, said Chinese researchers.
The research, published recently in Pediatric Research, involved more than 80 children and showed that those with GHD had alterations in microbial populations that have been linked to longevity, as well as a microbial and metabolite signature that allowed accurate discrimination from ISS.
“These findings provide novel insights into potential early diagnosis and innovative treatment alternatives, such as fecal microbiota transplantation, for short stature with varying growth hormone levels,” the authors wrote.
Andrew Dauber, MD, MMSc, chief of endocrinology, Children’s National Hospital, Washington, who was not involved in the study, said that while this is “a really interesting area of research,” he expressed “hesitancy about getting too excited about this data yet.”
“One of the problems is how you define growth hormone deficiency,” as it is “not a black and white diagnosis,” and the etiology and child’s growth trajectory also need to be considered, Dr. Dauber told said.
He explained: “The problem is that, when you rely on the growth hormone stimulation test alone, there’s so many false positives and so much overlap between patients with true growth hormone deficiency and those without. And I think that this article fell prey to that.”
He added: “It would be really, really interesting and helpful to have a microbiome signature that allows you to distinguish between true growth hormone deficiency and patients with idiopathic short stature.”
“But you have to make sure that your groups are very well defined for this study to be really valid. And that’s one of my concerns here.”
Dr. Dauber continued: “Now, that being said, they did find some associations that correlated with growth hormone peak levels,” some which replicate previous findings, “so I do think that there are kernels of important findings here.”
‘Tease Out Influences’ to Isolate the Interaction
He pointed out that there are “many factors that influence the microbiome,” such as the use of antibiotics, diet, age, and geographic location. Therefore, a study that could truly tease out all these influences and isolate the interaction with growth hormone levels would need to be “very thoughtfully designed.”
A number of factors contribute to short stature, lead author Lan Li, MD, Department of Radiology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China, and colleagues.
These include genetic factors, environmental factors, and conditions such as being small for gestational age at birth, familial short stature, and chronic systemic diseases, as well as GHD and ISS.
Recent animal studies have suggested that there may be a bidirectional relationship between the gut microbiota and the growth hormone/insulin-like growth factor 1 axis, and it has been shown that individuals with GHD have significant alterations in their gut microbiota compared with healthy controls.
To investigate, they studied 36 children diagnosed with GHD, 32 with ISS, and 16 age- and sex-matched healthy controls, all of whom were recruited between February 2019 and June 2021 from the Pediatric Endocrinology Department of The Second Affiliated Hospital of Wenzhou Medical University.
Fecal samples obtained from the children underwent microbiome analysis using 16S ribosomal RNA gene sequencing, alongside nuclear MRI analysis of the metabolome, or the entire complement of small molecules in the samples.
Patients with GHD had a significantly higher body mass index than those with ISS (P < .05), and their peak growth hormone level was significantly lower (P < .001). Patients with GHD also had significantly higher total cholesterol and low-density lipoprotein cholesterol levels than patients with ISS (P < .05).
The team reports that the alpha diversity of the fecal microbiome, which measures the microbial diversity within a fecal sample, was similar between the three groups.
However, there was significant variation between the groups in the beta diversity, which quantifies the similarity or dissimilarity between two samples, and allows the overall taxonomic or functional diversity pattern to be linked to environmental features.
Compared with the healthy control group, the abundance of Pelomonas, Rodentibacter, and Rothia was significantly decreased in GHD and patients with ISS, while the abundance of Prevotellaceae_NK3B31_group was increased in the two patient groups, particularly in those with GHD.
In addition, the researchers found a decreased Firmicutes/Bacteroidota (F/B) ratio in participants with short stature, particularly in the GHD group. They noted that “emerging evidence suggests the F/B ratio may play a role in longevity.”
Nocardioides was substantially more common in the ISS group vs both patients with GHD and healthy controls, while Fusobacterium mortiferum was characteristic of GHD. The team suggests this “may serve as a critical intestinal factor contributing to the short stature observed in GHD.”
The metabolome analysis revealed that glucose, pyruvate, and pyrimidine metabolism may also play a significant role in distinguishing between patients with GHD and ISS and healthy control groups.
Finally, the team demonstrated that a panel combining 13 microbiome and metabolome markers was able to discriminate between GHD and ISS at an area under the receiver operating characteristic curve of 0.945, with a sensitivity of 87% and a specificity of 91%.
The study was supported by grants from the National Natural Science Foundation of China and Wenzhou Science and Technology Bureau in China. No relevant financial relationships were declared.
A version of this article appeared on Medscape.com.