Deciphered to Combat IBD, Gut Microbiome "Chatter"

Deciphered to Combat IBD, Gut Microbiome "Chatter" ...

Scientists at the Earlham Institute, the Quadram Institute, and the University of East Anglia on the Norwich Research Park have developed a new computational biology technique to better understand IBD for targeted clinical interventions. The study uses cell crosstalk to identify how beneficial bacteria can be infected with our immune system to treat IBD and reduce gut inflammation.

Inflammatory Bowel Disease (IBD), a life-long chronic illness that has experienced sporadic bouts of gut inflammation, is affecting around 1 in 400 people, and is the most common type of IBD. Current therapies are ineffective and serious detrimental to the health of the patients and their families.

The human gut maintains a group of microbes, the term collectively as the microbiome, which is crucial to maintaining good health. IBD, an immune-linked inflammation disease, can result in abdominal pain, diarrhoea, and extreme fatigue.

People with IBD have a tendency to change the balance in their gut microbiome, particularly of Bacteroides and Firmicutes bacteria. However, we still cannot know how exactly this translates to the trigger and progression of IBD. By understanding how these bacteria interact with the gut lining and the immune system, and how this differs in IBD, we can better understand the causes and begin developing targeted, effective therapies.

This quest to decipher this crosstalk across the different kingdoms of existence requires that you understand how bacteria communicate and then how human cells react to that information. Dr Tamas Korcsmaros, a systems biologist, has joined the Quadram Institutes and the Quadram Institutes and partnered with Professor Simon Carding.

Bacterial Extracellular Vesicles (BEVs) are small structures created by bacteria that they fill with various molecules and release from the cell. These molecules can cross the gut lining, reaching cells of the immune system where they are recognized by receptors. The contents of the BEVs are molecular signals that then cause the immune cells to react. These signals are susceptible to cascading into widespread effects.

BEVs and their cargo are able to help with anti-inflammatory responses of the immune system, but in an inflamed IBD patients gut, this response is lost. However, we are currently unaware how they interact with the complex immune system. Using different kinds of cells is a process that involves monitoring for a wide spectrum of signals and interactions to respond appropriately to a perceived threat of infection locally and systematically across the body.

Dr Tamas Korcsmaros and his team combined a previously compiled paper into which genes are actively making proteins in 51 types of colon cells, from either healthy conditions or under the effects of ulcerative colitis. Uniquely, this dataset tented and uninflamed records from the same patients, allowing for further investigation into the effects of inflammation and not only the complex disease.

All cargo proteins obtained from BEVs from the common gut bacteria Bacteroides thetaiotaomicron (Bt) have been analysed and characterised by the researchers.

These datasets were then combined together in a microbioLink dataset (formerly called MicrobioLink), which estimates the interactions between microbial and host proteins, and how these triggers complex networks of cascading signalling systems. From this they might elucidate which organisms were capable to interact with which human proteins in the different types of immune cells, and identify the differences between these networks in a healthy gut and in IBD.

This interactionome provides a visual representation of the constant communication between gut bacteria and our own immune system. Using this knowledge, researchers can discover how organisms affect microbial proteins in healthy and inflamed conditions.

Their findings were recently published in the prestigious Journal of Extracellular Vesicles, one of the leading journals about vesicle-mediated biological communication. The research was funded by the Biotechnology and Biological Sciences Research Council, which is a part of the UK Research and Innovation (UKRI).

Many interactions were common across cell types, but the study uncovered many biological processes that were specific to one type of immune cell. Specifically focused on one path known to be beneficial in immunity and inflammation, they were able to identify differences between the same cell types in healthy and ulcerative colitis situations. Experiments using cell cultures grown together with BEVs validated the findings.

The discovery that BEVs affect the immune systems in a cell-type specific manner, and that they are altered in inflammatory bowel disease is an important step to understanding the condition, and it may, according to Lejla Gul, the first author on the paper and an iCASE PhD student at the Earlham Institute and the Quadram Institute, assist in developing BEVs as a therapeutic system. The BBSRC Norwich Research Park Biosciences Doctoral Training Partnership is backed by

In a cell-type specific resolution, interkingdom relationships with BEVs require multi-disciplinary expertise and various omics datasets. Afterward, you need a computational pipeline to analyze human data, according to Dr Tamas Korcsmaros. We hope that what we have shown here will be used by others by others to learn about our cells'' interactions and how it may be altered in other diseases.

According to Professor Simon Carding, laboratory scientists working with bioinformaticians to develop the tools and methods necessary to understand the extremely complex nature of interactions between our gut microbes and cells of our body that is crucial to maintaining our health. These insights will be invaluable in developing innovative approaches aimed at maintaining health by encouraging beneficial interactions with gut microbes and preventing harmful ones that may lead to IBD.

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