Summary Experts Meeting Human Microbiome & Applications in Therapies
On March 19th, 2021 BaseClear has organised an online experts meeting on Human Microbiome & Applications in Therapies. With 100+ attendees, this public event was …Read more
Personal microbiome test kits give consumers fascinating insights when they explore their gut microbiota. MyMicroZoo is a biotechnology company located in Leiden Bio Science Park in The Netherlands that offers consumers an unique opportunity to examine their gut bacteria. Established in 2016, MyMicroZoo was co-founded by Dr. Derek Butler, Dr. Tom van den Bogert and Dr. Jos Seegers, to provide consumers with the most up-to-date information on how the gut microbiota is shaped by lifestyle and nutrition, and its link to our health and well-being. Currently, MyMicroZoo has a large customer base that they are using to construct a population microbiome database.
Dr. Radhika Bongoni, Head of Business Development at BaseClear, interviewed Dr. Eline Klaassens, Product Manager Human Health, at BaseClear and the co-founder and Chief Scientific Officer of MyMicroZoo Dr. Jos Seegers about the gut microbiome, its relationship to human health, and the perceptions of both industry players as well as end consumers, and how genomic technologies are revolutionising the future of health diagnostics.
JS: “Derek Butler and Tom van den Bogert from BaseClear and I started the company together. I was personally curious about my own gut bacteria, and we thought it would be a fantastic idea for a business to bring gut microbiome measurements to the public. From the outset, Derek was involved because we needed the analysis infrastructure that BaseClear provides. We participated in a competition for start-ups at Life Sciences@work that helped us to shape our business plan and get started. We had slow but steady growth for a few years. It turns out that people are not so much interested in knowing their own gut microbiota as we expected, but rather they want to know what they can do to influence their gut microbiome, and how it relates to their health. We’ve now teamed up with medical doctors and dietitians to help people taking the test to interpret the results and translate them to lifestyle changes. That will be our focus in the coming years.”
RB: What is the relationship between MyMicroZoo and BaseClear?
JS: “When we started, it was important to have the infrastructure to handle the sequencing. BaseClear was a great support, as they have excellent analysis capabilities. They were also located very close to us, which made communication very easy. This meant that we didn’t have to invent the entire infrastructure and logistics surrounding the analyses from the start.”
JS: “It’s very important to help consumers understand how the microbiome works so that they can place the test results in context. At MyMicroZoo, we give a ‘masterclass’ and workshops to our customers and clients, the majority of whom are dietitians, nutritionists, medical practitioners and physical trainers, to help them to interpret the microbiome results for consumers. This background information provides insights into the microbiota, how to influence it and its effects on wellbeing before consumers receive the test results, so it’s much easier for the consumer to understand what is going on once they receive their report.”
EK: “At BaseClear, our clients come to us for microbiome profiling as well as metagenomics and metatranscriptomics. With the last two tools, you not only get insight into the diversity of your microbiota but also what functional capacities the microorganisms have and which functions are active in your stool. Our clients have background in science and health and are interested in probiotics, diets or the effect of pharmaceuticals on the microbiome. Samples come from larger pre-clinical and clinical trials and require advanced statistical analysis which we also provide at BaseClear. These analyses support data interpretation of complex datasets and answer the research questions of our clients. We also present the results in figures and tables that can be directly used for publications”.
JS: “It is a challenge to present complex scientific topics in a way that is understandable to the lay person. Visualisation is key to helping people understand things. Visualising the situation always makes it easier to see what’s going on. When dealing directly with MyMicroZoo consumers, who may not be as familiar with key scientific concepts, we need to present the information clearly and simply. The better you visualise concepts, the more understandable they become. We try to present the information visually as much as possible in our reports for consumers.
When we started, we had to think how the formatting of the report and the website would help make the analysis approachable. Consultation with customers and dietitians has been very important to improve our existing communication material and make the customer experience better. This is an ongoing process.”
EK: “At BaseClear, our customers usually have a scientific background, and the results are used for scientific studies. If people want to publish in an external journal, the visuals need to be quite catchy. Even though our clients often have knowledge of microbiology and scientific concepts, they are not always microbiome experts therefore the way we report back has to be easy to use for non-experts. Our clients like the interactive tools like Microbiome Explorer that we provide. The tool allows customers to play around with the data and develop suitable figures for publications. It’s a good way to link research questions and results all together.”
RB: “This clearly exemplifies the level of knowledge between clients. B2B companies like BaseClear extend solutions to other businesses (branding companies) who offer provide science-backed products to their end-customer, i.e., consumers like all of us. While B2C companies like MyMicroZoo extend simplified information directly to consumers. Of course the level of detail also varies between B2B and B2C approaches with microbiome dataset.”
EK: “The main challenges for us are related to how we can help our customers find the real impact of an intervention. We have to ask: what are the key components within the microbiome that are important and that we can link to the trial questions? We need to identify key species and link them back to biological function.”
EK: “Currently, we look for taxonomic identifiers within the microbiome. For example, specific strains. In the future, we will have full genome information of bacteria in the sample, and this will allow elucidation of full pathways that are changed by the intervention. This will allow explanation of the mechanisms involved to support further directed research.
It’s favourable to have different databases to answer different questions. We need to know what the question is to get the best results out. For example, our infant database includes strains relevant to infants including the major probiotics in infant formula. The results will be better if we use the right database for a specific research question. This approach also allows us to classify the microbiome at a higher resolution (at the strain level).”
JS: “We use 16S ribosomal mRNA sequencing, which provides genus-level classification. At the moment, we are looking at shallow shotgun sequencing to look for particular biomarkers, such as those for colon cancer. The cost of shallow shotgun is currently prohibitive for individual consumers, although the price is likely to decrease in future. When microbiome analysis becomes the standard of care and mainstream, then it will give more possibilities to use the data for diagnosis or to suggest more targeted treatments.”
JS: “I have never seen a study showing that increased diversity has negative health effects. Variability in the microbiome is always present, and diversity is based on the balance of those bacteria. The more different types of bacteria, the more resilient the microbiome is and the better it can prevent infections.”
“In the first 2 to 3 years of our lives, the microbiome is shaped and then stabilizes and reaches a (mostly) steady state that remains constant through the rest of life. And everyone has their own personal microbiome – someone else’s microbiome is not as good. We can lose bacterial diversity due to antibiotics or lifestyle changes. Perhaps in future we will be able to preserve this diversity we find in young children and “reinoculate” ourselves with our own microbiome at a later age.”
EK: “With a good targeted database, it’s possible to identify bacterial strains. This is important because strains from the same species are very similar yet there are differences in their functionality. Tools are available now that allow us to search through the meta-genome data and find strains that have not yet been cultured. Metagenome information can be used to select the bacteria of interest. For example, we can use selective media based on the known function of genes in the database and selectively culture it using ths information at a later stage.”
JS: “Escherichia coli is a good example. We all have E. coli species in the gut. However, only a few strains are clinically important. The O157 strain, and strains implicated in colon cancer are pathogenic, but the others are not. So it can be important to identify bacterial strains.
In addition to looking at strains, bacterial function is also important to map out in the microbiome. Butyrate-producers are a great example, because there are many bacterial species and strains that produce butyrate, so that functional pathway is important to investigate. The bacteria that are contributing are less relevant than the actual production.”
JS: “We have a general MyMicroZoo database. When customers receive their kit, they are invited to register it and fill in a questionnaire at the start that covers general health, diet and lifestyle. We now have a lot of samples, in the thousands, with meta-data and questionnaire data. We can use the database to correlate microbiome characteristics with health and lifestyle factors. This helps us to advance the science of microbiome research. Within the MyMicroZoo website, you can compare yourself to other groups, for example based on activity levels or BMI.”
EK: “A custom database improves the resolution of taxonomic profiling from genus or species level to the strain level. Which is very important for clients since research has shown that strains belonging to the same species that can have very different phenotypes and functional properties. For example, we have developed such a database for analysis of infant microbiome samples. This tool was thoroughly validated with appropriate datasets and shows significant improved taxonomy selection compared to our standard database. We are also in the process of making databases for other hosts (such as rumen and chicken) or other kind of sample locations (e.g. skin microbiota). We can also include additional strains for clients with interest in specific strains, such as their own probiotic strains. These advanced databases also reduce the number of unclassified reads in the results (Bongoni and Maciej).”
JS: “Based on our experience, we can see broad trends in diet and lifestyle based on someone’s microbiota. For example, stool type is linked to faecal transport time, and this determines the type of bacteria you will find in the stool. Depending on your microbiome, you will respond differently to different types of food. Both Prevotella and Bacteroides are common human gut microbiome inhabitants and dietary fibre fermenters. Prevotella tends to dominate the microbiome in non-industrialised populations while Bacteroides is more prevalent in Western societies. Prevotella is associated with certain health benefits. People in Western societies can eat a lot of fibre to increase their proportion of Prevotella, but this seems to come at the expense of diversity.”
JS: “Every day, we see more and more evidence that certain conditions are related to certain bacteria. Some examples include diverse conditions such as irritable bowel syndrome and depression. Chronic depression is linked to the absence of a particular bacteria. Can we make a probiotic to give people that bacterium to “cure” depression? It has not been tried yet, and we don’t know yet if it is correlation or causation, but it could be an interesting and useful research angle. Other examples are in drug metabolism. We know that the activity of certain medication can be reduced because of metabolism by gut microbes. But this does not happen for everyone: it’s highly dependent on the personal gut microbiome. In the future, when everyone has their own microbiota profile, we can see if medication can be given to certain people based on whether it will be affected by the gut microbiota. At the moment, this is not possible but in the future it could be useful.”
Bongoni R., Maciej C. The role of nutrition in the development of the infant microbiome. https://www.baseclear.com/blog/microbiome/the-role-of-nutrition-in-the-development-of-the-infant-microbiome/
Chen T, Long W, Zhang C, Liu S, Zhao L, Hamaker BR. Fiber-utilizing capacity varies in Prevotella- versus Bacteroides-dominated gut microbiota. Sci Rep. 2017;7(1):2594. Published 2017 Jun 1. https://doi.org/10.1038/s41598-017-02995-4.
Metatranscriptome data analysis: the next level https://www.baseclear.com/blog/bioinformatics/metatranscriptome-data-analysis-the-next-level/
Precup G, Vodnar DC. Gut Prevotella as a possible biomarker of diet and its eubiotic versus dysbiotic roles: a comprehensive literature review. Br J Nutr. 2019 Jul 28;122(2):131-140. https://doi.org/10.1017/s0007114519000680