVs) produced by certain gut bacteria have a key role in cross talk and regulating the immune system which is altered in IBD.

To help translate the complex communication involved in crosstalk between the microbiome and the body, QI and EI researchers created MicrobioLink.

MicrobioLink is an integrated computer pipeline that connects microbial proteins with the host proteins they are likely to interact with, and then infers how these interactions influence cellular processes in the host. The tool is incredibly valuable for researchers trying to understand how microbes influence health, the changes that lead to disease, and to point to potential drug targets.

Changing the composition of the gut microbiome

At the Quadram Institute, our researchers are investigating how to manipulate the gut microbiome to improve human health.

QI and Jiangnan University researchers showed how different strains of probiotic bacteria differed in their ability to restore the microbiota of mice that had received antibiotics.

Working with NNUH and Dr Ngozi Elumogo, Prof Arjan Narbad and his team successfully treated C. difficile infections using faecal microbiota transplantation (FMT).

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The gut microbiome and human physiology

Dysbiosis

Dysbiosis happens when the gut microbiota becomes imbalanced, or ‘out of kilter’. The most common causes of an imbalance are a loss of beneficial microbes, excessive growth of harmful microbes, or a general loss of microbial diversity. Dysbiosis can lead to a wide range of digestive illnesses, including gut inflammation, inflammatory bowel disease (IBD) and colorectal cancer.

Our researchers are investigating the causes and effects of dysbiosis. Working with Prof. Chen Wei and colleagues from Jiangnan University in China, researchers in the Narbad Group discovered that a new sulphate-reducing bacterium (SRB) can convert nitrogen into a biologically useful form. Until now, SRBs have been commonly associated with digestive illness.

There are around 250,000 people in the UK with Myalgic Encephalomyelitis (ME), also known as  Chronic Fatigue Syndrome (CFS). It causes widespread pain, extreme fatigue, an inability to concentrate and for a large proportion of people, gut disorders such as Irritable Bowel Syndrome (IBS).

The Restore-ME trial, led by Prof. Simon Carding with NNUH, University of East Anglia (UEA) and funding from Invest in ME, is investigating the link between dysbiosis and ME/CFS. The study will test whether the use of Faecal Microbial Transplants (FMT) can restore the microbiome in ME/CFS patients and relieve symptoms.

Gut-Liver Axis

The gut-liver axis is an exciting area for research, particularly as we increasingly understand more about how the gut microbiome influences health. Cholestasis is a common symptom of chronic liver disease. Researchers have found that the microbiome is different and less diverse in patients with cholestasis. Some cholestasis patients also show signs of a ‘leaky’ gut, and inflammatory bowel disease. These associations give clues to how cholestasis develops. To investigate further, Dr Naiara Beraza led a study into the interactions between gut microbes and cells of the immune system that contribute to cholestatic liver disease.

Maintenance of a healthy gut microbiota

Understanding how differences in populations of bacteria and other microbes influences the functional role of the gut microbiome in human health is crucial. Gut bacteria break down carbohydrates using glycoenzymes; different bacteria have different types of glycoenzyme, each one being specific to a certain carbohydrate.

Prof. Nathalie Juge leads a team investigating these glycoenzymes, and how their specificity for certain carbohydrates suits them to different roles in the gut. The team identified an enzyme that helps particular bacteria colonise the human gut by giving them access to breast milk sugars and intestinal mucins. The Juge Group also discovered that the sugars in milk, called human milk oligosaccharides (HMOs), can improve ‘leaky’ guts.

In addition to the other benefits, a healthy gut microbiome also helps us fend off invading pathogens, the microbes that can cause disease. They can outcompete them for nutrition and space to colonise in the gut, preventing any invaders from accessing the gut lining and getting into our blood stream.

They also produce a range of compounds that inhibit pathogen growth, including Short Chain Fatty Acids (SFCAs) and bacteriocins (proteins that limit microbial growth) The Narbad group recently found a strain of Lactobacillus in human breast milk that makes an arsenal of bacteriocins and SFCAs that could be key to helping maintain a healthy microbiome.

The gut microbiome and breast cancer

Breast cancer is the most common type of cancer diagnosed in women in the UK, but the prognosis is good if diagnosed early. Although gut microbes seem like unlikely heroes in the fight against breast cancer, several studies have indicated that they can actually boost cancer therapies. They may also be biomarkers indicative of cancer progression that can be used to screen cancer patients.

The BEAM study, led by Nancy Teng, is one of the few trials so far that is exploring the gut microbiome and breast cancer.

Recent research shows that the gut microbiome influences the outcome of cancer therapy by modulating the host inflammatory response. This suggests a direct correlation between microbe-mediated immune reactions and the efficacy of a group of drugs called immune checkpoint inhibitors; these include the commonly used drug, pembrolizumab.

The groups of Prof. Lindsay Hall and Dr Stephen Robinson have joined a collaboration to investigate whether the microbiome can be used to predict how breast cancer patients will respond to immunotherapy. It’s hoped that this will help tailor future treatments, by personalising them for each patient.

The gut-brain axis
“Manipulating the microbiome is increasingly being seen as a way of improving or maintaining human health, and these results are an exciting indication of its potential for helping us age healthily”

Ever had a gut feeling? The gut-brain axis is the bidirectional network of signalling pathways between the nervous system and the gastrointestinal tract. Imbalances in the gut microbiome are often associated with immunological and neurological pathologies. The focus of much scientific research is how the microbiota talks to the brain.

The MOTION Study that the Quadram Institute is running with UEA is studying microbes in the ageing gut and their effect on mental health and cognition in people aged over 60. The MOTION Study will answer key questions about whether the age-related decline in cognitive function is associated with changes in the intestinal microbiome, and if so, what the nature of this relationship is and how can ensure maintain mental health is maintained as we age.

The Gut Microbiome and Cognitive Health

A poo transplant could one day be the secret of eternal youth. No, really. Research shows that the ageing process may be linked with age-related changes in our gut microbiome. A collaborative study involving the Quadram Institute, UEA, and the University of Florence showed how faecal transplants from older to younger mice altered their gut microbiome, impacting their spatial learning and memory.

“Manipulating the microbiome is increasingly being seen as a way of improving or maintaining human health, and these results are an exciting indication of its potential for helping us age healthily”

“We have established an FMT service on the Norwich Research Park to treat serious gut infections and now want to explore in humans its effectiveness in combating a number of age-related conditions, including cognitive decline.” Prof Arjan Narbad

The Gut Microbiome and Parkinson’s Disease

Parkinson’s disease is a progressive condition that affects the dopamine-producing nerve cells that coordinate movement. As more nerve cells die, less dopamine is produced, leading to gradually worsening tremors, slower movement and muscle stiffness.

Many people with Parkinson’s disease also have gastrointestinal problems that become evident several years before the more typical movement-associated symptoms. They may also have inflammation and a ‘leaky’ gut – all signs of an imbalanced gut microbiome.

Researchers from the Quadram Institute did a meta-analysis of the gut microbiome in Parkinson’s disease, which provided the clearest picture to date of the changes associated with the condition.

By re-analysing data from ten different studies, a common pattern of differences in abundance of particular gut bacteria in Parkinson’s disease emerged, suggesting that these alterations in the gut microbiome might trigger some of the gastrointestinal problems seen in patients.

“The variability across studies is very big. However, we can still detect differences between the gut microbiome of patients and controls. This means that microbiome alterations in Parkinson’s disease are consistent across sampling cohorts.”

“There is a clear need to further research gut microbial changes linked to diseases in diagnostic or prognostic applications.” Study Lead Dr Stefano Romano

Free Resources on the Gut Microbiome

Free FutureLearn Course on the Human Microbiome

Want to learn more about the human microbiome? Experts at the Food Databanks National Capability, based at the Quadram Institute, teamed up with EIT Food and The University of Turin, alongside CSIC, University of Reading, and Microbion to bring you a groundbreaking course, available for free on FutureLearn.

The course investigates how the microbiome changes throughout our lives, the role of food in this, and the functions the microbiome has in the gut in everyday life. Over three weeks, you’ll explore three areas:

  1. The Journey of Life – what the gut microbiome is composed of, what its functions are, how it changes during a lifetime and how it can be analysed
  2. The Journey of Food – how food is processed in our gut, concepts about probiotics and prebiotics and how they influence the gut microbiome
  3. The Journey from Healthy to Unhealthy – how the close connection between our microbiome and the status of our health can influence the onset of human disease

Register for free here.

Free Online Lecture

Want to find out more about the gut-brain axis? In 2015, Prof. Simon Carding described the relationship between the gut microbiome and what goes on in the rest of our body. He also introduced the provocative idea that gut microbes influence when, what, and how often we eat – and whether we stay healthy or succumb to disease. The lecture has been viewed over 2 million times already!

Best Practise in Gut Microbiome: A Guide for Academics

In the spirit of fostering collaboration and sharing expertise the Quadram Institute has compiled a Best Practice in Microbiome Research website. Our researchers have collaborated to produce a series of free-to-access state-of-the-art protocols that have been developed, optimised and applied to microbiome studies across the Quadram Institute. This will continue to develop over time, mirroring the rapidly evolving field of microbiome research.

quadram.ac.uk/best-practice-in-microbiome-research/

Teaching children about the gut microbiome

Need some help teaching children about the gut microbiome? Our scaled-down superheroes are here to help! Meet the Guardians of the Gut.

Guardians of the Gut is an exciting new resource for children to learn about the importance of their gut microbes. Our fun activities explain the different organs within the human body, introduce key microbes and the beneficial jobs they do, and explores how invading bad bacteria and antibiotics can upset the balance. Take the pre- and post-lesson quizzes to see your children grow in knowledge, download award certificates for your class and enter your school in a prize draw to win science goodies!

Enrol your school for free here

Build your own gut microbiome with the official British Science Week 2021 Primary Activity Packs.

What does the gut microbiome do for us - A Summary

Keeping a stable, healthy gut microbial population is mutually beneficial – it helps us and the microbes. In exchange for nutrition and a comfortable habitat, the microbe community returns the favour by providing us with health benefits, which we are now starting to understand;

  • Digestion of food and complex plant-based polysaccharides (fibre)

  • Development of the immune and enteric nervous systems

  • Infection resistance and warding off viruses and pathogens

To find out even more about our microbiome research, read more case studies, meet the researchers and catch up on the latest microbiome news from the Quadram Institute, see https://quadram.ac.uk/targets/understanding-the-microbiome/

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