scholarly journals Dietary Ellagic Acid Ameliorated Clostridium Perfringens-Induced Subclinical Necrotizing Enteritis In Broilers Via Regulating Inflammation Signaling Pathways And Cecal Microbiota to Inhibit Intestinal Barrier Damage

2021 ◽  
Author(s):  
Yu Tang ◽  
Xinyue Zhang ◽  
Yanan Wang ◽  
Yongpeng Guo ◽  
Peiqi Zhu ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Signaling Pathways ◽  
Clostridium Perfringens ◽  
Relative Abundance ◽  
Ellagic Acid ◽  
Intestinal Barrier ◽  
Production Performance ◽  
Intestinal Damage ◽  
Crypt Depth ◽  
Cecal Microbiota

Abstract Background: Subclinical necrotizing enteritis (SNE) is a common intestinal disease caused by Clostridium perfringens in broilers, which cause chronic intestinal damage, affect the digestion and absorption of nutrients, and reduce production performance. Ellagic acid (EA) has been reported to have antioxidant and anti-inflammatory properties in many aspects. This study was conducted to evaluate the effect and mechanism of EA in relieving subclinical necrotizing enteritis in broilers induced by C. perfringens. Results: C. perfringens challenge decreased body weight (BW), average daily gain (ADG); jejunal villi height/crypt depth (V/C); the activity of catalase (CAT), and the mRNA expression of zonula occludens 1 (ZO-1) in jejunum mucosa of broilers. While it increased feed conversion ratios (FCR); jejunal crypt depth (CD); activities of myeloperoxidase (MPO) and diamine oxidase (DAO), as well as concentrations of interleukin 6 (IL-6), C-reactive protein (CRP), and procalcitonin (PCT) in serum; activities of inducible nitric oxide synthase (iNOs) and lysozyme (LZM), the concentration of malondialdehyde (MDA), and the mRNA expression of claudin-2, TNF-α, IL-1β, TLR4, TLR2, NF-κB, JAK3, STAT6 and iNOs in jejunum mucosa of broilers. Dietary EA supplement relieved these adverse effects, and heightened jejunal villi height (VH); the concentration of D-xylose in plasma; activities of superoxide dismutase (SOD), and the mRNA expression of occludin in jejunum mucosa of broilers. The alpha diversity of cecal microbiota exhibited dietary EA supplement increased observed species and Shannon index. C. perfringens challenge increased the relative abundance of Firmicutes and decreased the relative abundance of Desulfobacterota. Similarly, EA increased relative abundance of Firmicutes. LEfSe analysis showed that C. perfringens challenge harmed the cecal microbiota of broiler chickens, dietary EA supplementation led to a small beneficial effect, while the simultaneous effect of them seems to stimulate the immune function of broilers and made broilers possess a better cecal microbiota. Conclusions: Dietary EA ameliorated C. perfringens-induced SNE in broilers via regulating jejunal inflammation signaling pathways TLR/NF-κB and JAK3/STAT6, relieving jejunal oxidative stress, and balancing cecal microbiota to inhibit intestinal barrier damage, prevent systemic inflammatory response, and improve nutrient absorption capacity, finally protect and enhance growth performance of broilers.

Bisdemethoxycurcumin Attenuates Lipopolysaccharide-Induced Intestinal Damage through Improving Barrier Integrity, Suppressing Inflammation, and Modulating Gut Microbiota in Broilers

2021 ◽  
Author(s):  
Jingfei Zhang ◽  
Yuxiang Yang ◽  
Hongli Han ◽  
Lili Zhang ◽  
Tian Wang
Keyword(s):  
Tight Junction ◽  
Mrna Expression ◽  
Relative Abundance ◽  
Inflammatory Mediators ◽  
Broiler Chickens ◽  
Basal Diet ◽  
Intestinal Morphology ◽  
Intestinal Damage ◽  
Lps Challenge ◽  
Cecal Microbiota

Abstract Bisdemethoxycurcumin has good antioxidant and anti-inflammatory effects and has been widely used as food and feed supplements in the form of curcuminoids. However, the beneficial effect of individual bisdemethoxycurcumin on preventing lipopolysaccharide (LPS)-induced inflamed intestinal damage is unclear. The present study aimed to investigate whether dietary bisdemethoxycurcumin supplementation could attenuate LPS-induced intestinal damage and alteration of cecal microbiota in broiler chickens. In total, 320 one-day-old male Arbor Acres broiler chickens with a similar weight were randomly divided in four treatments. The treatments were designed as a 2 × 2 factorial arrangement: basal diet (CON); 150 mg/kg bisdemethoxycurcumin diet (BUR); LPS challenge + basal diet (LPS); LPS challenge + 150 mg/kg bisdemethoxycurcumin diet (L-BUR). Results showed that dietary bisdemethoxycurcumin supplementation attenuated the LPS-induced decrease of average daily feed intake. LPS challenge compromised the intestinal morphology and disrupted the intestinal tight junction barrier. Dietary bisdemethoxycurcumin supplementation significantly increased villus length:crypt depth ratio and up-regulated the mRNA expression of intestinal tight junction proteins. Moreover, a remarkably reduced mRNA expression of inflammatory mediators was observed following bisdemethoxycurcumin supplementation. The cecal microbiota analysis showed that bisdemethoxycurcumin supplementation increased the relative abundance of the genus Faecalibacterium while decreased the relative abundance of the genera Bacteroides and Subdoligranulum. In conclusion, dietary bisdemethoxycurcumin supplementation could counteract LPS-induced inflamed intestinal damage in broiler chickens by improving intestinal morphology, maintaining intestinal tight junction, down-regulating pro-inflammatory mediators, and restoring cecal microbiota.

scholarly journals Dietary l-arginine inhibits intestinal Clostridium perfringens colonisation and attenuates intestinal mucosal injury in broiler chickens

2017 ◽  
Vol 118 (5) ◽  
pp. 321-332 ◽  
Author(s):  
Beibei Zhang ◽  
Zengpeng Lv ◽  
Huixian Li ◽  
Shuangshuang Guo ◽  
Dan Liu ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Clostridium Perfringens ◽  
Broiler Chickens ◽  
Mucosal Injury ◽  
Intestinal Damage ◽  
Intestinal Mucosal Injury ◽  
Ifn Γ ◽  
Arginine Supplementation

AbstractWe investigated the effects of dietary l-arginine level and feeding duration on the intestinal damage of broilers induced by Clostridium perfringens (CP) in vivo, and the antimicrobial effect of its metabolite nitric oxide (NO) in vitro. The in vivo experiment was designed as a factorial arrangement of three dietary treatments×two challenge statuses. Broilers were fed a basal diet (CON) or a high-arginine diet (ARG) containing 1·87 % l-arginine, or CON for the first 8 d and ARG from days 9 to 28 (CON/ARG). Birds were co-infected with or without Eimeria and CP (EM/CP). EM/CP challenge led to intestinal injury, as evidenced by lower plasma d-xylose concentration (P<0·01), higher paracellular permeability in the ileum (P<0·05) and higher numbers of Escherichia coli (P<0·05) and CP (P<0·001) in caecal digesta; however, this situation could be alleviated by l-arginine supplementation (P<0·05). The intestinal claudin-1 and occludin mRNA expression levels were decreased (P<0·05) following EM/CP challenge; this was reversed by l-arginine supplementation (P<0·05). Moreover, EM/CP challenge up-regulated (P<0·05) claudin-2, interferon-γ (IFN-γ), toll-like receptor 2 and nucleotide-binding oligomerisation domain 1 (NOD1) mRNA expression, and l-arginine supplementation elevated (P<0·05) IFN-γ, IL-10 and NOD1 mRNA expression. In vitro study showed that NO had bacteriostatic activity against CP (P<0·001). In conclusion, l-arginine supplementation could inhibit CP overgrowth and alleviate intestinal mucosal injury by modulating innate immune responses, enhancing barrier function and producing NO.

scholarly journals Anemonin improves intestinal barrier restoration and influences TGF-β1 and EGFR signaling pathways in LPS-challenged piglets

2016 ◽  
Vol 22 (5) ◽  
pp. 344-352 ◽  
Author(s):  
Kan Xiao ◽  
Shu Ting Cao ◽  
Le Fei Jiao ◽  
Fang Hui Lin ◽  
Li Wang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Mrna Expression ◽  
Signaling Pathways ◽  
Intestinal Barrier ◽  
Basal Diet ◽  
Jejunal Mucosa ◽  
Egfr Signaling ◽  
Epidermal Growth ◽  
Tgf Β1

The present study was aimed at investigating whether dietary anemonin could alleviate LPS-induced intestinal injury and improve intestinal barrier restoration in a piglet model. Eighteen 35-d-old pigs were randomly assigned to three treatment groups (control, LPS and LPS+anemonin). The control and LPS groups were fed a basal diet, and the LPS + anemonin group received the basal diet + 100 mg anemonin/kg diet. After 21 d of feeding, the LPS- and anemonin-treated piglets received i.p. administration of LPS; the control group received saline. At 4 h post-injection, jejunum samples were collected. The results showed that supplemental anemonin increased villus height and transepithelial electrical resistance, and decreased crypt depth and paracellular flux of dextran (4 kDa) compared with the LPS group. Moreover, anemonin increased tight junction claudin-1, occludin and ZO-1 expression in the jejunal mucosa, compared with LPS group. Anemonin also decreased TNF-α, IL-6, IL-8 and IL-1β mRNA expression. Supplementation with anemonin also increased TGF-β1 mRNA and protein expression, Smad4 and Smad7 mRNA expressions, and epidermal growth factor and epidermal growth factor receptor (EGFR) mRNA expression in the jejunal mucosa. These findings suggest that dietary anemonin attenuates LPS-induced intestinal injury by improving mucosa restoration, alleviating intestinal inflammation and influencing TGF-β1 canonical Smads and EGFR signaling pathways.

scholarly journals Clostridium butyricum Supplement Can Ameliorate the Intestinal Barrier Roles in Broiler Chickens Experimentally Infected With Clostridium perfringens

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiao Xu ◽  
Shunli Yang ◽  
Joshua Seun Olajide ◽  
Zigang Qu ◽  
Zhenxing Gong ◽  
...  
Keyword(s):  
Growth Performance ◽  
Clostridium Perfringens ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Infected Group ◽  
Clostridium Butyricum ◽  
Intestinal Morphology ◽  
Daily Weight Gain ◽  
Intestinal Damage ◽  
Intestinal Integrity

Necrotic enteritis (NE), caused by Clostridium perfringens, is an economically important disease in the broiler. Among normal flora in the broiler intestinal region, Clostridium butyricum has been identified as a probiotic agent that reduces the susceptibility of broilers to C. perfringens. However, the effects of C. butyricum supplement on broiler intestinal integrity during NE are largely unknown. In this study, we investigated the effects of C. butyricum on the growth performance, intestinal morphology and barrier function, and the functions of immune-related cytokines under NE in broilers. Chickens were divided into five groups: control group (NC), supplement C. butyricum only group (CB), NE-infected group (PC), supplement C. butyricum from Day 14 (NECB1) to Day 22 NE-infected group, and supplement C. butyricum from Day 1 (NECB2) to Day 22 NE-infected group. The results showed that there were significantly decreased average daily weight gain and increased feed conversion rate in the infected group (PC) compared with the C. butyricum-supplemented groups (NECB1 and NECB2) through the diet. Histopathological observation on the Hematoxylin–Eosin staining avian small intestine sections revealed that supplementation of C. butyricum (NECB1 and NECB2) could increase the intestinal villus height/crypt depth and lessen the intestinal damage under NE. ELISA and Limulus test showed that broilers infected with NE (PC) had higher serum IgA and lipopolysaccharide content; however, after C. butyricum supplementation (NECB1 and NECB2), they returned to a normal level. Furthermore, real-time PCR and Western blot results indicated that compared with PC, supplementing C. butyricum (NECB1 and NECB2) could initialize the expressions of genes related to the intestinal barrier-associated molecules (such as CLDN-1, CLDN-3, OCLN, MUC2, ZO-1, and CLDN5), cytokines (such as IL-10, IL-6, and TGFB1), and C. perfringens plc gene expression. Moreover, the results detected by the Ussing chamber suggested that C. butyricum (NECB1 and NECB2) could amend the decrease in conductivity value and short-circuit current value caused by NE. In addition, NECB2 significantly reduced the upregulation of fluorescein isothiocyanate–dextran flux caused by the NE disease. In conclusion, these findings suggest that dietary supplementation of C. butyricum in broilers with NE improved chicken growth performance, intestinal integrity and barrier function, and immunological status. Notably, no statistical difference was observed with the addition of C. butyricum on day 1 or day 14.

scholarly journals Glycerol Monolaurate Ameliorated Intestinal Barrier and Immunity in Broilers by Regulating Intestinal Inflammation, Antioxidant Balance, and Intestinal Microbiota

2021 ◽  
Vol 12 ◽  
Author(s):  
Linglian Kong ◽  
Zhenhua Wang ◽  
Chuanpi Xiao ◽  
Qidong Zhu ◽  
Zhigang Song
Keyword(s):  
Intestinal Microbiota ◽  
Intestinal Barrier ◽  
Intestinal Morphology ◽  
Interleukin 1Β ◽  
Average Weight ◽  
Broiler Chicks ◽  
Crypt Depth ◽  
Glycerol Monolaurate ◽  
Cecal Microbiota ◽  
The Impact

This study was conducted to investigate the impact of glycerol monolaurate (GML) on performance, immunity, intestinal barrier, and cecal microbiota in broiler chicks. A total of 360 one-day-old broilers (Arbor Acres) with an average weight of 45.7 g were randomly allocated to five dietary groups as follows: basal diet and basal diets complemented with 300, 600, 900, or 1200 mg/kg GML. Samples were collected at 7 and 14 days of age. Results revealed that feed intake increased (P &lt; 0.05) after 900 and 1200 mg/kg GML were administered during the entire 14-day experiment period. Dietary GML decreased (P &lt; 0.05) crypt depth and increased the villus height-to-crypt depth ratio of the jejunum. In the serum and jejunum, supplementation with more than 600 mg/kg GML reduced (P &lt; 0.05) interleukin-1β, tumor necrosis factor-α, and malondialdehyde levels and increased (P &lt; 0.05) the levels of immunoglobulin G, jejunal mucin 2, total antioxidant capacity, and total superoxide dismutase. GML down-regulate (P &lt; 0.05) jejunal interleukin-1β and interferon-γ expression and increased (P &lt; 0.05) the mRNA level of zonula occludens 1 and occludin. A reduced (P &lt; 0.05) expression of toll-like receptor 4 and nuclear factor kappa-B was shown in GML-treated groups. In addition, GML modulated the composition of the cecal microbiota of the broilers, improved (P &lt; 0.05) microbial diversity, and increased (P &lt; 0.05) the abundance of butyrate-producing bacteria. Spearman’s correlation analysis revealed that the genera Barnesiella, Coprobacter, Lachnospiraceae, Faecalibacterium, Bacteroides, Odoriacter, and Parabacteroides were related to inflammation and intestinal integrity. In conclusion, GML ameliorated intestinal morphology and barrier function in broiler chicks probably by regulating intestinal immune and antioxidant balance, as well as intestinal microbiota.

scholarly journals Effect of Dietary Clostridium butyricum Supplementation on Growth Performance, Intestinal Barrier Function, Immune Function, and Microbiota Diversity of Pekin Ducks

Animals ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 2514
Author(s):  
Yanhan Liu ◽  
Cun Liu ◽  
Keying An ◽  
Xiaowei Gong ◽  
Zhaofei Xia
Keyword(s):  
Growth Performance ◽  
Mrna Expression ◽  
Intestinal Microbiota ◽  
Relative Abundance ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Expression Levels ◽  
Pekin Ducks ◽  
Mrna Expression Levels

Clostridium butyricum (C. butyricum) is increasingly being used to test the promotion of the gut health of animals. However, the modes of action for such applications for waterfowl remain unclear. Thus, we investigated whether or not intestinal barrier function, immune-related gene expression, and the diversity of the intestinal microbiota in Pekin ducks varied under C. butyricum supplementation. A total of 500 ducks were randomly assigned into five treatments supplemented with basal diets containing: either 0 (group Control), 200 (group CB200), 400 (group CB400) and 600 (group CB600) mg/kg C. butyricum or 150 mg/kg aureomycin (group A150) for 42 days. In comparison with the control group, C. butyricum supplementation enhanced the growth performance and intestinal villus height of Pekin ducks at 42 d. Serum immune indexes and fecal short-chain fatty acids (SCFAs) were all improved at both 21 d and 42 d after C. butyricum addition. The mRNA expression levels of Mucin2, Zonula occludens-1 (ZO-1), Caudin-3, and Occludin increased at 21 d and 42 d and the mRNA expression levels of IL-4 and IL-10 only increased at 42 d after C. butyricum addition. Dietary C. butyricum also resulted in an increase in the number of diversities of operational taxonomic units (OTUs), and an increase in the α-diversity of intestinal microbiota. The addition of C. butyricum altered the composition of the intestinal microbiota from 21 d to 42 d. The relative abundance of Firmicutes and Bacteroidetes showed little changes among groups; however, the relative abundance of Firmicutes/Bacteroidetes were found to have been significantly different between the 21 d and 42 d. C. butyricum administration improved the intestinal health of Pekin ducks by increasing the diversity of intestinal microbiota, enhancing the SCFAs contents, and strengthening the intestinal barrier function and immune systems. The optimal dietary supplementation dosage was recommended as 400 mg/kg in the diet.

scholarly journals Glycerol monolaurate ameliorated intestinal barrier and immunity in broilers by regulating intestinal inflammation, antioxidant balance, and intestinal microbiota

2021 ◽  
Author(s):  
Linglian Kong ◽  
Zhenhua Wang ◽  
Chuanpi Xiao ◽  
Qidong Zhu ◽  
Zhi Gang Song
Keyword(s):  
Intestinal Microbiota ◽  
Intestinal Inflammation ◽  
Intestinal Barrier ◽  
Intestinal Morphology ◽  
Interleukin 1Β ◽  
Broiler Chicks ◽  
Crypt Depth ◽  
Glycerol Monolaurate ◽  
Cecal Microbiota ◽  
The Impact

Extensive interactions occur between a poultry host and its gut microbiome. Glycerol monolaurate (GML) possesses a large range of antimicrobial and immunoregulatory properties. This study was conducted to investigate the impact of different doses of GML (basal diets complemented with 0, 300, 600, 900, or 1200 mg/kg GML) on growth performance, intestinal barrier, and cecal microbiota in broiler chicks. Results revealed that feed intake increased after 900 and 1200 mg/kg GML were administered during the entire 14-day experiment period. Dietary GML decreased crypt depth and increased the villus height-to-crypt depth ratio of the jejunum. In the serum and jejunum, supplementation with more than 600 mg/kg GML reduced interleukin-1β, tumor necrosis factor-α, and malondialdehyde levels and increased the levels of immunoglobulin G, jejunal mucin 2, total antioxidant capacity, and total superoxide dismutase. GML down-regulated jejunal interleukin-1β and interferon-γ expression and increased the mRNA level of zonula occludens 1 and occludin. A reduced expression of toll-like receptor 4 and a tendency of down-regulated nuclear factor kappa-B was shown in GML-treated groups. In addition, GML modulated the composition of the cecal microbiota of the broilers, improved microbial diversity, and increased the abundance of butyrate-producing bacteria. Spearman's correlation analysis revealed that the genera Barnesiella, Coprobacter, Lachnospiraceae, Faecalibacterium, Bacteroides, Odoriacter, and Parabacteroides were related to inflammation and intestinal integrity. In conclusion, GML ameliorated intestinal morphology and barrier function in broiler chicks probably by regulating intestinal immune and antioxidant balance, as well as intestinal microbiota.

scholarly journals Comprehensive analysis of lncRNA and mRNA based on expression microarray profiling reveals different characteristics of osteoarthritis between Tibetan and Han patients

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Junming Luo ◽  
Xiaoqin Luo ◽  
Zhili Duan ◽  
Wenbin Bai ◽  
Xiaoming Che ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Signaling Pathways ◽  
Critical Role ◽  
Joint Disease ◽  
Biological Processes ◽  
Expression Microarray ◽  
Chinese Han ◽  
Microarray Profiling ◽  
Trans Regulation ◽  
Mrna Expression Profiling

Abstract Background Osteoarthritis (OA) is thought to be the most prevalent chronic joint disease, especially in Tibet of China. Here, we aimed to explore the integrative lncRNA and mRNA landscape between the OA patients of Tibet and Han. Methods The lncRNA and mRNA expression microarray profiling was performed by SurePrint G3 Human Gene Expression 8x60K v2 Microarray in articular cartilage samples from OA patients of Han nationality and Tibetans, followed by GO, KEGG, and trans-regulation and cis-regulation analysis of lncRNA and mRNA. Results We found a total of 117 lncRNAs and 297 mRNAs differently expressed in the cartilage tissues of Tibetans (n = 5) comparing with those of Chinese Han (n = 3), in which 49 lncRNAs and 158 mRNAs were upregulated, and 68 lncRNAs and 139 mRNAs were downregulated. GO and KEGG analysis showed that several unreported biological processes and signaling pathways were particularly identified. LncRNA-mRNA co-expression analysis revealed a remarkable lncRNA-mRNA relationship, in which OTOA may play a critical role in the different mechanisms of the OA progression between Tibetans and Chinese Han. Conclusion This study identified different lncRNA/mRNA expression profiling between OA patients of Tibetans and Han, which were involved in many characteristic biological processes and signaling pathways.

scholarly journals Cystine reduces tight junction permeability and intestinal inflammation induced by oxidative stress in Caco-2 cells

Amino Acids ◽  
2021 ◽  
Author(s):  
Tatsuya Hasegawa ◽  
Ami Mizugaki ◽  
Yoshiko Inoue ◽  
Hiroyuki Kato ◽  
Hitoshi Murakami
Keyword(s):  
Oxidative Stress ◽  
Tight Junction ◽  
Mrna Expression ◽  
Inflammatory Cytokines ◽  
Inflammatory Responses ◽  
Intestinal Barrier ◽  
Barrier Dysfunction ◽  
Whole Cells ◽  
Intestinal Barrier Dysfunction ◽  
Pro Inflammatory Cytokines

AbstractIntestinal oxidative stress produces pro-inflammatory cytokines, which increase tight junction (TJ) permeability, leading to intestinal and systemic inflammation. Cystine (Cys2) is a substrate of glutathione (GSH) and inhibits inflammation, however, it is unclear whether Cys2 locally improves intestinal barrier dysfunction. Thus, we investigated the local effects of Cys2 on oxidative stress-induced TJ permeability and intestinal inflammatory responses. Caco-2 cells were cultured in a Cys2-supplemented medium for 24 h and then treated with H2O2 for 2 h. We assessed TJ permeability by measuring transepithelial electrical resistance and the paracellular flux of fluorescein isothiocyanate–dextran 4 kDa. We measured the concentration of Cys2 and GSH after Cys2 pretreatment. The mRNA expression of pro-inflammatory cytokines was assessed. In addition, the levels of TJ proteins were assessed by measuring the expression of TJ proteins in the whole cells and the ratio of TJ proteins in the detergent-insoluble fractions to soluble fractions (IS/S ratio). Cys2 treatment reduced H2O2-induced TJ permeability. Cys2 did not change the expression of TJ proteins in the whole cells, however, suppressed the IS/S ratio of claudin-4. Intercellular levels of Cys2 and GSH significantly increased in cells treated with Cys2. Cys2 treatment suppressed the mRNA expression of pro-inflammatory cytokines, and the mRNA levels were significantly correlated with TJ permeability. In conclusion, Cys2 treatment locally reduced oxidative stress-induced intestinal barrier dysfunction possively due to the mitigation of claudin-4 dislocalization. Furthermore, the effect of Cys2 on the improvement of intestinal barrier function is related to the local suppression of oxidative stress-induced pro-inflammatory responses.

scholarly journals Effects of Clostridium perfringens Beta-Toxin on the Rabbit Small Intestine and Colon

2008 ◽  
Vol 76 (10) ◽  
pp. 4396-4404 ◽  
Author(s):  
Jorge E. Vidal ◽  
Bruce A. McClane ◽  
Juliann Saputo ◽  
Jaquelyn Parker ◽  
Francisco A. Uzal
Keyword(s):  
Small Intestine ◽  
Clostridium Perfringens ◽  
Time Course ◽  
Defense Mechanism ◽  
Intestinal Damage ◽  
Loop Model ◽  
Type B ◽  
Ileal Loop ◽  
Type C ◽  
Beta Toxin

ABSTRACT Clostridium perfringens type B and type C isolates, which produce beta-toxin (CPB), cause fatal diseases originating in the intestines of humans or livestock. Our previous studies demonstrated that CPB is necessary for type C isolate CN3685 to cause bloody necrotic enteritis in a rabbit ileal loop model and also showed that purified CPB, in the presence of trypsin inhibitor (TI), can reproduce type C pathology in rabbit ileal loops. We report here a more complete characterization of the effects of purified CPB in the rabbit small and large intestines. One microgram of purified CPB, in the presence of TI, was found to be sufficient to cause significant accumulation of hemorrhagic luminal fluid in duodenal, jejunal, or ileal loops treated for 6 h with purified CPB, while no damage was observed in corresponding loops receiving CPB (no TI) or TI alone. In contrast to the CPB sensitivity of the small intestine, the colon was not affected by 6 h of treatment with even 90 μg of purified CPB whether or not TI was present. Time course studies showed that purified CPB begins to induce small intestinal damage within 1 h, at which time the duodenum is less damaged than the jejunum or ileum. These observations help to explain why type B and C infections primarily involve the small intestine, establish CPB as a very potent and fast-acting toxin in the small intestines, and confirm a key role for intestinal trypsin as an innate intestinal defense mechanism against CPB-producing C. perfringens isolates.

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