Reclassification of asymptomatic beta cell autoimmunity : a critical perspective

Type 1 diabetes is an immune-mediated disease leading to almost total beta cell destruction and permanent exogenous insulin dependency. The appearance of clinical symptoms is preceded by an asymptomatic preclinical period, the duration of which is highly individual. The emergence of diabetes-associated autoantibodies into the peripheral circulation is the first detectable sign of beta cell autoimmunity. If type 1 diabetes is diagnosed in childhood the preclinical period lasts for an average of 2.5-3 years, but clinical symptoms may in some cases appear within a few months or be delayed for more than 20 years. In this issue of Diabetologia, Bonifacio and colleagues (doi:) suggest that asymptomatic beta cell autoimmunity should be considered as a pathological and diagnostic entity. Although such a strategy may have some positive consequences, it might also have serious drawbacks. To label an asymptomatic child that may have 10-20 years of a healthy life ahead of him/her as a patient will most likely affect both the life of the family and the child. Therefore, we think that one should not adapt the new diagnosis before the psychological consequences of such a strategy have been assessed. Instead, since metabolic abnormalities precede the appearance of clinical symptoms of type 1 diabetes, analysis of a combination of immunological and metabolic markers will provide better insight into the likelihood of progression to clinical disease, with a shorter 'sickness' period.Peer reviewe

Effect of Early Feeding on Intestinal Permeability and Inflammation Markers in Infants with Genetic Susceptibility to Type 1 Diabetes : A Randomized Clinical Trial

Objectives To assess whether weaning to an extensively hydrolyzed formula (EHF) decreases gut permeability and/or markers of intestinal inflammation in infants with HLA-conferred diabetes susceptibility, when compared with conventional formula. Study design By analyzing 1468 expecting biological parent pairs for HLA-conferred susceptibility for type 1 diabetes, 465 couples (32 %) potentially eligible for the study were identified. After further parental consent, 332 babies to be born were randomized at 35th gestational week. HLA genotyping was performed at birth in 309 infants. Out of 87 eligible children, 73 infants participated in the intervention study: 33 in the EHF group and 40 in the control group. Clinical visits took place at 3, 6, 9, and 12 months of age. The infants were provided either EHF or conventional formula whenever breastfeeding was not available or additional feeding was required over the first 9 months of life. The main outcome was the lactulose to mannitol ratio (L/M ratio) at 9months. The secondary outcomes were L/M ratio at 3, 6, and 12 months of age, and fecal calprotectin and human beta-defensin 2 (HBD-2) levels at each visit. Results Compared with controls, the median L/M ratio was lower in the EHF group at 9 months (.006 vs.028; P = .005). Otherwise, the levels of intestinal permeability, fecal calprotectin, and HBD-2 were comparable between the two groups, although slight differences in the age-related dynamics of these markers were observed. Conclusions It is possible to decrease intestinal permeability in infancy through weaning to an extensively hydrolyzed formula. This may reduce the early exposure to dietary antigens.Peer reviewe

Strain-Level Analysis of Mother-to-Child Bacterial Transmission during the First Few Months of Life

Bacterial community acquisition in the infant gut impacts immune education and disease susceptibility. We compared bacterial strains across and within families in a prospective birth cohort of 44 infants and their mothers, sampled longitudinally in the first months of each child’s life. We identified mother-to-child bacterial transmission events and describe the incidence of family-specific antibiotic resistance genes. We observed two inheritance patterns across multiple species, where often the mother’s dominant strain is transmitted to the child, but occasionally her secondary strains colonize the infant gut. In families where the secondary strain of B. uniformis was inherited, a starch utilization gene cluster that was absent in the mother’s dominant strain was identified in the child, suggesting the selective advantage of a mother’s secondary strain in the infant gut. Our findings reveal mother-to-child bacterial transmission events at high resolution and give insights into early colonization of the infant gut

Strain-Level Analysis of Mother-to-Child Bacterial Transmission during the First Few Months of Life

Bacterial community acquisition in the infant gut impacts immune education and disease susceptibility. We compared bacterial strains across and within families in a prospective birth cohort of 44 infants and their mothers, sampled longitudinally in the first months of each child's life. We identified mother-to-child bacterial transmission events and describe the incidence of family-specific antibiotic resistance genes. We observed two inheritance patterns across multiple species, where often the mother's dominant strain is transmitted to the child, but occasionally her secondary strains colonize the infant gut. In families where the secondary strain of B. uniformis was inherited, a starch utilization gene cluster that was absent in the mother's dominant strain was identified in the child, suggesting the selective advantage of a mother's secondary strain in the infant gut. Our findings reveal mother-to-child bacterial transmission events at high resolution and give insights into early colonization of the infant gut. Using longitudinal metagenomic sequencing from 44 mother/child pairs, Yassour et al. characterized mother-to-child strain transmission patterns. While mothers' dominant strains were often inherited, nondominant secondary strain transmissions were also observed. Microbial functional analysis reveals that inherited maternal secondary strains may have a selective advantage to colonize infant guts.National Institutes of Health (Grant 1DP3DK094338–01