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Background: Thisstudy aimed to investigate the impact of fish oil–based lipid emulsion (FO) on enterohepatic injuries and intestinal microbiota in piglets of parenteral nutrition (PN). Methods: Newborn piglets were divided into three groups, including enteral diet (the controls), PN with 100% FO and PN with medium‐chain triglyceride/long‐chain triglyceride–based lipid emulsion (MCT/LCT) for 14 days. Serum biochemical indicators, hepatic and intestinal histology, and expression of genes associated with inflammation, oxidative stress, and lipid metabolism were measured. The bile acid (BA) profiles in serum and the taxonomic composition of the gut microbiome in different intestinal segments were analyzed. Results: Compared with MCT/LCT–piglets, FO reduced inflammation, promoted fatty acid oxidation, and decreased oxidative stress in the liver. In the intestine, FO decreased intestinal inflammation and intestinal permeability, leading to reduced lipopolysaccharide entry into the blood circulation relative to MCT/LCT–piglets. PN groups have dominant contents of Proteobacteria and Bacteroides, whereas the control group have Firmicutes at the phylum level. FO altered the taxonomic compositions of the gut microbiome in different segments, increased the relative abundance of Bacteroidaceae in ileum, and Rikenellaceae and Ruminococcaceae in the colon. FO treatment shifted BA composition ratio in serum and had a lower ratio of secondary BAs to primary BAs. Conclusion: FO alleviates PNLAD and intestinal injury by regulating the homeostasis of BAs' enterohepatic circulation and altering microbiota composition in different intestinal segments. [ABSTRACT FROM AUTHOR]

Background: The breakpoint cluster region (BCR) is a protein that originally forms a fusion protein with c‐Abl tyrosine kinase and induces leukemia. Researchers have shown that BCR is enriched in the central nervous system and may contribute to neurological disorders. We aimed to investigate the physiological function of BCR in neural development in the gastrointestinal (GI) tract and brain. Methods: Whole‐exome sequencing was used to screen for mutations in the BCR. Bcr knockout mice (Bcr−/−, ΔExon 2–22) were generated using the CRISPR/Cas9 system. Transit of carmine red dye and glass bead expulsion assays were used to record total and proximal GI transit and distal colonic transit. Key Results: In an infant with pediatric intestinal pseudo‐obstruction, we found a heterozygous de novo mutation (NM_004327.3:c.3072+1G>A) in BCR. Bcr deficiency mice (Bcr−/−) exhibited growth retardation and impaired gastrointestinal motility. Bcr−/− mice had a prolonged average total GI transit time with increased distal colonic transit and proximal GI transit in isolation. Morphology analysis indicated that Bcr−/− mice had a less number of neurons in the submucosal plexus and myenteric plexus. Bcr−/− mice exhibited apparent structural defects in the brain, particularly in the cortex. Additionally, Bcr− depletion in the mouse cortex altered the expression of Ras homologous (Rho) family small GTPases. Conclusions and Inferences: BCR mutations are associated with intestinal obstruction in children. Loss of Bcr can cause intestinal dysmotility and brain developmental defects may via regulation of Rho GTPases. [ABSTRACT FROM AUTHOR]

Objective: Long-term parenteral nutrition (PN) causes PN-associated liver disease, for which therapeutic approaches are limited. This study aimed to investigate the effects of Lactobacillus plantarum CGMCC 1258 (LP) on liver and intestinal injury in PN-fed neonatal piglets., Methods: The piglets received PN with or without oral LP for 14 days. The levels of liver enzymes and inflammatory markers were measured using biochemical kits and quantitative real-time polymerase chain reaction. Serum fibroblast growth factor 19 (FGF19) was detected using an enzyme-linked immunosorbent assay. The bile acid (BA) profiles in the liver, serum, and intestinal contents were determined using ultraperformance liquid chromatography coupled with mass spectrometry. The composition of intestinal bacteria was analyzed with 16S rRNA gene amplicon sequencing., Results: LP supplementation was associated with improved markers of liver disease, inflammation, and oxidative stress in PN-fed piglets. Moreover, markers of intestinal injury and inflammation were alleviated by LP in PN-fed piglets. Mechanistically, LP increased the abundance of Lactobacillus in ileal contents and stimulated FGF19 expression in ileal mucosa. Subsequently, it increased the expression of small heterodimer partner (SHP) and inhibited cholesterol 7α-hydroxylase (CYP7A1) expression in the liver. Additionally, LP altered the systemic composition and metabolism of BAs., Conclusions: LP alleviated liver and intestinal injury in PN-fed neonatal piglets by altering the composition of intestinal bacteria and BAs., (© 2022 American Society for Parenteral and Enteral Nutrition.)