Immunity Human Clinical Studies
The human microbiome and its interaction with the immune system is a well researched topic. However, past knowledge seems to become outdated.
Dr. Liam O'Mahony and Dr. John MacSharry, researchers at APC Microbiome Ireland and research partners of Atlantia take the stage for this in depth webinar. Discussed is the relationship between the microbiome and common viruses, allergies, and chronic diseases while also touching on what influences microbiome development in the early years of life in this online presentation.
What is known about the relationship between the microbiome and the immune system?
We know that the majority of cells in the human body are not human at all. According to Prof. Ruth Ley, director of the department of microbiome science at the Max Planck Institute, roughly 57% of cells in the human body are microbial encoded. In order for the immune system to tolerate this wide variety of foreign antigens to the body, it must have very potent tolerance mechanisms.
It is believed that many signals coming from the bacteria also drive tolerance signals. Many cells are responsible for the tolerance response both from the innate & adaptive immune system that are used to promote B-regulatory cells and T-regulatory cells (Sampson et al., 2018).
Microbial changes association with allergies and asthma
It is known that on sites such as the skin, in the gut, and lungs the composition of the microbiota is very different, associated with dermatitis, asthma or a food allergy for example. In some cases, these differences are present before the diagnosis of the allergy or asthma (Huang et al.. 2017). Perhaps some of the missing microbes or changes in microbes at these body sites may be contributing to the induction of allergy or asthma.
What influences microbiome development?
Numerous factors are important for the acquisition and development of a full adult-like community structure of the infant microbiome, particularly in the first two years of life. Many exposures that we know are important for microbiome development are also important risk factors for the development in allergies and asthma. Diet in particular has a significant effect on not just the composition, but also the metabolic activity of microbes in the gut (Lunjani et al., 2018).
One of the dramatic changes in the gut microbiome from a dietary point of view is with the introduction of non-digestible fibres (fibres we cannot digest, that microbes in the gut can). This digestion or fermentation results in the generation of short chain fatty acids like Butyrate, Propionate and Acetate (Roduit et al., 2019).
In a study conducted by Dr. Liam O’Mahony and colleagues, faecal samples from a 1-year-old children from a birth cohort study were examined. It was found that kids with the highest level of Butyrate and Propionate at 1 years-old had the lowest levels of asthma and a range of different allergies and allergy sensitisation by the school age of 6. This was correlated with early life consumption of yogurts and vegetables. Using mechanistic and experiments models, it was found that at least part of this protective effect was due to the induction of regulatory T cells.
The human lung microbiome
As mentioned previously, the lung microbiome is slightly different to the gut in that the biomass of the microbes is much less and to directly sample the lung you have to get a bronchoalveolar lavage which is a particularly invasive procedure. When conducting a lavage you are looking at the immune cells in particular, such as the macrophage, neutrophils and eosinophil.
When a subject has a lack of information in their lung you will find that the majority of cells are microphagous. However, when there is inflammation, be it a TH1 which is a neutral mediated inflammation, or a TH2 which is acidophil mediated, an increase in these cells to lung wash is found. This then results in a reduction of the market finished counts, suggesting immune activation in the lung, especially the peripheral lung.
Dr. John MacSharry and colleagues at APC Microbiome Ireland conducted a patient cohort, mainly from the South of Ireland in the Munster region, and found that many of the samples have very high levels of bacteria, fungi and virus’. Upon further examination of biopsies it was found that there is a lot of bacteria adhered to the microbes and to the epithelial also. The bacteria found in these locations are evading the Mucociliary Escalator and surviving inside the lung.
Lung Microbes: Fungi and viruses
Using Illumina WGS (Shotgun Sequencing), MacSharry et al. (2019) found that several patient samples had many virus’ present, mainly bacterial virus’ such as fasciitis. However, human virus’ were also found which can be called Lymphocryptovirus, and also many fungal sequences present. Unfortunately, fungal databases aren’t as developed, which creates difficulty when trying to find strain specificity by Shotgun Sequencing. This results in the need to move up to species level to find it.
The future of lung microbiome research
The lung microbiome is extremely important from the perspective of lung disease such as asthma and chronic obstructive pulmonary disease (COPD). However, the effects of Covid-19 on the lung and long-term immunity are unknown, it can be conceptualised that there will be changes to the microbiome, causing aggravation, particularly in asthmatics. Professor O’Mahony and colleagues research at APC Microbiome Ireland will be more focused on establishing a link between the gut and the lung.
When studying the microbiome in either the gut or lung, microbial changes can be strain dependant rather than being Bifidobacterium, suggesting the need for targeted therapies to understand what species are actually changing. Much of the research at APC Microbiome Ireland has led to anti-inflammatory and phage therapies.
The next step according to Prof. John MacSharry is to culture the many microbes that have been identified, some of which will allow for the development of microbiome diagnostics and designer phage therapy and possibly metabolic supplementation to disrupt these bacteria i.e. haemophilus influenza.
Chief Commercial Officer at Atlantia, Barry Skillington will guide you through the stages of a clinical trial at Atlantia from study design to conduct and reporting in the Immunity Webinar. He will demonstrate Atlantia’s experience in conducting trials on immunity and inflammatory health.
Atlantia has experience in inflammatory disease such as IBD, and testing inflammatory biomarkers using a disease activity index. Lastly, Barry will speak on immunity/infection, such as URTI, H. Pylori and antibiotic associated diarrhoea, along with a discussion of the range of measurements which can be utilised, depending on the desired outcome of a study. Visit our clinical expertise areas and our research services to learn more.