Gut Bacterial Markers May Aid Diagnosis of Children
Analysis of five bacterial markers present in the gut microbiome — the community of microbes living in the gut — may help in diagnosing myasthenia gravis (MG) in children, according to a Chinese study.
The study, “Metagenome-wide association study of gut microbiome revealed potential microbial marker set for diagnosis of pediatric myasthenia gravis,” was published in the journal BMC Medicine.
MG occurs when the immune system mistakenly attacks the neuromuscular junction, which is the place where neurons and muscle cells connect and communicate.
In Europe and North America, the majority of patients are adults, but estimates indicate that 10–15% of MG cases arise in children. In China, the proportion of children with MG can reach up to 50%, with the first disease manifestations taking place before age 15.
Pediatric MG is more challenging to diagnose, since most children do not respond well to conventional diagnostic tests, such as fatigue and repetitive nerve stimulation tests.
Increasing evidence suggests that the human gut microbiome plays a key role
in determining susceptibility to certain diseases, including MG, as well as responses to therapy.
Previous research has suggested that the gut microbiome of adults with MG might be less diverse and more pro-inflammatory than that of healthy people. However, whether this also holds true in children is still unclear.
In this study, a team of researchers compared the gut microbiome of 53 MG pediatric patients (mean age 6.64 years) and 46 age- and gender-matched healthy controls (mean age 7.51) who were recruited at a hospital in China.
Fecal samples from study participants were collected and used as a source of microbial DNA investigators then used to examine and compare their gut microbiome profile.
Results showed that the gut microbiome differed between children with MG and healthy controls. Specifically, the analysis revealed that 16 different species of bacteria were enriched in the gut microbiome of children with MG, while only nine bacteria species were found to be enriched in the microbiome of healthy controls.
Next, researchers assessed whether gut microbiome profiling could help distinguish children with MG from those without the disease. To that end, they developed a disease classification system using data from the 25 bacteria species they had found to be enriched in the gut microbiome of children with and without MG in their first analysis, and tested it in an independent group of 19 MG patients.
In the end, five bacteria species were selected as potential microbial markers, including Fusobacterium mortiferum, Prevotella stercorea, Prevotella copri, Megamonas funiformis, and Megamonas hypermegale.
Results obtained from both the original group and the independent group confirmed that all five bacteria species were enriched in MG patients
Most importantly, investigators found this set of five microbial markers could be used to differentiate children with and without MG, as shown by the Area Under the Curve (AUC) performance test. This test typically is used to measure the accuracy of a given diagnostic test. Its values range from zero to 1, with higher values reflecting a test’s higher accuracy at distinguishing patients with a disease from those without it.
In this type of analysis, AUC reached a value of 0.94 in the initial group, and of 0.84 in the independent group.
“This validation demonstrated that gut microbial features could be used to distinguish MG patients from HC [healthy controls],” the researchers wrote.
Microbiome analysis also revealed the presence of a human adenovirus in the stool of 10 MG patients, which was not detected in healthy participants.
Investigators also examined and compared the microbiome of MG children who were positive (34 children) and negative (19 children) for acetylcholine receptor (AChR) antibodies — the most common self-reactive antibodies found in MG patients. They found that Prevotella stercorea was the only bacteria species significantly enriched in the group of children lacking AChR antibodies.
Finally, researchers looked at the levels of short-chain fatty acids, or SCFAs, which are metabolites produced by microbes and known for their beneficial properties for the gut.
Results revealed that blood SCFA levels were lower in MG children from the first group. In particular, butyric acid and isobutyric acid were reduced significantly in the blood of children with MG compared with healthy controls.
Moreover, they found SCFA levels were correlated with the abundance of different gut bacteria. Lactobacillus sanfranciscensis and Prevotella nanceiensis were positively correlated with the levels of butyric acid, while Bacteroides dorei, Erysipelotrichaceae bacterium 3_1_53, and Eubacteriaceae bacterium ACC19a were positively correlated with the levels of isobutyric acid.
Notably, from all these bacteria species, Erysipelotrichaceae bacterium 3_1_53 was the only that was found to be enriched in MG patients. All others were found to be enriched in healthy controls.
Overall, these findings indicate that “altered fecal microbiota might play vital roles in pediatric MG’s pathogenesis [disease development] by reducing SCFAs,” the researchers wrote.
Investigators also noted these “novel microbiota-targeted markers will significantly help for the diagnosis of pediatric MG.”