Fecal Microbiomes in Premature Infants With and Without Parenteral Nutrition-Associated Cholestasis.

INTRODUCTION: Premature infants often require parenteral nutrition (PN) until they reach enteral autonomy which puts them at risk of developing PN-associated cholestasis (PNAC). We sought to compare longitudinal changes in fecal microbiomes of premature infants who developed PNAC versus those who did not despite being on similar PN doses. METHODS: Stool samples from premature infants (gestational age <30 weeks) who developed direct bilirubin ≥1.5 mg/dL while receiving PN were classified as precholestasis, cholestasis, or postcholestasis based on bilirubin levels at the time of sample acquisition and were compared to matched control groups 1, 2, and 3, respectively. RESULTS: A total of 102 fecal samples from 8 cases and 10 controls were analyzed. Precholestasis samples were more abundant in phylum Firmicutes and genus Staphylococcus, whereas control 1 was more abundant in phylum Proteobacteria and genus Escherichia-Shigella. Nonmetric multidimensional scaling ordination plots based on the taxonomic composition of early fecal samples revealed significant separation between cases and controls. On indicator species analysis, genus Bacilli was more prevalent in samples from the precholestasis group, whereas genus Escherichia-Shigella was more prevalent in control 1. With feeding advances, weaning of PN and resolution of PNAC, most differences in microbiota resolved with the exception of control 3 group being more diverse compared to the postcholestasis group. CONCLUSIONS: Premature neonates who develop PNAC, compared to those who do not, show significantly different fecal microbiomes preceding the biochemical detection of cholestasis.

Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection and Other Conditions in Children: A Joint Position Paper From the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

Fecal microbiota transplantation (FMT) is becoming part of the treatment algorithms against recurrent Clostridium difficile infection (rCDI) both in adult and pediatric gastroenterology practice. With our increasing recognition of the critical role the microbiome plays in human health and disease, FMT is also being considered as a potential therapy for other disorders, including inflammatory bowel disease (Crohn disease, ulcerative colitis), graft versus host disease, neuropsychiatric diseases, and metabolic syndrome. Controlled trials with FMT for rCDI have not been performed in children, and numerous clinical and regulatory considerations have to be considered when using this untraditional therapy. This report is intended to provide guidance for FMT in the treatment of rCDI in pediatric patients.

Fecal transplantation: re-discovering the value of stool.

PURPOSE OF REVIEW: For over 1000 years, stool in various forms has been used to treat disease. Within the past few decades, fecal infusion either rectally or via a nasogastric tube has become a viable option for the treatment of refractory Clostridium difficile infection (CDI), and, more recently, it has shown promise in treating inflammatory bowel disease (IBD) and metabolic disease. The purpose of this article is to review the use of feces as a treatment option in pediatric disease. RECENT FINDINGS: The majority of publications detailing the use of fecal infusion as a medical treatment have been case reports. In the first randomized controlled trial of its kind, fecal infusion via nasogastric tube was shown to be beneficial in treating refractory CDI in adults. In another first of its kind, a pilot study on the use of fecal enemas to treat ulcerative colitis in pediatric patients found it to be well tolerated and effective. SUMMARY: The infusion of feces into the intestinal tract shows great promise for treatment and modulation of a variety of intestinal and extraintestinal diseases. Defining the underlying mechanism, microbes, and metabolites that mediate this effect will lead to more directed, safer, and potentially more effective treatments.

Improved Delivery of Fat From Human Breast Milk via Continuous Tube Feeding.

BACKGROUND: Human breast milk is used sparingly in infants with intestinal failure due to observations from studies using syringe pumps that show loss of macronutrients with continuous feeding. Because of the potential benefits of using human milk, we sought to assess macronutrient losses using human milk as continuous tube feeds as done in the inpatient and home setting using a feeding bag and pump. METHODS: Using in vitro simulations of human milk to assess macronutrient losses with continuous tube feeds, hourly samples were analyzed using the SpectraStar Near-Infrared Analyzer (Unity Scientific, Columbia, MD). Effects of agitation and positional changes of the feeding bag on macronutrient delivery were investigated in 249 total samples. Pairwise comparisons were performed using repeated-measures analysis of variance. RESULTS: Significant fat losses were observed at all rates at hours 1-4, averaging to 73% at 5 mL/h. Caloric losses correlated strongly with fat losses. Significant gains in the fat content (+116% at hour 4 at 5 mL/h) were seen in the preinfusion aliquots (feeding bags). Horizontal positioning and continuous agitation of the feeding bag only partially limited fat losses. Fat delivery at 5 mL/h was significantly enhanced to 87% when the feeding bag was placed in an inverted position and improved further up to 98% with higher infusion rates. No carbohydrates and proteins losses were seen. CONCLUSIONS: Enabling the delivery of the human milk from the top of the feeding bag optimizes fat delivery and limits losses. Such top infusing feeding bags should be developed and could decrease healthcare costs for intestinal rehabilitation programs.

Transition to a Tube Feeding Formula With Real Food Ingredients in Pediatric Patients With Intestinal Failure.

Due to concerns related primarily to allergic response and malabsorption, enteral nutrition therapy has traditionally relied on the use of elemental formulas in children with intestinal failure (IF). Blended food diets via a gastrostomy tube have been reported to improve feeding tolerance in pediatric populations receiving long-term enteral nutrition therapy. Complex macronutrients have been shown to stimulate intestinal adaptation in animal models. We report on our experience in children with IF who had an overall improvement in stool output when transitioned from an elemental formula to a tube feeding formula with real food ingredients (TFRF). Data were collected in a retrospective chart review of children with IF, >1 year of age, who were receiving enteral nutrition via continuous infusion, bolus feeding, or both. Indications for the TFRF trial were diarrhea or inconsistent stooling patterns. Ten children with a mean small bowel length of 48.3 cm were trialed on TFRF. Nine of 10 (90%) children tolerated the transition to 100% TFRF, of which 7 of 9 (78%) had their entire colon in continuity. The average age at successful transition was 29.2 months, and the average length of time to transition to 100% TFRF was 67.3 days. TFRF is well tolerated in children >1 year of age with IF; it also improves their stooling patterns. A commercially available TFRF is a cost-effective and nutritionally adequate means of providing nutrition to this patient population.

Effects of Ethanol Lock Therapy on Central Line Infections and Mechanical Problems in Children With Intestinal Failure.

OBJECTIVES: Although use of 70% ethanol lock therapy (ELT) has been shown to decrease the rate of catheter-related bloodstream infections (CRBSIs) in patients with intestinal failure and central venous catheters (CVCs), concerns have been raised about its association with higher rates of mechanical problems and CVC replacements (CVC-Rs). We sought to compare the rates of CRBSI, mechanical problems, and CVC-Rs in a cohort of pediatric patients with intestinal failure, with and without ELT (ELT+ and ELT-, respectively). METHODS: Data were collected in a retrospective chart review from February 2007 to May 2014. Mann-Whitney and Wilcoxon signed-rank tests were used to compare nonparametric and paired data, respectively. RESULTS: Twenty-nine children had 9033 catheter days (CDs). The ELT+ group (vs ELT-) had lower rate of infection and significantly fewer CVC-Rs due to infection but significantly more mechanical events and related CVC-Rs with significantly shorter mean CVC survival. In 13 children who had a pre-ELT and post-ELT period, ELT was associated with a decrease in the rate of CVC-Rs due to infection (0.36 vs 4.74/1000 CDs, P = .046) and an increase in the rate of CVC-Rs due to mechanical problems (5.05 vs 0/1000 CDs, P = .018). CONCLUSIONS: While ELT+ is associated with a lower rate of CRBSIs and related CVC-Rs, it is also associated with higher rates of mechanical problems and related CVC-Rs. In addition to investigating the ideal concentration, duration, and timing of ELT to preserve the integrity of the CVC, alternatives to exclusively ethanol-based lock solutions should be developed.

Fecal Transplantation Successfully Treats Recurrent D-Lactic Acidosis in a Child With Short Bowel Syndrome.

D-lactic acidosis can occur in patients with short bowel syndrome (SBS) when excessive malabsorbed carbohydrate (CHO) enters the colon and is metabolized by colonic bacteria to D-lactate. D-lactate can be absorbed systemically, and increased serum levels are associated with central nervous system toxicity manifested by confusion, ataxia, and slurred speech. Current therapy, usually directed toward suppressing intestinal bacterial overgrowth and limiting ingested CHO, is not always successful. Fecal transplantation, the infusion of donor feces into a recipient's intestinal tract, has been used for decades to treat recurrent Clostridium difficile infection, and case reports document its use in the successful treatment of constipation, diarrhea, and abdominal pain. The exact mechanism of action is unknown, but it is surmised that the alteration of the intestinal microbiome, as well as the reintroduction of potential beneficial microbes, helps mediate disease. Here we present the case of a child with SBS and recurrent, debilitating D-lactic acidosis, which was successfully treated with fecal transplantation.

The Fecal Microbiome in Pediatric Patients With Short Bowel Syndrome.

BACKGROUND: Changes in the intestinal microbiome of patients with short bowel syndrome (SBS) are thought to significantly affect clinical outcome. These changes may not only delay enteral diet advancement but may also predispose patients to bacterial translocation, bacteremia, and liver disease. Patients with SBS are thought to be more susceptible to changes in gut microbial communities due to intestinal dysmotility and/or lack of anatomic safeguards such as the ileocecal valve. MATERIALS AND METHODS: We analyzed the bacterial composition of 21 fecal specimens from 9 children with SBS and 8 healthy children ages 4 months to 8 years by 16S ribosomal RNA gene sequencing. The sequences were quality filtered and analyzed using QIIME, the Ribosomal Database Project Classifier, and the randomForest supervised learning algorithm. RESULTS: The fecal microbiome of patients with SBS is different from that of healthy controls. Stool from patients with SBS had a significantly greater abundance of the bacterial classes Gammaproteobacteria and Bacilli. Stool from patients with SBS who experienced increased stool frequency tended to have increased abundance of Lactobacillus (P = .057) and decreased abundance of Ruminococcus. CONCLUSION: This study shows that the fecal microbiome of patients with SBS is significantly different from that of healthy controls when analyzed by 16S metagenomics. Differences in the composition and function of gut microbiomes in children with SBS may affect bowel physiology, and these findings may provide new opportunities for intestinal rehabilitation and clinical management.