Transpyloric Feed in Reflux-Associated Apnea in Preterm Newborns: A Prospective Study.

Background: The etiological correlation between gastroesophageal reflux (GER) and apnea is controversial. We conducted a prospective interventional study designed to address the controversy. Methods: Preterm neonates with apnea at a tertiary care center, who had clinical features of GER without any other comorbidities likely to cause apnea, were included in the study. The enrolled neonates underwent continuous transpyloric tube feeding for 72 hours. The primary outcome measure was the difference in the number of apneic episodes pre- and post-initiation of nasoduodenal (ND) feeding. Secondary outcome measures included the incidence of necrotizing enterocolitis, other gastrointestinal disturbances, and mortality. Results: Sixteen preterm neonates were included in the study. A substantial proportion (n =11, 68.8%) of the included neonates had a reduction in the number of apneic episodes. There was a significant decrease in the mean number of apneic episodes from 1.75 (±0.837) to 0.969 (±0.957) (P=.007). The median number of apneas was 1.5 (IQR 0.875) before and 0.5 (IQR 0.875) after ND feeds. There were no serious adverse events observed that were attributable to transpyloric feeding. Conclusion: This prospective study suggests that in a selected group of preterm neonates with reflux- associated apnea, transpyloric feeding can be an effective therapeutic modality.

Host-microbiota interactions shaping T-cell response and tolerance in type 1 diabetes.

Type-1 Diabetes (T1D) is a complex polygenic autoimmune disorder involving T-cell driven beta-cell destruction leading to hyperglycemia. There is no cure for T1D and patients rely on exogenous insulin administration for disease management. T1D is associated with specific disease susceptible alleles. However, the predisposition to disease development is not solely predicted by them. This is best exemplified by the observation that a monozygotic twin has just a 35% chance of developing T1D after their twin's diagnosis. This makes a strong case for environmental triggers playing an important role in T1D incidence. Multiple studies indicate that commensal gut microbiota and environmental factors that alter their composition might exacerbate or protect against T1D onset. In this review, we discuss recent literature highlighting microbial species associated with T1D. We explore mechanistic studies which propose how some of these microbial species can modulate adaptive immune responses in T1D, with an emphasis on T-cell responses. We cover topics ranging from gut-thymus and gut-pancreas communication, microbial regulation of peripheral tolerance, to molecular mimicry of islet antigens by microbial peptides. In light of the accumulating evidence on commensal influences in neonatal thymocyte development, we also speculate on the link between molecular mimicry and thymic selection in the context of T1D pathogenesis. Finally, we explore how these observations could inform future therapeutic approaches in this disease.

Thymic development of gut-microbiota-specific T cells.

Humans and their microbiota have coevolved a mutually beneficial relationship in which the human host provides a hospitable environment for the microorganisms and the microbiota provides many advantages for the host, including nutritional benefits and protection from pathogen infection1. Maintaining this relationship requires a careful immune balance to contain commensal microorganisms within the lumen while limiting inflammatory anti-commensal responses1,2. Antigen-specific recognition of intestinal microorganisms by T cells has previously been described3,4. Although the local environment shapes the differentiation of effector cells3-5 it is unclear how microbiota-specific T cells are educated in the thymus. Here we show that intestinal colonization in early life leads to the trafficking of microbial antigens from the intestine to the thymus by intestinal dendritic cells, which then induce the expansion of microbiota-specific T cells. Once in the periphery, microbiota-specific T cells have pathogenic potential or can protect against related pathogens. In this way, the developing microbiota shapes and expands the thymic and peripheral T cell repertoire, allowing for enhanced recognition of intestinal microorganisms and pathogens.