Infant microbiome dysregulation predicts juvenile idiopathic arthritis development
Click Here to Manage Email Alerts
Key takeaways:
- Microbiome markers during infancy may predict the development of JIA.
- Breastfeeding length and antibiotic exposure may also correlate to JIA risk.
Infants who demonstrate microbiome dysregulation may be at a higher risk for juvenile idiopathic arthritis, according to data published in eBioMedicine.
“JIA risk increases in a dose-dependent manner with antibiotic exposure before 2 years of age, even after adjustment for infections,” Erik Kindgren, MD, of Skaraborg Hospital, in Skövde, Sweden, and colleagues wrote. “Evidence suggests that the greater the disruption by antibiotics, the greater the risk for JIA. The effect is stronger for antibiotics targeting anaerobes, likely due to longer impacts on the microbiota. Diet can also increase risk.
“These and other environmental factors influence the microbiome, which affects metabolic and immunological homeostasis, maintains the integrity of the intestinal mucosa, and trains the immune system,” they added. “Even a short-term effect on the newborn’s intestinal microbiome can have long-term effects due to the early maturation of the immune system. ... There are no extant studies of the gut microbiota in children in the years preceding a diagnosis. Here, a novel question is explored. Does the gut microbiome differ in those with future JIA disease as early as in infancy?”
To investigate the impact of gut microbiota on the potential development of JIA, Kindgren and colleagues analyzed data from the All Babies in Southern Sweden population cohort, which includes children born between Oct. 1, 1997, and Oct. 1, 1999, in southern Sweden. Parents of children in the cohort completed surveys at birth and other intervals, providing information on antibiotic and drug use, as well as nutrition and infection histories. Diagnostic data were obtained for any patient diagnosed with JIA before December 2020.
At 1 year, fecal samples of patients were collected and stored at –80 degrees Celsius. Samples were randomized, and researchers added “blank negative” to protect against contamination, they wrote. Patients’ environment and microbiome, as well as the number of antibiotic treatments received and the total months spent breastfeeding, were assessed.
A total of 17,055 patients were included in the cohort. Among these children, 111 ultimately developed JIA. In general, patients who developed JIA demonstrated a higher concentration of microbiota, including Acidaminococcales, Prevotella 9, and Veillonella parvula, according to the researchers. These patients also had lower rates of Coprococcus, Subdoligranulum, Phascolarctobacterium, Dialister spp., Bifidobacterium breve, Fusicatenibacter saccharivorans, Roseburia intestinalis and Akkermansia muciniphila.
One particular aspect of the microbiome that correlated strongly with later development of JIA was Parabacteroides distasonis (OR = 6.7; 95% CI, 1.81-24.84), according to the researchers. Correlation with JIA increased in patients with reduced breastfeeding length or increased antibiotic treatments.
“This is the first investigation to demonstrate that early-life microbiome markers for JIA risk exist prior to disease onset, and furthermore, to provide evidence that they could be harnessed as early as one year of age,” Kindgren and colleagues wrote. “Risk factors may be mediated by heredity-environment interactions, as our work demonstrates increased cumulative risk specifically in genetically vulnerable individuals.”
Perspective
Back to Top
There have been multiple studies conducted evaluating the connection between the gut microbiome and patients with juvenile idiopathic arthritis. Previous studies have also identified differences in the gut microbiome, lending to some possible understanding to the pathogenesis of the disease. However, these other studies have evaluated the microbiome of patients with JIA after diagnosis and treatment initiation. This study is the first to evaluate the microbiome prior to diagnosis and, of course, treatment.
The study used a birth cohort to evaluate if the gut microbiome was different in the infant who later developed JIA. Although it is noted that this was a small patient sample size for this cohort study, future studies such as this could provide valuable information in identifying children who could be at risk for developing JIA.
To allow for the possibility of disease prevention, further studies are needed to demonstrate an early connection between the gut microbiome and JIA, as well as a clear understanding of the role the microbiome in the pathogenesis of JIA.
Collapse
Read more about
Click Here to Manage Email Alerts