Biology subjects

Burrin, D.

Publications and source records attributed to Burrin, D..

4 recordsLinked to original sources

bioRxiv2026

Pharmacokinetics and Efficacy of the FimH Inhibitor Sibofimloc in Preventing Necrotizing Enterocolitis in Preterm Piglets

Necrotizing enterocolitis (NEC) is a disease in preterm infants associated with an increased abundance of Enterobacteriaceae. FimH, a mannose-binding adhesin on Enterobacteriaceae type 1 fimbriae, mediates mucosal attachment and TLR4-dependent inflammatory cascades. We evaluated the safety, pharmacokinetics, and efficacy of an oral FimH inhibitor (Sibofimloc) to reduce Enterobacteriaceae colonization and prevent NEC in preterm piglets. We performed a 9-d dose-escalation safety study (10, 25, 50 mg/kg BID) assessing absorption and tolerability and a 10-d randomized efficacy study. Piglets in the efficacy study received an infant formula diet with or without oral sibofimloc (40 mg/kg BID), or donor human milk (DHM) as a healthy control. NEC incidence, tissue histopathology, and gut microbiota composition via metagenomic whole-genome sequencing (WGS) were evaluated. Systemic exposure data reveal that sibofimloc was dose-dependently absorbed, while plasma levels decreased from postnatal day 2 to day 8, indicating reduced drug absorption with maturation of the intestinal barrier. Treatment with sibofimloc did not reduce NEC incidence (100% in sibofimloc in formula controls) or severity, whereas DHM-fed piglets experienced 0% NEC. Sibofimloc-treated animals exhibited significantly reduced crypt depths, demonstrating heightened mucosal injury and impaired regenerative capacity. WGS revealed that sibofimloc-treated animals maintained a gut luminal microbiota composition similar to untreated formula controls, dominated by Clostridium perfringens (C. perfringens). Selective targeting of FimH-expressing Enterobacteriaceae was insufficient to prevent NEC or alter the gut microbiota in this preterm piglet model, underscoring the complexity of NEC-associated microbial communities and suggesting that additional microbial targets and other colonization mechanisms may contribute to disease development.

microbiology↗

bioRxiv2026

Evaluation of a Novel Recombinant Human Protein Formula Compared to Donor Human Milk and Standard Formula in Neonatal Piglets

BackgroundDespite the advancements in infant nutrition, a gap still exists in the nutritional composition bioactive ingredients between infant formula and human milk. We developed a next-generation, proof-of-concept infant formula that contains recombinant human milk proteins. ObjectiveTo determine the impact of a novel infant formula (H1) on organ growth and development, and intestinal function compared to donor human milk (DHM) and standard infant formula (S) in a term piglet model. MethodsTerm piglets delivered via cesarean section were fed either a donor human milk (DHM) control, the investigational formula (H1), or infant formula (S) for 10 days. On d 10, a blood sample and tissues were collected. ResultsThere was no difference (P > 0.05) in piglet growth, although H1 piglets had a smaller relative stomach and liver than DHM and S piglets. H1 piglets had higher (P < 0.05) interleukins in the distal ileum, but no other systemic cytokines were elevated compared to the DHM and S piglets. H1 piglet small intestinal histology was similar (P > 0.05) to that of DHM and S piglets. Additionally, H1 piglets had either the same (P > 0.05) or higher (P < 0.05) amino acids in circulation compared to DHM and S piglets. Recombinant human proteins had either similar (P > 0.05) or lower (P < 0.05) activity compared to the native human proteins when assessing the individual ingredients in the H1 formula. ConclusionH1 formula was noninferior to DHM and S based on growth, small intestinal histology and plasma amino acid endpoints when fed to neonatal piglets. These findings warrant further studies to use the neonatal piglet as a model to evaluate more in-depth outcomes of health and safety for new infant formulas. Lay SummaryA novel piglet study shows a hypoallergenic, next-generation infant formula containing recombinant human milk proteins rivals donor human milk and standard formula for growth, gut health, and nutrient status.

physiology↗

bioRxiv2025

Pre- and postnatal 1,4-phenylene di-isothiocyanate treatment does not induce bile duct injury in neonatal pigs

BackgroundBiliary atresia (BA) is the leading cause of pediatric liver transplants, however; the cause of biliary atresia (BA) is unknown. Furthermore, the most common treatment for this disease is with a surgical procedure, which has a greater than 50% failure rate after 5 years. Due to a lack of proper animal models to study the pathology of the disease, little progress has been made in the field. ObjectiveThe objective of this study was to test whether pre and postnatal 1,4-phenylene di-isothiocyanate (DITC) would induce bile duct injury and cholestasis in neonatal pigs. MethodsPregnant sows received DITC once at gestation week 5 (100 mg/kg; n=2), or 3 times at gestation weeks 5, 6, and 7 (100 mg/kg each; n=2), or twice per week at gestation weeks 5-16 (15 mg/kg each; n=2). Cesarian-delivered piglets of the sows were randomly assigned to receive approximately 200 mg/kg DITC on days two, four, and six of life or to remain untreated. Piglets were fed enterally and collected blood samples were monitored for markers of liver injury for 14 days. At the end of 14 days, tissues were weighed and collected for immunohistochemistry and histopathology scoring. ResultsPiglets from sows that received DITC for 11 weeks had lower (P < 0.05) final body weight and daily gain compared to other treatments. Piglets from sows that received DITC for 11 weeks had a transient increase in gamma-glutamyl transferase. Liver histological scoring and analysis also did not show signs of BA. Piglets that received DITC from 11-week DITC-treated sows had elevated hepatic bile acids (P < 0.05), but there was no difference in serum bile acids (P > 0.05). ConclusionsThe administration of DITC to pregnant sows and neonatal piglets did not result in the development of bile duct or hepatic injury.

pathology↗

bioRxiv2020

New Insights and Enhanced Human Norovirus Cultivation in Human Intestinal Enteroids

Human noroviruses (HuNoVs) are the leading cause of epidemic and sporadic acute gastroenteritis worldwide. We previously demonstrated human intestinal stem cell-derived enteroids (HIEs) support cultivation of several HuNoV strains. However, HIEs did not support virus replication from every HuNoV-positive stool sample, which led us to test and optimize new media conditions, identify characteristics of stool samples that allow replication, and evaluate consistency of replication over time. Optimization of our HIE-HuNoV culture system has shown that: 1) A new HIE culture media made with conditioned medium from a single cell line and commercial media promote robust replication of HuNoV strains that replicated poorly in HIEs grown in our original culture media made with conditioned media from 3 separate cell lines; 2) GI.1, eleven GII genotypes (GII.1, GII.2, GII.3, GII.4, GII.6, GII.7, GII.8, GII.12, GII.13, GII.14 and GII.17) and six GII.4 variants, can be cultivated in HIEs; 3) successful replication is more likely with virus in stools with higher virus titers; 4) GII.4_Sydney_2012 virus replication was reproducible over three years; and 5) HuNoV infection is restricted to the small intestine, based on replication in duodenal and ileal HIEs but not colonoids from the same donors. These results improve the HIE culture system for HuNoV replication. Use of HIEs by several laboratories worldwide to study the molecular mechanisms that regulate HuNoV replication confirms the usefulness of this culture system and our optimized methods for virus replication will advance the development of effective therapies and methods for virus control. ImportanceHuman noroviruses (HuNoVs) are highly contagious and cause acute and sporadic diarrheal illness in all age groups. In addition, chronic infections occur in immunocompromised cancer and transplant patients. These viruses are antigenically and genetically diverse and there are strain-specific differences in binding to cellular attachment factors. In addition, new discoveries are being made on strain-specific differences in virus entry and replication and the epithelial cell response to infection in human intestinal enteroids. Human intestinal enteroids are a biologically-relevant model to study HuNoVs; however, not all strains can be cultivated at this time. A complete understanding of HuNoV biology thus requires cultivation conditions that will allow the replication of multiple strains. We report optimization of HuNoV cultivation in human intestinal enteroid cultures to increase the numbers of cultivatable strains and the magnitude of replication, which is critical for testing antivirals, neutralizing antibodies and methods of virus inactivation.

microbiology↗