scholarly journals Dietary sophorolipid accelerates growth by modulation of gut microbiota population and intestinal environments in broiler chickens

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Min-Jin Kwak ◽  
Min-Young Park ◽  
Yong-Soon Choi ◽  
Junghwan Cho ◽  
Duleepa Pathiraja ◽  
...  
Keyword(s):  
Body Weight ◽  
Barrier Function ◽  
Broiler Chickens ◽  
Pathogenic Bacteria ◽  
Inflammatory Cytokine ◽  
Intestinal Inflammation ◽  
Defense System ◽  
Villus Height ◽  
Treatment Groups ◽  
Gut Barrier Function

Abstract Background Gut is a crucial organ for the host’s defense system due to its filtering action of the intestinal membrane from hazardous foreign substances. One strategy to strengthen the gut epithelial barrier function is to upregulate beneficial microflora populations and their metabolites. Sophorolipid (SPL), which is a glycolipid bio-surfactant, could increase beneficial microflora and decrease pathogenic bacteria in the gastrointestinal tract. Therefore, herein, we conducted an experiment with broiler chickens to investigate the fortifying effects of SPL on the host’s gut defense system by modulating the microbiota population. Methods A total of 540 1-day-old chicks (Ross 308) were used, and they were immediately allotted into three treatment groups (6 replications with 30 chicks/pen) according to their initial body weight. The dietary treatments consisted of CON (basal diet), BAM (10 mg/kg bambermycin), and SPL (10 mg/kg SPL). During the experiment, birds freely accessed feed and water, and body weight and feed intake were measured at the end of each phase. On d 35, birds (one bird/pen) were sacrificed to collect jejunum and cecum samples. Results Dietary SPL and BAM supplementation significantly accelerated birds’ growth and also significantly improved feed efficiency compared to CON. Intestinal microbial community was significantly separated by dietary SPL supplementation from that of CON, and dietary SPL supplementation significantly increased Lactobacillus spp. and Akkermansia muciniphila. Moreover, birds fed with dietary SPL also showed the highest concentration of cecal butyrate among all treatment groups. Gut morphological analysis showed that dietary SPL significantly increased villus height, ratio of villus height to crypt depth, goblet cell numbers, and the gene expression levels of claudin-1 and mucin 2. Additionally, dietary SPL significantly decreased the mRNA expression level of pro-inflammatory cytokine, interleukin-6, and increased that of anti-inflammatory cytokine, interleukin-10, compared to other treatments. Conclusions Dietary SPL increases the beneficial bacterial population and butyrate concentration, which leads to a strengthened gut barrier function. In addition, the intestinal inflammation was also downregulated by dietary SPL supplementation.

scholarly journals Pertambahan Bobot Badan dan Waktu Pembusukan Daging Ayam Broiler yang Diberi Ekstrak Jaloh Dikombinasi dengan Kromium

2010 ◽  
Vol 10 (2) ◽  
pp. 21-26
Author(s):  
Sugito Sugito ◽  
Erdiansyah Rahmi ◽  
Azhari Azhari ◽  
M. Isa
Keyword(s):  
Drinking Water ◽  
Body Weight ◽  
Heat Stress ◽  
Broiler Chickens ◽  
Room Temperature ◽  
The Body ◽  
Feed Ratio ◽  
Treatment Groups ◽  
Randomized Design ◽  
Completely Randomized Design

The gain body weight and Spoilage of meat broiler which giving jaloh extract to combine with chromiumABSTRACT. A study was conducted on broiler chickens under heat stress to evaluate the effect of combined jaloh (Salix tetrasperma Roxb) extract with chromium mineral in the body weight, value of feed ratio conversion, and time to meat to become decomposed. Twenty four of 20-day old Cobb female broiler chickens were randomly assigned and divided to 4 treatment groups. Completely randomized design was used in this study. The treatments were as follows: 1) chickens given no heat stress and jaloh extract nor chromium (tCp); 2) chickens under heat stress without given jaloh extract nor chromium (Cp); 3) chickens under heat stress and given jaloh extract in 1.000 mg/lt drinking water (Cp+Ej); and 4) chickens under heat stress, given jaloh extract in 1.000 mg/lt drinking water, and chromium in 1.000 ug/lt drinking water (Cp+Ej+Cr). Heat stress given was 33 ± 1oC of cage temperature during 4 hours per day within 15 days. Jaloh extract and chromium treatments in drinking water were given at 2 hour before cage temperature reaching 33 ± 1oC and were stopped being given after 1 hour, when cage temperature back to room temperature. On the 16th day of the study chickens were measured before slaughtered. Samples obtained were chicken meat that taken from breast part (musculus pectoralis). The result suggested that either giving jaloh extract per se at the dose of 1.000 mg/lt in drinking water or combine it with chromium that given two hours before cage temperature reaching 33 ± 1oC, can prevent chickens from decreasing their body weight, decreasing value of feed ratio convertion, and extending time to meat to become decomposed.

scholarly journals Effect of dietary esterified glucomannan on performance, serum biochemistry and haematology in broilers exposed to aflatoxin

2011 ◽  
Vol 50 (No. 1) ◽  
pp. 31-39 ◽  
Author(s):  
H. Basmacıoglu ◽  
H. Oguz ◽  
M. Ergul ◽  
R. Col ◽  
Birdane YO
Keyword(s):  
Body Weight ◽  
Adverse Effects ◽  
Total Protein ◽  
Broiler Chickens ◽  
Body Weight Gain ◽  
Serum Biochemistry ◽  
Inorganic Phosphorus ◽  
Broiler Chicks ◽  
Treatment Groups ◽  
Dietary Concentration

The amelioration of aflatoxicosis in broiler chickens was examined by feeding two concentrations of yeast component (esterified glucomannan; EG). EG, incorporated into the diet at 0.5 and 1 g/kg, was evaluated for its ability to reduce the detrimental effects of 2 mg total aflatoxin (AF; 82.72% AFB<sub>1</sub>, 5.50% AFB<sub>2</sub>, 10.20% AFG<sub>1</sub> and 1.58% AFG<sub>2</sub>) in diet on growing broiler chicks from 1 to 21 d of age. A total of 240 male broiler chicks (Ross-308) were divided into 6 treatment groups [control, AF, EG (0.5 g/kg), AF plus EG (0.5 g/kg), EG (1 g/kg), and AF plus EG (1 g/kg)]. Compared to the control, AF treatment significantly decreased body weight gain from week 2 onwards. AF treatment also caused significant decreases in serum total protein, albumin, total cholesterol, triglyceride, glucose, inorganic phosphorus, creatinine levels and alanine-aminotransferase (ALAT) activity but increased the aspartate-aminotransferase (ASAT) activity. Red blood cell, haematocrit, haemoglobin, thrombocyte, and lymphocyte counts and tibial crude ash levels were significantly reduced by AF treatment, while significant increases were seen in heterophil counts. The addition of EG (1 g/kg) to an AF-containing diet significantly improved the adverse effects of AF on haematological parameters, total protein, albumin values and ASAT activity. EG (1 g/kg) also partially improved body weight gains (59%) and the other biochemical parameters influenced by AF treatment. The addition of EG (both 0.5 and 1 g/kg) to the AF-free diet did not cause any considerable changes in the investigated values. These results clearly indicated that EG (1 g/kg) addition effectively diminished the adverse effects of AF on the investigated values. Also, the higher dietary concentration of EG (1 g/kg) was found more effective than the lower concentration (0.5 g/kg) against the adverse effects of AF on the variables investigated in this study. &nbsp;

scholarly journals Prebiotics Fructo-, Galacto-, and Mannan-Oligosaccharide Do Not Protect against 5-Fluorouracil–Induced Intestinal Mucositis in Rats

2019 ◽  
Vol 149 (12) ◽  
pp. 2164-2173 ◽  
Author(s):  
Roger Yazbeck ◽  
Ruth J Lindsay ◽  
Mark S Geier ◽  
Ross N Butler ◽  
Gordon S Howarth
Keyword(s):  
Body Weight ◽  
Treatment Group ◽  
Myeloperoxidase Activity ◽  
Intestinal Damage ◽  
Small Intestinal Mucosa ◽  
Villus Height ◽  
Mannan Oligosaccharide ◽  
Treatment Groups ◽  
Small Intestinal ◽  
All Treatment

ABSTRACT Background Prebiotics selectively stimulate the growth of beneficial bacteria within the gastrointestinal tract, and have been investigated in human and animal studies for their capacity to improve intestinal health. Objective We investigated the prebiotics fructo-oligosaccharide (FOS), galacto-oligosaccharide (GOS), and mannan-oligosaccharide (MOS) for their potential to alleviate intestinal damage in rats. Methods Female Dark Agouti rats (6–8 wk old, 110–150 g) were allocated to 1 of the following treatment groups (n = 8/group): saline/water, saline/FOS, saline/GOS, saline/MOS, 5-fluorouracil (5FU)/water, 5FU/FOS, 5FU/GOS, and 5FU/MOS. Rats were pretreated with either 5% GOS, MOS, or FOS or vehicle (water) from day −12 to day 0. On day 0, rats received a single intraperitoneal injection of saline or 5FU. Metabolic data were recorded daily and all rats were killed on day 3. Histopathology was quantified in hematoxylin and eosin–stained sections. Intestinal sucrase and myeloperoxidase activity were quantified by biochemical assay. Fecal SCFAs—acetic, propionic, and butyric acid—were also measured. Statistical analysis was by repeated-measures, 2-factor ANOVA or Kruskal–Wallis and Mann–Whitney U test; P < 0.05 was considered statistically significant. Results Body weight was significantly decreased in all treatment groups after 5FU injection, with no change in body weight observed in any prebiotic treatment group. Total food intake was lower by ≥7% in the GOS treatment group pre-5FU than in all other groups (P < 0.05). Ileal villus height was 18% higher in GOS-treated rats pre-5FU than in respective water controls (P < 0.05). Jejunal and ileal villus height and crypt depth were significantly decreased in all treatment groups after 5FU injection, with no prebiotic effect observed. SCFAs were differentially increased in prebiotic treatment groups compared with water-only controls (P < 0.05). Conclusions FOS, GOS, and MOS have differential effects in modifying small intestinal pathology and SCFA profiles in rats with healthy and damaged small intestinal mucosa.

scholarly journals 2’-fucosyllactose (2’-FL) Supplementation Improves Gut Barrier Function and Lipid Metabolism in HF-fed Mice

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 425-425
Author(s):  
Sunhye Lee ◽  
Michael Goodson ◽  
Wendie Vang ◽  
Karen Kalanetra ◽  
Daniela Barile ◽  
...  
Keyword(s):  
Body Weight ◽  
Lipid Metabolism ◽  
Intestinal Permeability ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Gut Barrier ◽  
Low Fat ◽  
Barrier Integrity ◽  
Gut Barrier Function

Abstract Objectives 2’-fucosyllactose (2’-FL), the most predominant oligosaccharide found in human milk, acts as a prebiotic with beneficial effects on the host. The aim of this study was to determine the beneficial effect of 2’-FL on intestinal barrier integrity and metabolic functions in low-fat (LF)- and high-fat (HF)-fed mice. Methods Male C57/BL6 mice (n = 32, 8/group; 6 weeks old, JAX, CA) were counter-balanced into four weight-matched groups and fed either a low-fat (LF; 10% kcal fat with 7% kcal sucrose) or HF (45% kcal fat with 17% kcal sucrose) with or without supplementation of 2’-FL in the diet [10% (w/w), 8 weeks; LF/2’-FL or HF/2’-FL; BASF, Germany]. General phenotypes (body weight, energy intake, fat and lean mass), intestinal permeability (ex vivo in Ussing chambers), lipid profiles, and microbial metabolites were assessed. Results 2’-FL significantly attenuated the HF-induced increase in body fat mass with a trend to decrease body weight gain. 2’-FL significantly decreased intestinal permeability in LF-fed mice with a trend for a decrease in HF-fed mice. This was associated with a significant increase in interleukin-22, a cytokine known to have a protective role in intestinal barrier function. Visceral adipocyte size was significantly decreased by 2’-FL in both LF- and HF-fed mice. 2’-FL suppressed HF-induced upregulation of adipogenic transcription factors peroxisome proliferator-activated receptor gamma and sterol regulatory element binding protein-1c in the liver. Lastly, 2’-FL supplementation led to a significant elevation of lactic acid concentration in the cecum of HF-fed mice, which is known to be a product from beneficial microbes. Conclusions 2’-FL supplementation improved gut barrier integrity and lipid metabolism in mice with and without the metabolic challenge of HF feeding. These findings support the use of 2’-FL in the control of gut barrier function and metabolic homeostasis under normal and abnormal physiological conditions. Funding Sources BASF (Germany).

scholarly journals Impact of Bacterial Metabolites on Gut Barrier Function and Host Immunity: A Focus on Bacterial Metabolism and Its Relevance for Intestinal Inflammation

2021 ◽  
Vol 12 ◽  
Author(s):  
Naschla Gasaly ◽  
Paul de Vos ◽  
Marcela A. Hermoso
Keyword(s):  
Celiac Disease ◽  
Immune Responses ◽  
Bile Acids ◽  
Barrier Function ◽  
Intestinal Inflammation ◽  
Microbial Interactions ◽  
Gut Barrier Function ◽  
Gut Immunity ◽  
Tryptophan Catabolites ◽  
Secondary Bile Acids

The diverse and dynamic microbial community of the human gastrointestinal tract plays a vital role in health, with gut microbiota supporting the development and function of the gut immune barrier. Crosstalk between microbiota-gut epithelium and the gut immune system determine the individual health status, and any crosstalk disturbance may lead to chronic intestinal conditions, such as inflammatory bowel diseases (IBD) and celiac disease. Microbiota-derived metabolites are crucial mediators of host-microbial interactions. Some beneficially affect host physiology such as short-chain fatty acids (SCFAs) and secondary bile acids. Also, tryptophan catabolites determine immune responses, such as through binding to the aryl hydrocarbon receptor (AhR). AhR is abundantly present at mucosal surfaces and when activated enhances intestinal epithelial barrier function as well as regulatory immune responses. Exogenous diet-derived indoles (tryptophan) are a major source of endogenous AhR ligand precursors and together with SCFAs and secondary bile acids regulate inflammation by lowering stress in epithelium and gut immunity, and in IBD, AhR expression is downregulated together with tryptophan metabolites. Here, we present an overview of host microbiota-epithelium- gut immunity crosstalk and review how microbial-derived metabolites contribute to host immune homeostasis. Also, we discuss the therapeutic potential of bacterial catabolites for IBD and celiac disease and how essential dietary components such as dietary fibers and bacterial tryptophan catabolites may contribute to intestinal and systemic homeostasis.

scholarly journals Response and Economic Efficiency of Broiler Chickens fed graded levels of Baker's Yeast (Saccharomyces cerevisiae) supplement

2021 ◽  
Vol 43 (2) ◽  
pp. 304-313
Author(s):  
W. Buba ◽  
T. S. Olugbemi ◽  
J. J Omage ◽  
S. Duru ◽  
A. O Iyiola-Tunji
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Body Weight ◽  
Weight Gain ◽  
Treatment Group ◽  
Economic Efficiency ◽  
Broiler Chickens ◽  
Baker’S Yeast ◽  
Baker's Yeast ◽  
Yeast Saccharomyces Cerevisiae ◽  
Treatment Groups

Two hundred and fifty-five day-old Ross White strain broiler chicks were used to evaluate the Response and economic efficiency of broiler chickens fed graded levels of baker's yeast (saccharomyces cerevisiae) supplement during the harmattan season in the northern guinea savannah zone of Nigeria. There were five treatment groups for both starter and finisher phases. The experiment lasted for eight weeks. Each treatment group had three replicates with 17 birds per replicate and fifty-five birds per group in a completely randomized design (CRD). Treatments 1, 2, 3, 4 and 5 contained 0.0, 0.5, 1.0, 1.5 and 2.0% SC respectively. Results of the starter phase showed significant (P<0.05) differences in terms of final weight gain and feed conversion ratio (FCR). Treatment groups fed the control diet (0.0%), 0.5% and 1% SC had the best final body weight and body weight gain during the starter phase. The FCR was significantly (P<0.05) higher in the treatment group fed 0.5% SC during the starter phase. Mortality was higher (11.76%) in the control group compared to other treatment groups in the starter phase. During the finisher phase, treatment group fed 1.0% SC had significantly (P<0.05) higher final body weight, body weight gain and FCR. Apparent digestibility of crude protein, crude fibre, ether extract, ash, dry matter and nitrogen free extract were better in treatment groups containing SC. The economic efficiency results of this study indicated that the birds fed 1.0% SC were more profitable compared to those fed the control diet. The net profit of the treatment group fed 1.0% SC was N 650.01 compared to the control (N554.35). This study concluded that the optimum inclusion level of Baker's yeast (Saccharomyces cerevisiae) in the diet of broilers starter was 0.5% and 1.0% for finisher diet for improved performance in terms of weight gain and feed conversion ratio (FCR). It is suggested that broiler chicken farmers should be encouraged to include Baker's yeast in the diet of broiler chickens for improved weight productivity and better feed utilization.

scholarly journals Metabolome and Microbiota Analysis Reveals the Conducive Effect of Pediococcus acidilactici BCC-1 and Xylan Oligosaccharides on Broiler Chickens

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuqin Wu ◽  
Zhao Lei ◽  
Youli Wang ◽  
Dafei Yin ◽  
Samuel E. Aggrey ◽  
...  
Keyword(s):  
Propionic Acid ◽  
Broiler Chickens ◽  
Pathogenic Bacteria ◽  
Conversion Ratio ◽  
Feed Conversion Ratio ◽  
Control Group ◽  
Gut Health ◽  
Feed Conversion ◽  
Metabolome Analysis ◽  
Treatment Groups

Xylan oligosaccharides (XOS) can promote proliferation of Pediococcus acidilactic BCC-1, which benefits gut health and growth performance of broilers. The study aimed to investigate the effect of Pediococcus acidilactic BCC-1 (referred to BBC) and XOS on the gut metabolome and microbiota of broilers. The feed conversion ratio of BBC group, XOS group and combined XOS and BBC groups was lower than the control group (P &lt; 0.05). Combined XOS and BBC supplementation (MIX group) elevated butyrate content of the cecum (P &lt; 0.05) and improved ileum morphology by enhancing the ratio of the villus to crypt depth (P &lt; 0.05). The 16S rDNA results indicated that both XOS and BBC induced high abundance of butyric acid bacteria. XOS treatment elevated Clostridium XIVa and the BBC group enriched Anaerotruncus and Faecalibacterium. In contrast, MIX group induced higher relative abundance of Clostridiaceae XIVa, Clostridiaceae XIVb and Lachnospiraceae. Besides, MIX group showed lower abundance of pathogenic bacteria such as Campylobacter. Metabolome analysis showed that all the 3 treatment groups (XOS, BBC and MIX) showed lower concentrations of sorbitol and both XOS and BBC group had higher concentrations of pyridoxine levels than CT group. Besides, XOS and BBC groups enhanced the content of hydroxyphenyl derivatives 4-hydroxyphenylpyruvate 1 and 3-(3-hydroxyphenyl) propionic acid, respectively (P &lt; 0.05). Notably, MIX group enhanced both 4-hydroxyphenylpyruvate 1 and 3-(3-hydroxyphenyl) propionic acid (P &lt; 0.05). Thus, XOS and BBC may have a synergistic role to improve the performance of broilers by modulating gut microbiota and metabolome.

scholarly journals EFFECT OF PROBIOTICS AND ANTIBIOTIC SUPPLEMENTATION ON BODY WEIGHT AND HAEMATO-BIOCHEMICAL PARAMETERS IN BROILERS

2012 ◽  
Vol 3 (2) ◽  
pp. 100-104 ◽  
Author(s):  
SM Kamruzzaman ◽  
SML Kabir ◽  
MM Rahman ◽  
MW IslaM ◽  
MA Reza
Keyword(s):  
Drinking Water ◽  
Body Weight ◽  
Biochemical Parameters ◽  
Broiler Chickens ◽  
Animal Health ◽  
The Body ◽  
Control Group ◽  
Spleen Weight ◽  
Treatment Groups ◽  
Group A

The study was carried out to know the effects of probiotics (Proetxin® Boost, Novartis Bangladesh Ltd.) and antibiotic (oxytetracycline-Renamycin®, Renata Animal Health) on growth performances and haemato-biochemical parameters of "Shaver Star Bro" broiler chickens during September and October 2003. A total of 20, day old broilers were randomly selected and assigned into four equal groups n = 5) as A, B, C and D. Group A was considered as control group fed with commercial ration while groups B, C and D were fed with commercial ration with the addition of 200 mg probiotics / liter drinking water, 100 mg probiotics and 50 mg antibiotic (oxytetracycline- Renamycin®) / liter drinking water and 100 mg antibiotic (oxytetracycline- Renamycin®) / liter drinking water respectively up to 35 days of age. The results showed that the body weight gains differed significantly (p < 0.05) at the 2nd, 4th and 5th weeks of age in different treatment groups. The meat yield not differed significantly (p > 0.05). The drumstick, wing differed significantly (p < 0.01) and spleen weight differed at p < 0.05 among different groups. The mean haemato-biochemical values of Hb, ESR, PCV, heterophil, eosinophil, basophil, triglyceride, HDL, LDL, SGPT and SGOT were differed significantly (p < 0.01) in different groups. The present findings suggest that supplementation of probiotics has significant effect on growth performance and certain haemato-biochemical parameters of broiler chickens as compared to antibiotic supplementation.

scholarly journals The Ameliorating Effects of Garlic (Allium sativum) against Lead (Pb) Intoxication on Body Weight, Dressing Percentages, Feed Consumption and Feed Conversion Ratio in Lead Induced Broiler Chickens

2014 ◽  
Vol 12 (1) ◽  
pp. 1-7 ◽  
Author(s):  
MA Hossain ◽  
M Mostofa ◽  
MN Alam ◽  
MR Sultana ◽  
MM Rahman
Keyword(s):  
Body Weight ◽  
Lead Acetate ◽  
Broiler Chickens ◽  
Allium Sativum ◽  
Live Weight ◽  
Conversion Ratio ◽  
Feed Conversion Ratio ◽  
Carcass Weight ◽  
Feed Conversion ◽  
Treatment Groups

Lead (Pb) has extensive commercial and industrial use despite of its recognized as health hazard. The therapeutic application of garlic (Allium sativum) was investigated for preventing the toxic effect of lead (Pd) in lead exposed chickens. 350 commercial broiler chickens were grouped into five such as T0, T1, T2, T3 and T4consisting of 70 birds each where T0 served as control. T1 was provided with lead acetate at 100mg/kg body weight, T2 had 100mg/kg lead acetate + 1% garlic supplement, T3 was fed with 100mg/kg lead acetate + 2% garlic supplement and T4 had 100mg/kg lead acetate + 4% garlic supplement for 42 days. Garlic was found to be capable of elimination of lead (Pb). Analysis of variance statistically revealed that significant (P<0.01) lower level of live weight (g), carcass weight (g) and eviscerated fresh carcass weight (%) were 2015.26±49.73, 1124.45±11.67 and 60.63±3.18, respectively in the chickens in group T1 at 42nd day of treatment in comparison to other groups. All garlic treatment groups satisfactorily increased live weight and carcass weight. Following the application of dietary garlic, mean values of live weight (g), carcass weight (g) and eviscerated fresh carcass weight (%) were significantly (P<0.01) increased at 2156.63±74.52, 1455.85±9.21 and 63.96±2.18 in group T3. Feed conversion ratio showed non-significant differences between different groups, but the most significant (P<0.01) FCR values were recorded in T3 among the treatment groups. It can be recommended from the present study that garlic might be played an active role to antagonize lead (Pb) toxicity.DOI: http://dx.doi.org/10.3329/bjvm.v12i1.20453 Bangl. J. Vet. Med. (2014). 12 (1): 1-7 

scholarly journals Local Stabilization of Hypoxia-Inducible Factor-1α Controls Intestinal Inflammation via Enhanced Gut Barrier Function and Immune Regulation

2021 ◽  
Vol 11 ◽  
Author(s):  
Young-In Kim ◽  
Eun-Je Yi ◽  
Young-Dae Kim ◽  
A Reum Lee ◽  
Jiwoung Chung ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Barrier Function ◽  
Intestinal Inflammation ◽  
Hypoxia Inducible Factor ◽  
Intestinal Epithelial ◽  
Intestinal Trefoil Factor ◽  
Gut Barrier Function ◽  
Tissue Healing ◽  
Inflammatory Bowel

Intestinal epithelial cells are adapted in mucosal hypoxia and hypoxia-inducible factors in these cells can fortify barrier integrity to support mucosal tissue healing. Here we investigated whether hypoxia-related pathways could be proposed as potential therapeutic targets for inflammatory bowel disease. We developed a novel hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor, CG-598 which stabilized HIF-1α in the gut tissue. Treatment of CG-598 did not affect extra-intestinal organs or cause any significant adverse effects such as erythropoiesis. In the experimental murine colitis model, CG-598 ameliorated intestinal inflammation with reduction of inflammatory lesions and pro-inflammatory cytokines. CG-598 treatment fortified barrier function by increasing the expression of intestinal trefoil factor, CD73, E-cadherin and mucin. Also, IL-10 and IL-22 were induced from lamina propria CD4+ T-cells. The effectiveness of CG-598 was comparable to other immunosuppressive therapeutics such as TNF-blockers or JAK inhibitors. These results suggest that CG-598 could be a promising therapeutic candidate to treat inflammatory bowel disease.

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