Infants at Risk of Type 1 Diabetes Benefit from Early Probiotics

Becky McCall

November 10, 2015

Exposure to probiotics during the first month of life is associated with a 60% decrease in the risk of pancreatic beta-cell islet autoimmunity among children with type 1 diabetes–associated HLA genotype DR3/4, but not among those with other genotypes.

The results are published online November 9 in JAMA Pediatrics, after a preliminary presentation at the European Association for the Study of Diabetes (EASD) in 2014, as reported by Medscape Medical News.

The authors, led by Ulla Uusitalo, PhD, a nutritionist at the University of South Florida, Tampa, note, "This is the first time, to our knowledge, that the association between probiotic use and type 1 diabetes–related islet autoimmunity has been studied in a longitudinal, observational setting among genetically high-risk children."

The observed reduction in risk of pancreatic beta-cell islet autoimmunity was seen only in those children who had received dietary supplements of probiotics or fortified formula milk during the first 27 days of life, compared with those who received supplementation after 27 days or no supplementation at all (hazard ratio [HR], 0.66).

This association was mainly accounted for by children with the specific HLA genotype DR3/4, for whom the hazard ratio was 0.40 for the same comparison. Children with other genotypes demonstrated no association between probiotic use in the first month of life and islet autoimmunity (HR, 0.97 compared with those with later or no exposure to probiotics).

"This is a very strong association, but we need to study this further to understand it better," Dr Uusitalo pointed out.

The researchers also found that probiotic supplementation was most prevalent in Finland (used in 52.4% of study population there) and Germany (46.8% of infants) during the first year of life. In the United States, only 6.1% of study infants received probiotics during this period.

Ability to Protect Against Type 1 with Probiotics "Striking"

In an editorial accompanying the paper, George M Weinstock, PhD, of the Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, writes: "The ability to protect against type 1 diabetes mellitus in individuals with genetic risk by the introduction of bacteria into the gut is indeed striking.

"Genetic disease need not carry the burden of inevitability," he adds, pointing out that "the ability to treat these diseases by introduction of bacteria would be a new paradigm.

"While probiotic use in children is not that common in the United States, statistics in the current study show it to be more widespread in the study's other participating sites of Finland, Germany, and Sweden. This is an area in its infancy but likely to have a large impact on the medicine of the future," he added.

TEDDY Study: Trying to Identify Environmental Causes of Type 1 Diabetes

The analysis is part of the ongoing, prospective Environmental Determinants of Diabetes in the Young (TEDDY) study, started in 2004 and including children from six clinical centers: three in the United States (Colorado, Georgia/Florida, and Washington) and three in Europe (Finland, Germany, and Sweden).

The primary goal of TEDDY is to try to identify environmental causes of type 1 diabetes.

A final sample consisting of 7473 children with an age range of 4 to 10 years (as of October 31, 2014) were included in the current analysis. Children were followed up for type 1 diabetes–related autoantibodies using blood samples that were collected every 3 months between 3 and 48 months of age, and every 6 months thereafter to determine persistent islet autoimmunity.

Probiotics containing mainly Lactobacillus and Bifidobacterium were given either as a supplement or in probiotic-fortified infant formula. Data on infant feeding, including probiotic supplementation and infant-formula use, were monitored from birth using questionnaires and diaries.

The primary outcome of this analysis was the development of persistent confirmed islet autoimmunity (confirmed positive antibodies to insulin, glutamic acid decarboxylase, or insulinoma antigen 2).

Time-to-event analysis was used to study the association between probiotic use and islet autoimmunity. Results were stratified by country and adjusted for family history of type 1 diabetes, HLA DR/DQ genotypes, sex, birth order, mode of delivery, exclusive breastfeeding, birth year, child's antibiotic use, and diarrheal history, as well as maternal age, probiotic use, and smoking.

Predictors of probiotic use during the first year of life were: older maternal age, being a first-born child (P < .001), probiotic use during pregnancy (P < .001), not smoking during pregnancy (P = .006), later birth year(P < .001), shorter exclusive breastfeeding (P = .003), antibiotic use by the child (P < .001), or having diarrhea (< .001) or gastroenteritis (P < .001).

Probiotic Effect on Gut Microbiome in First Month of Life

In his editorial, Dr Weinstock notes that "it is likely that the effect of probiotic exposure is through the microbiome and that influencing the gut microbiota with ingested probiotics might be more effective very early in life, before a robust microbiome is established."

He added that the "striking difference in probiotic protection between children with the DR3/4 genotype and all other genotypes suggests a host effect such as an interaction of the immune system with the introduced and/or resident bacteria."

This work also raises the question of whether there are better bacterial strains for the prevention of type 1 diabetes than used here and whether the current general-purpose organisms could be of benefit for other diseases, which in turn could have their own optimally protective organisms.

"And what would it take for this type of treatment to be widely accepted into medical practice? Microbial treatments, whether preventive with probiotics or therapeutic as with fecal microbiota transplant, are attracting more interest," he observes.

In conclusion, Dr Uusitalo emphasized that "no recommendations on probiotic use can be made based on one study only. One of the next steps is to study the association between probiotic use and gut microbiome."

The study authors and Dr Weinstock have declared no relevant financial relationships.

JAMA Pediatr. Published online November 9, 2015. Article, Editorial


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