scholarly journals Su1079 – Clinical Escherichia Coli Nf73-1 Isolated from a Patient with Nonalcoholic Steatohepatitis Induces Liver Injury Through Impairing Intestinal Barrier Function

2019 ◽  
Vol 156 (6) ◽  
pp. S-1269
Author(s):  
Yang Song ◽  
Zhe Wu ◽  
Jun Xu ◽  
Yujing Chi ◽  
Na Wu ◽  
...  
2021 ◽  
Author(s):  
Dingfa Wang ◽  
Luli Zhou ◽  
Hanlin Zhou ◽  
Guanyu Hou

Abstract Background: The effects of dietary supplementation with guava leaf extracts (GE) on growth performance, diarrhea and intestinal barrier function, as well as associated with its modulation of serum and fecal metabolic changes in weaned piglets challenged by enterotoxigenic Escherichia coli (ETEC) were investigated.Method: Fifty weaned piglets (Duroc × Yorkshire × Landrace) from 5 pens (2 piglets per pen) were randomly divided into five groups: blank control group (BC), negative control group (NC), or those supplemented with 50 mg kg-1 (S50), 100 mg kg-1 (S100), or 200 (S200) mg kg-1 diet GE, respectively. On day 4, all piglets (except for BC) were orally challenged with about 1.0 × 109 colony-forming units (CFU) enterotoxigenic ETEC. After 28-day trial, growth performance, diarrhea incidence, intestinal barrier function and metabolomics of serum and fecal were investigated.Results: We demonstrated that dietary supplementation with GE (50-200 mg kg-1) reduced diarrhea incidence of piglets and increased expression of intestinal tight junction proteins (ZO-1, Occludin, Claudin-1) (P < 0.05) and sodium hydrogen exchanger 3 (NHE3) (P < 0.05). Moreover, dietary supplementation with GE (50-200 mg kg-1) upregulated level of tetrahydrofolic acid (THF) and reversed higher level of nicotinamide-adenine dinucleotide phosphate (NADP) caused by ETEC in serum compared with NC group (P < 0.05), and enhanced antioxidant ability of piglets. In addition, dietary addition with GE (100 mg kg-1) reversed the lower level of L-pipecolic acid caused by ETEC in feces compared with NC group (P < 0.05), and decreased oxidative stress response of piglets. Further, there were no differences (P > 0.05) in the final weight, average daily feed intake (ADFI) and F/G among dietary groups during the overall period, and piglets in S50 group has the higher average daily gain (ADG). Conclusion: Dietary supplementation with 50-200 mg kg-1 GE reduced diarrhea incidence of weaned piglets challenged by ETEC and exhibited positive effect on improving intestinal barrier function. Meanwhile, dietary addition with GE organized and redistributed energy resources through similar or dissimilar metabolic pathways, and finally enhanced antioxidant ability of piglets challenged by ETEC.


2021 ◽  
Vol 12 ◽  
Author(s):  
Xiao-Han Tang ◽  
Marta Melis ◽  
Karen Mai ◽  
Lorraine J. Gudas ◽  
Steven E. Trasino

Alcohol liver disease (ALD) is a major cause of liver-related mortality globally, yet there remains an unmet demand for approved ALD drugs. The pathogenesis of ALD involves perturbations to the intestinal barrier and subsequent translocation of bacterial endotoxin that, acting through toll-like receptor 4 (TLR4), promotes hepatic inflammation and progression of ALD. In the present study we investigated the ability of fenretinide (Fen) [N-(4-hydroxyphenyl) retinamide], a synthetic retinoid with known anti-cancer and anti-inflammatory properties, to modulate intestinal permeability and clinical hallmarks of ALD in a mouse model of chronic ethanol (EtOH) exposure. Our results show that EtOH-treated mice had reductions in mRNA and protein expression of intestinal tight junction proteins, including claudin one and occludin, and increases in intestinal permeability and endotoxemia compared to pair-fed mice. Also, EtOH-treated mice had marked increases in hepatic steatosis, liver injury, and expression of pro-inflammatory mediators, including TNF-α, and TLR4-positive macrophages, Kupffer cells, and hepatocytes in the intestines and liver, respectively. In contrast, EtOH + Fen-treated mice were resistant to the effects of EtOH on promoting intestinal permeability and had higher intestinal protein levels of claudin one and occludin. Also, EtOH + Fen-treated mice had significantly lower plasma levels of endotoxin, and reductions in expression of TNF-α and TLR4 positive macrophages, Kupffer cells, and hepatocytes in the intestine and liver. Lastly, we found that EtOH + Fen-treated mice exhibited major reductions in hepatic triglycerides, steatosis, and liver injury compared to EtOH-treated mice. Our findings are the first to demonstrate that Fen possesses anti-ALD properties, potentially through modulation of the intestinal barrier function, endotoxemia, and TLR4-mediated inflammation. These data warrant further pre-clinical investigations of Fen as a potential anti-ALD drug.


2021 ◽  
Vol 8 ◽  
Author(s):  
Dingfa Wang ◽  
Luli Zhou ◽  
Hanlin Zhou ◽  
Guanyu Hou

The effects of dietary supplementation with guava leaf extracts (GE) on intestinal barrier function and serum and fecal metabolome in weaned piglets challenged by enterotoxigenic Escherichia coli (ETEC) were investigated. In total, 50 weaned piglets (Duroc × Yorkshire × Landrace) from 25 pens (two piglets per pen) were randomly divided into five groups: BC (blank control), NC (negative control), S50 (supplemented with 50 mg kg−1 diet GE), S100 (100 mg kg−1 diet GE), and S200 (200 mg kg−1 diet GE), respectively. On day 4, all groups (except BC) were orally challenged with enterotoxigenic ETEC at a dose of 1.0 × 109 colony-forming units (CFUs). After treatment for 28 days, intestinal barrier function and parallel serum and fecal metabolomics analysis were carried out. Results suggested that dietary supplementation with GE (50–200 mg kg−1) increased protein expression of intestinal tight junction proteins (ZO-1, occludin, claudin-1) (p &lt; 0.05) and Na+/H+ exchanger 3 (NHE3) (p &lt; 0.05). Moreover, dietary supplementation with GE (50–200 mg kg−1) increased the level of tetrahydrofolic acid (THF) and reversed the higher level of nicotinamide-adenine dinucleotide phosphate (NADP) induced by ETEC in serum compared with the NC group (p &lt; 0.05), and enhanced the antioxidant capacity of piglets. In addition, dietary addition with GE (100 mg kg−1) reversed the lower level of L-pipecolic acid induced by ETEC in feces compared with the NC group (p &lt; 0.05) and decreased the oxidative stress of piglets. Collectively, dietary supplementation with GE exhibited a positive effect on improving intestinal barrier function. It can reprogram energy metabolism through similar or dissimilar metabolic pathways and finally enhance the antioxidant ability of piglets challenged by ETEC.


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