IBD Severity in Children Can Be Predicted by Genetic Testing

The good news for children suffering from IBD and their parents is that a group of Norwegian research scientists has had a recent breakthrough in determining a new test to both diagnose and categorize IBD through the profiling of the bacterial composition of the large bowel.

Inflammatory bowel disease (IBD) is a chronic, often relapsing, disease in which the patient experiences inflammation in the gastrointestinal (GI) tract. Physicians often have a difficult time diagnosing IBD because there are many symptomatic complaints that can mimic IBD.

Irritable bowel syndrome (IBS) is one of the noninflammatory disorders that often have very similar symptoms as IBD. Furthermore, the threshold for performing invasive procedures, such as upper endoscopy and colonoscopy is high in children. IBD is usually more aggressive in children than it is in adults and can have much more dire consequences. IBD can often affect the social, psychological, and physical development of young children and adolescents.

Therefore, it is imperative that treatment of IBD be carried out as early as possible so as to reduce the negative effect that inflammation can have. One of the biggest problems with IBD remains its difficulty in diagnosis. There are a number of markers that are required to identify children with IBD who are at the greatest risk of developing a complicated course of the disease and those markers are imperative to determine the most appropriate course of action and treatment.

Predictability in children

Researchers continue to try to understand why IBD is usually more aggressive in children than it is in adults as well as why the disease course is often so difficult to predict.

Childhood cases of IBD usually start around the age of 12 or 13. IBD can interfere with this sensitive developmental stage as children begin to go into puberty and experience growth spurts (mentally, socially, and physically).

IBD can cause children at this crucial age group to experience delays in puberty, mild to severe loss of weight, growth delays, and the social and psychological effects of having to miss out on social activities and school. The effects seem to be equally detrimental in children with Crohn's disease as it is in ulcerative colitis.

Thus far, about half of Crohn's disease patients need aggressive treatment of a biologic therapy like infliximab within 6 months or so in order to go into remission. Biologic therapies are generally extremely potent and expensive and are usually only recommended after simpler and cheaper medications have been tried with no positive effects.

Risk factors

There are a number of risk factors that can determine how serious and complicate a disease course may be. Some of those risk factors include the development of a stenosis in the bowel, having fistulas, having deep ulcerations in the wall of the bowel, experiencing a widely spread disease distribution (as is common in child patients), and being of young age (under 40 years old and including children).

Diagnosis in children

Time is crucial in diagnosing children with IBD in order to formulate and administer the best course of action for healing the bowel, inducing remission, and preventing restricted growth. Time is also of the essence in order to avoid and complications and delays in puberty. The health community and patients would benefit from improved methods of determining which children and adolescents qualify for early and aggressive treatment options.

A new test

A new test has been developed that can help predict the severity of disease course in children with IBD. The test, which is called the GA (Genetic Analysis) Dysbiosis Test, was developed in Oslo, Norway and uses and advance profiling method of DNA from feces in order to detect certain bacteria in the large bowel. To date, there are currently 54 different bacterial probes that are based on the bacteria's genetic profile (16S rRNA sequence) and measure the relative number of bacteria which is calculated using fluorescent signals that vary in strength depending on the number of bacteria.

This new technology can cover up to 300 different species of bacteria and the results are presented in the form of relative abundances of bacteria which can be measured as "fluorescence signal strength".

The company that created this technology has also created an Index that can compare and analyze the data from a patient with the data from a healthy adult population. This Index is called the Dysbiosis Index (DI). According to the DI, the value of the DI is considered to be higher when the microbiota from the patient data is more differentiated than the healthy population is.

The researchers characterized the intestinal microbiota by recording the fluorescence signal strength (FSS) from 54 individual probes. The researcher continued their study by also choosing the 6 probes that had significantly lower FSS in patients with IBD compared with patients who did not have IBD.

IBD patients with lower values than the values of healthy children were given 1 point for each time their value was lower. The researchers then developed an Index that ranged the resulting points from 0 to 6 with 6 meaning that all 6 of the probes were different in children with IBD than in children without IBD. The researchers were then able to create a statistical model that showed the estimated odds for having IBD based on the scores in the Index.

Although the GA-map Dysbiosis Test had previously not been used to test children with IBD younger than 18 years old, the current research studied the fecal samples of various children between ages 2 and 18 years old. In total, the researchers tested the fecal samples of 235 children and adolescents. The population was broken down as follows: 75 children were healthy, 50 children did not have IBD but did have gastrointestinal symptoms, 27 children had ulcerative colitis, 80 children had Crohn's disease, and 3 children had unclassified forms of IBD.

The researchers used the GA-map Dysbiosis Test to analyze the fecal matters and to create microbiota profiles which they then compared between a group of healthy children, 50 children who had gastrointestinal symptoms without an IBD diagnosis, and 110 children who had just recently been diagnosed with IBD.

Results of the research

The researchers found very distinct difference in the profiles that they compared between the healthy comparison group, the symptomatic patients without IBD, and the patients with IBD. Specifically, they found that the fluorescence signal strength was much higher in the healthy group, lower in the group with IBD, and ever lower in the group with symptoms but no IBD.

Furthermore, the researchers found that the children who had microbiota profiles with the highest level of disturbance were also the children who had the worst symptoms and activity levels in their IBD. Those children were also at the greatest risk of requiring the treatment of TNF blockers sometime in the future. The results also indicated that the patients who had the least number of bacteria, like Bifidobacterium, Clostridia, and Proteobacteria were also the patients who had the most extensive cases of IBD.

Children who managed their symptoms with conventional medications had a higher abundance of Actinobacteria as well as a higher abundance of Bacteroidetes, Tenericutes, and Firmicutes than children had prior to treatment.

Final thoughts

Although this recent study supports the idea that IBD and microbiota are linked, little is known as to which comes first: the IBD or the microbiota. There needs to be more research done on just what role the microbiota plays in the development and course of the disease.

Reference

Olbjourn, C. (2017, July 26). Genetic Test to Predict IBD Severity in Children. [Web]. In News Medical Life Sciences. Retrieved from: https://www.news-medical.net/news/20170726/Genetic-test-to-predict-IBD-severity-in-children.aspx