Xuejin Gao

N-3 polyunsaturated fatty acid-enriched lipid emulsion improves Paneth cell function via the IL-22/Stat3 pathway in a mouse model of total parenteral nutrition

Total parenteral nutrition (TPN) is a life-saving therapy for patients with gastrointestinal dysfunction or failure. Long-term TPN impairs gut barrier function and contributes to infections and poor clinical outcomes. However, the underlying mechanisms of TPN-related gut barrier damage have not been fully elucidated, and effective measures are still rare. Here, we compared the effects of a predominantly n-6 polyunsaturated fatty acids emulsion (PUFAs; Intralipid) and a lipid emulsion containing n-3 PUFAs (Intralipid plus Omegaven) on antimicrobial peptides produced by Paneth cells. Our results show for the first time that n-3 PUFAs markedly ameliorated intestine atrophy, and increased protein levels of lysozyme, RegIIIγ, and α-cryptdin 5, and their mRNA expression, compared to the n-6 PUFAs emulsion. Importantly, our study reveals that downregulation of IL-22 and phosphorylated Stat3 (p-Stat3) is associated with Paneth cell dysfunction, which may mediate TPN-related gut barrier damage. Lastly, n-3 PUFAs upregulated levels of IL-22 and increased the p-Stat3/Stat3 ratio in ileal tissue, suggesting that n-3 PUFAs improve Paneth cell function through activation of the IL-22/Stat3 pathway. Therefore, our study provides a cogent explanation for the beneficial effects of n-3 PUFAs, and indicates the IL-22/Stat3 pathway as a promising target in the treatment of TPN-related gut barrier damage.

Bedside electromagnetic-guided placement of nasoenteral feeding tubes among critically Ill patients: A single-centre randomized controlled trial

Purpose: We aimed to compare the effectiveness of EM‐guided and endoscopic nasoenteral feeding tube placement among critically ill patients. Materials and methods: We performed a single‐center, randomized controlled trial among 161 adult patients admitted to intensive care units (ICUs) requiring nasoenteral feeding. Patients were randomly assigned to EM‐guided or endoscopic nasoenteral feeding tube placement (1:1). The primary end point was the total success rate of correct jejunal placement. Results: This was achieved in 74/81 and 76/80 patients who underwent EM‐guided and endoscopic jejunal tube placements, respectively (91.4% vs. 95%; relative risk, 0.556; [CI], 0.156–1.980; P = 0.360). The EM‐guided group had more placement attempts, longer placement time, and shorter inserted nasal intestinal tube length. However, they had shorter total placement procedure duration and physicians order–tube placement and order–start of feeding intervals. The EM‐guided group had higher discomfort level and recommendation scores and lesser patient costs. This trial is registered at Chinese Clinical Trials Registry (ChiCTR‐IOR‐17011737). Conclusion: Bedside EM‐guided placement is as fast, safe, and successful as endoscopic placement and may be considered the preferred technique in critically ill patients.

Aryl hydrocarbon receptor/IL-22/Stat3 signaling pathway is involved in the modulation of intestinal mucosa antimicrobial molecules by commensal microbiota in mice:

Compelling evidence demonstrates the crucial role of the commensal microbiota in host physiology and the detrimental effects of its perturbations following antibiotic treatment. However, the effects of commensal microbiota on intestinal mucosa antimicrobial molecules have not been elucidated systematically. Here, we investigate the impacts of antibiotic-induced depletion and subsequent restoration of the intestinal microbiota on the murine antimicrobial molecules in intestinal mucosa. Our results demonstrate that depletion of commensal microbiota leads to intestinal mucosa atrophy and reduction of antimicrobial molecules, including lysozyme, regenerating islet-derived protein 3 gamma (RegIIIγ), and cryptdin 5 mRNA, whereas subsequent reconstitution of intestinal microbiota by fecal microbiota transplantation (FMT) rescues mucosa morphology and antimicrobials. Importantly, our study shows that down-regulation of aryl hydrocarbon receptor (AhR), interleukin-22 (IL-22), and phosphorylated Stat3 (p-Stat3) is associated with decreased antimicrobials, which might mediate the antibiotic-associated intestinal mucosa injury. Last, exogenous activation of the AhR/IL-22/Stat3 signaling pathway with the AhR agonist 6-formylindolo(3,2-b)carbazole (Ficz) rescued antimicrobial molecule levels markedly after antibiotic treatment to levels similar to those following reconstitution of intestinal microbiota by FMT. Together, our results demonstrate that the AhR/IL-22/Stat3 signaling pathway is involved in the modulation of intestinal mucosa antimicrobial molecules by commensal microbiota and suggest this pathway as a promising target in the treatment of antibiotic-associated gut barrier damage.

N-3 polyunsaturated fatty acids ameliorate hepatic steatosis via the PPAR-α/CPT-1α pathway in a mouse model of parenteral nutrition

Parenteral nutrition (PN) is one of the basic therapies for patients with intestinal failure; however, hepatic steatosis associated with PN limits the long-term use of PN. N-3 polyunsaturated fatty acids (PUFAs) have been used to improve clinical outcomes of patients receiving PN; however, the mechanisms by which n-3 PUFAs ameliorate hepatic steatosis remain unclear. In the present study, C57BL/6J mice were randomly assigned to three treatment groups, namely, enteral nutrition (EN), n-3 PUFAs, and n-6 PUFAs. Additionally, MK 886 was used to inhibit PPAR-α. After 7 days of intervention, mice were sacrificed, and liver tissue and serum samples were collected. Results from liver weight and liver triglyceride measurements and Oil Red O staining showed that n-3 PUFAs significantly reduced the liver triglyceride levels. In addition, treatment with n-3 PUFAs resulted in a greater decrease in serum triglyceride and low-density lipoprotein cholesterol levels compared to n-6 PUFAs. The key enzymes involved in FA oxidation, namely, PPAR-α and CPT-1α, were significantly restored at both the mRNA and protein levels in the n-3 PUFAs group. However, the benefits of n-3 PUFAs in improving serum and liver TG levels were abolished when the PPAR-α/CPT-1α pathway was blocked by MK 886. The results of this study indicated that n-3 PUFAs ameliorated the PN-associated hepatic steatosis by activating the PPAR-α/CPT-1α pathway. The present study provided a reliable scientific basis supporting the potential beneficial effects of n-3 PUFAs for improving hepatic steatosis in patients receiving long-term parenteral nutrition.

SUN-P009: Hemorrhagic Shock-Resuscitation Injury Decreases Fatty Acid Oxidation and Peroxisome Proliferator-Activated Receptor in the Skeletal Muscle

Objective: The study was designed to study the influence of hemorrhagic shock-resuscitation injury on mice fatty acid oxidation and peroxisome proliferator-activated receptor expression. Methods: 48 C57 BL /6 mice were assigned to 6groups. One was sham group without any surgery. According to the different time when the mice were sacrificed after hemorrhagic shock-resuscitation injury,the other 5groups were defined as Day 1 postoperative group( D1 group),Day 2 postoperative group( D2 group),Day 3 postoperative group( D3 group),Day4 postoperative group( D4 group) and Day 5 postoperative group( D5 group). Soleus tissue were collected for the protein and gene expression related to fatty acid oxidation. Results: After hemorrhagic shock-resuscitation injury,the protein and gene expression of CPT-1b,FATP-1,PPAR-αand PPAR-β in muscle tissue decreased significantly.Conclusion: Hemorrhagic shock-resuscitation injury may decrease the nuclear hormone receptors in muscle which regulate the lipid metabolism and impair the fat β-oxidation.