Predicting celiac disease via the infant’s microbiota

Vignette

Celiac disease is an autoimmune disease triggered in response to ingestion of gluten. A Spanish team has attempted to find elements in the intestinal microbiota of newborns, which could allow development of the disease to be predicted beyond the existence of a genetic predisposition.

 

The genetic nature of celiac disease is now well known: subjects at risk carry HLA-DQ2/HLA-DQ8 allelic variants and represent 30 to 40% of the Caucasian population. However, only 1 to 3% of these individuals will develop the condition, and the risk increases to 10% when a first degree relative is affected, suggesting that other factors are involved in triggering the disease. Observational studies have demonstrated intestinal dysbioses in sufferers, without however giving a precise description of their role in the etiology of the disease. For the first time, researchers have investigated the development of the microbiota in the first months of life in subjects with a family history of the condition and prior to development of the disease. The study included healthy newborns (10 patients/10 control subjects) with at least one close family member affected, and who were fed gluten from the age of 6 months. Antibiotic intake and dietary habits such as breastfeeding were monitored for five years.

Protective microbial diversification

Study of the microbiota revealed interesting information regarding the development of the intestinal flora: between the age of four and six months, the microbiota of the healthy children showed a gradual increase in bacterial diversity, while children who would go on to develop celiac disease had greater diversity at baseline, suggesting premature maturation of the microbiota. This gradual increase in bacterial diversity, not found in the sick children, is thought to be characteristic of a progression towards a healthy microbiota and which could allow disease resilience. The authors moreover confirm that the risk of developing the disease was associated with a decrease in the Bifidobacterium genus, particularly B. longum, which could potentially be a predictive biomarker. In fact, an increase in the relative abundance of B. longum was associated with the control group.

Reduced sIgA levels in people affected by celiac disease

The other aspect of the study dealt with the immunological markers which precede the disease. A significant reduction in secretory IgA (sIgA) between the age of four and six months was observed exclusively in the sick children. sIgA is the first line of defense of the intestine, interacting with antigens and microbes, and contributes to intestinal immunological homeostasis, by preventing bacterial penetration through tissues, as well as mediating immune tolerance to flora. According to the authors, a premature reduction in sIgA might therefore increase the risk of developing an autoimmune disease. It should be noted that the TNF-α levels in the healthy children were higher than in the patient group. Moreover, this increase was was correlated with the presence of Bifidobacterium  spp. The authors consider that the increase in this inflammatory cytokine could reflect a healthy maturation of the intestinal microbiota and an increase in its diversity. On the other hand, a premature increase in IL-6 was observed in the children who ended up developing the disease, which is thought to be synonymous with premature and detrimental maturation of the microbiota. The intestinal microbiota is thought to influence gluten tolerance through development of the immune system, as proven by some non-clinical studies. Studies in larger populations are however necessary to confirm this hypothesis, and perhaps to provide key elements for the primary prevention of celiac disease.

 

Sources:

M. Olivares et al. Gut microbiota trajectory in early life may predict development of celiac disease. Microbiome, vol. 6, févr. 2018.