An interesting translational symposium of the American Association of Gastroenterology (AGA) at this year’s Digestive Disease Week (DDW) in Washington, D.C., was entitled, “Gut Microbiome and Clinical Outcomes in Pediatrics”.
Speakers in this session discussed the current evidence on how the gut microbiome is established at birth and influenced by host and environmental factors. They also presented evidence on the role of the gut microbiome in the pathogenesis of obesity, food allergies, and IBD, and they reviewed potential treatment and preventive interventions by manipulating the gut microbiome.
Gut microbiota of premature infants
Phillip Tarr, M.D., from Washington University School of Medicine in St. Louis shared insights on how the gut microbiome is established by studying the gut flora in premature infants in the tightly controlled microbial environment of a neonatal intensive care unit (NICU). In general, the gut microbiota progresses through a choreographed succession of bacterial classes from Bacilli to Gammaproteobacteria to Clostridia. Antibiotics, vaginal vs. caesarian birth, diet, and age of the infants when sampled influence the pace, but not the sequence, of this patterned progression. The pace of this progression is most strongly influenced by gestational age, with the microbial population assembling slowest for infants born most prematurely. In conclusion, Tarr suggested that these data might point towards a predominant influence of host biology (gestational age at birth) over exogenous factors on the development and establishment of bacterial populations in the premature newborn infant gut.
Obesity and the microbiota
In the second talk of this session, Lee Kaplan, M.D., Ph.D., from Harvard focused on microbiome and obesity and presented an alternative model of the mechanism of microbiota regulation of body fat. He emphasized that there is an interplay between microbiota and body function, that the microbiota is not a solo player and that the effects of the microbiota may not be physical but rather occur through signaling (at least with respect to metabolic function). Despite new insights into the complex relationship between microbiome and obesity, several essential questions remain to be answered:for example, how the microbiota affects energy intake and harvest and what signals play a role.
Mechanisms of autoimmune dysfunction
Richard Blumberg, M.D., from Brigham and Women’s hospital in Boston, pointed out the rapidly increasing incidence of autoimmune disorders over the last 50 years, while infection rates were decreasing at the same time. In his talk, he focused on the connection between the microbiome and food allergy. He made a parallel with the role of CD1d and natural killer T (NKT) cells in the pathogenesis of inflammatory bowel disease (IBD), a condition in which the homeostasis at mucosal surfaces is perturbed. NKT cells are a subgroup of T cells, which recognize self and microbial lipid antigens that are presented by a key mediator of host-microbial interactions, named CD1d. Blumberg hypothesizes that a perturbation of the bidirectional cross-talk between the microbiota and CD1d-restricted NKT cells could contribute to the pathogenesis of immune-mediated disorders at mucosal surfaces.
Engraftment in fecal microbiota transplantation
Eric Alm, Ph.D., from MIT spoke briefly on the microbiome and IBD and reported about efforts to engineer the microbiome to cure Clostridium difficile infections through fecal microbiota transplantation (FMT). These studies also resulted in a clinical trial. He expressed a specific interest in elucidating the factors that determine engraftment of the fecal transplant, i.e. phylogeny or species-species interaction. His lab developed software to analyze metagenomics reads in order to identify genotype and abundance of the microbiota. His group found that Operational Taxonomic Units (OTUs) rarely engraft, but that strains travel together when they do. Alm wants to fine-tune the preparation of the FMT, wants to find out if there is competitive exclusion, and wants to discover whether certain OTUs are excluded by the host during the process of FMT.