A microbiome is a community of microbes, including bacteria, viruses, fungi and other microorganisms that live and interact together in an environment.

Microbiome research is constantly developing to learn more about which microbes are living together in different places and what they do and how they interact with our body in both good and bad ways.

There are lots of different ways we can study microbiomes and together these help us learn more about gut microbiome, skin microbiome and other microbiomes too.

Our researchers recently published a freely available book on the Best Practice in Microbiome Research. They published the book to help promote a more standardised approach to studying microbes because sometimes translating microbiome research into the clinic has been challenging due to a range of different approaches, making studies difficult to reproduce, or combine to develop a holistic picture of how microbes influence health

Here we highlight some of the methods and topics featured in the book.

Human studies to collect microbiome samples

One of the main ways we study microbiomes is by undertaking human studies.

Some human microbiome studies are observational, which means researchers look at how natural microbiomes vary between people. Observational studies look at a specific group of people and observe how microbiomes change over time too.

We previously ran the MOTION study which was an observational study in people aged over 60, providing microbiome samples over four years. The study investigated gut microbes and the role they may play in healthy ageing and declining mental health and the risk of developing dementia. Another observational study we ran at the Quadram Institute was the Pregnancy and EARly Life study (PEARL) study which collected microbiome samples from 261 mothers and their babies from pregnancy through to early life to learn more about how the gut microbiome is first established and how it impacts on early life.

Other types of human studies we run at the Quadram Institute are dietary intervention studies which involve people eating certain foods or dietary compounds. Some dietary intervention human studies may include observing microbiome changes after dietary changes.

Across all human studies, it’s important that each study includes enough people and samples for statistical analysis. At the Quadram Institute, our experienced Statistician provides expertise and advise on study design and statistical analysis so that results from human microbiome studies are both robust and reliable.

It is also important that human microbiome studies follow ethical principles and regulations too and our human studies team ensure that all our human studies follow these.

Poo and other samples to capture the microbiome

One way we can study the gut microbiome is by looking at microbes found in poo, or faecal, samples. They provide an easy noninvasive way of looking at gut microbes. Faecal samples can be collected at home by people taking part in research or donated in a clinical environment, such as our Clinical Research Facility.

Other samples we sometimes use at the Quadram Institute to study microbiomes are skin, oral, nasal, vaginal and colon samples.

Skin, oral, nasal and vaginal samples are usually collected on swabs by those taking part in research and like faecal samples, can be collected at home and mailed in or, at a clinical research facility.

Colon samples come from biopsies, collected during endoscopy procedures. Here at the Quadram Institute, we are home to one of Europe’s largest endoscopy centres.

DNA sequencing of microbiome

Once microbiome samples have been collected, culturing or gene sequencing allows researchers to identify microbes in the samples.

For gene sequencing, researchers extract the DNA or RNA from samples using different methods based on whether it is a faecal, nasal, oral, skin, colon or other microbiome sample. The method for DNA or RNA extraction may also vary depending on whether researchers are looking at bacteria, fungi or viruses.

Once researchers have extracted the DNA or RNA it can then be sequenced using a variety of techniques. Short-read metagenomics is a low-cost DNA sequencing approach which is useful for anaylsing complex samples with a mix of microbes in it, commonly referred to as metagenomics. Higher resolution long-read metagenomic sequencing is helpful for identifying previously undiscovered microbes. Researchers may use a mix of these two DNA sequencing approaches, along with RNA sequencing and metatranscriptomics to identify the genes that are functional and expressed by  microbes in a microbiome sample.

Here at the Quadram Institute, we have a dedicated Sequencing team who provide our researchers with fast and efficient sequencing services using both methods.

Bioinformatics to build understanding of what microbes are in samples

After sequencing the next step to study microbiomes is to use bioinformatics to analyse and make sense of the sequence data. To achieve this, bioinformaticians use various computational methods, software tools, and mathematical models to, for example, check DNA quality control and determine its source in a sample. A challenge to microbiome anaylsis is that these tools and software are always changing which can complicate and limit comparing results between different microbiome studies.

Key to addressing this is making sure that bioinformatics tools used to anaylse DNA samples are documented under the FAIR principles. FAIR stands for Findable, Accessible, Interoperable, and Reusable).

At the Quadram Institute, our dedicated Bioinformatics team support scientists in using bioinformatics software and tools and champion the use of the FAIR principles.

Mapping microbial metabolites to understand the role of microbes

Another way we can study microbiomes is through looking at the what the microbes are producing and secreting into the gut by analysing the metabolites in samples. Microbial metabolites are small molecules produced, used, or broken down by microbes and their analysis is referred to as metabolomics. Metabolomics enables us to learn more about what microbes are doing and the impact the metabolites they produce have on human health.

The human gut microbiome is a complex ecosystem that contributes to human health by transforming dietary nutrients and by producing essential micronutrients such as vitamins. Many of the interactions between microbes and human cells are mediated through the action or exchange of metabolites.

Metabolomics methods include liquid chromatography-mass spectrometry and nuclear magnetic resonance. Liquid chromatography-mass spectrometry involves separating molecules in a sample and then measuring the molecules. Nuclear magnetic resonance looks at the atomic properties and unique fingerprints of each molecule in a sample to determine which ones are present.

Key metabolites with health promoting properties include short-chain fatty acids which are an important energy source for the cells that line the gut wall.

Combining methods to get a more complete understanding of microbes

Another way of studying microbiomes outside the body is by culturing microbiome samples under conditions that mimic those in the human gut. Our Colon Model Facility has different fermentation systems that allow researchers to understand how individual, or populations of gut microbes interact as part of the gut microbiome.

We are also developing a metaproteomics capability to study the proteins produced by gut microbes and by the microbiome in general.

By combining different ‘omics methods, we can build a completer and more accurate picture of the gut microbiome and how it functions which is essential to understand the factors that may promote beneficial or harmful change its structure or function, and therefore how it affects our health.