Jacques Izard

Feeding intolerance contributes to postoperative morbidity following pediatric cardiac surgery. The intestinal microbiome and milieu play a vital role in gut function. Short-chain fatty acids are gut and cardioprotective metabolites produced by commensal bacteria and help maintain appropriate barrier function. Depletion of these metabolites and barrier dysfunction contribute to postoperative feeding intolerance following cardiac surgery. Identifying mechanistic targets to improve the intestinal milieu with the goal of improved nutrition and clinical outcomes is critical.

Background: Congenital heart disease (CHD) is the most common birth defect, occurring in roughly 40,000 US births annually. Within CHD, estimates of malnutrition range from 30-42%, which can stem from feeding intolerance after cardiac surgery, and is associated with longer hospitalization and increased mortality. Cardiopulmonary bypass (CPB) is employed for the surgical repair of CHD and has been shown to induce a systemic inflammatory response syndrome (SIRS) exacerbating intestinal dysbiosis and inducing intestinal epithelial barrier dysfunction (EBD), possibly contributing to post-operative feeding intolerance (FI). Objective: To determine the relationship of post-operative FI with intestinal dysbiosis and EBD in pediatric CHD after cardiac surgery. Methods: A prospective study of patients aged 0-15 undergoing cardiac surgery with CPB. Stool and blood samples were collected both pre-operatively and post-operatively to evaluate the microbiome, EBD markers, short chain fatty acids (SCFA), and markers of inflammation. Clinical data was used to calculate a FI score and evaluate patient status post-operatively.Results: We enrolled 26 CPB patients and identified FI (n=13). Patients with FI had unique microbial shifts with reduced SCFA-producing organisms, Rothia, Clostridium innocuum, and Intestinimonas. Patients who developed FI had elevated EBD markers, claudin-2 (p<0.01), claudin-3 (p<0.001), and fatty acid binding protein (p<0.01). Patient with FI also had reduced plasma and stool SCFA levels. Conclusion: We provide novel evidence that intestinal barrier dysfunction and dysbiosis-induced SCFA depletion are associated with FI. These markers may serve as targets for mechanistic understanding and therapeutic targeting to improve nutrition and clinical outcomes following pediatric cardiac surgery.

Objective The effects of food sensitivity can easily be masked by other digestive symptoms in ostomates and are unknown. We investigated food-specific-IgG presence in ostomates relative to participants affected by other digestive diseases. Design Food-specific-IgG was evaluated for 198 participants with a panel of 109 foods. Immunocompetency status was also tested. Jejunostomates, ileostomates and colostomates were compared with individuals with digestive tract diseases with inflammatory components (periodontitis, eosinophilic esophagitis, duodenitis, ulcerative colitis, Crohn’s disease and appendicitis), as well as food malabsorption due to intolerance. A logistic regression model with covariates was used to estimate the effect of the experimental data and demographic characteristics on the likelihood of the immune response. Results Jejunostomates and ileostomates had a significant risk of presenting circulating food-specific-IgG in contrast to colostomates (OR 12.70 (p=0.002), 6.19 (p=0.011) and 2.69 (p=0.22), respectively). Crohn’s disease, eosinophilic esophagitis and food malabsorption groups also showed significantly elevated risks (OR 4.67 (p=0.048), 8.16 (p=0.016) and 18.00 (p=0.003), respectively), but not the ulcerative colitis group (OR 2.05 (p=0.36)). Individuals with profoundly or significantly reduced, and mild to moderately reduced, levels of total IgG were protected from the formation of food-specific IgG (OR 0.09 (p=Conclusion The strength of a subject’s immunocompetence plays a role in the intensity to which the humoral system responds via food-specific-IgG. An element of biogeography emerges in which the maintenance of a colonic space might influence the risk of having circulating food-specific-IgG in ostomates.

Stool descriptors have become popular due to the large diffusion of the Bristol Stool Form Scale (BSFS) via clinical studies, clinical trials, and social media. The applications have been numerous and centered around standardization of terminology that can be used by health care professionals and patients alike, as well as individuals interested in their wellness and the associated partners in the wellness industry. For a portion of the population, the digestive content is rerouted to an external manufactured pouch or bag, making the use of the BSFS visual descriptors of stool difficult. From day one post-resection surgery, ostomates are challenged with output management. The lack of standardized descriptors may hinder proper communication between the individual and the support team, as well as providing proper characterization in clinical studies and clinical trials.

A lack of prospective studies has been a major barrier for assessing the role of the microbiome in human health and disease on a population-wide scale. To address this significant knowledge gap, we have launched a large-scale collection targeting fecal and oral microbiome specimens from 20,000 women within the Nurses’ Health Study II cohort (the Microbiome Among Nurses study, or Micro-N). Leveraging the rich epidemiologic data that have been repeatedly collected from this cohort since 1989; the established biorepository of archived blood, urine, buccal cell, and tumor tissue specimens; the available genetic and biomarker data; the cohort’s ongoing follow-up; and the BIOM-Mass microbiome research platform, Micro-N furnishes unparalleled resources for future prospective studies to interrogate the interplay between host, environmental factors, and the microbiome in human health. These prospectively collected materials will provide much-needed evidence to infer causality in microbiome-associated outcomes, paving the way toward development of microbiota-targeted modulators, preventives, diagnostics and therapeutics. Here, we describe a generalizable, scalable and cost-effective platform used for stool and oral microbiome specimen and metadata collection in the Micro-N study as an example of how prospective studies of the microbiome may be carried out.

Background: In mice, bacteria from the mouth can translocate to the pancreas and impact pancreatic cancer progression. In humans, oral bacteria associated with periodontal disease have been linked to pancreatic cancer risk. It is not known if DNA bacterial profiles in the pancreas and duodenum are similar within individuals. Methods: Tissue samples were obtained from 50 subjects with pancreatic cancer or other conditions requiring foregut surgery at the Rhode Island Hospital (RIH), and from 34 organs obtained from the National Disease Research Interchange. 16S rRNA gene sequencing was performed on 189 tissue samples (pancreatic duct, duodenum, pancreas), 57 swabs (bile duct, jejunum, stomach), and 12 stool samples. Results: Pancreatic tissue samples from both sources (RIH and National Disease Research Interchange) had diverse bacterial DNA, including taxa typically identified in the oral cavity. Bacterial DNA across different sites in the pancreas and duodenum were highly subject specific in both cancer and noncancer subjects. Presence of genus Lactobacillus was significantly higher in noncancer subjects compared with cancer subjects and the relative abundance of Fusobacterium spp., previously associated with colorectal cancer, was higher in cancer subjects compared with noncancer subjects. Conclusions: Bacterial DNA profiles in the pancreas were similar to those in the duodenum tissue of the same subjects, regardless of disease state, suggesting that bacteria may be migrating from the gut into the pancreas. Whether bacteria play a causal role in human pancreatic cancer needs to be further examined. Impact: Identifying bacterial taxa that differ in cancer patients can provide new leads on etiologically relevant bacteria.