Necrotic enteritis (NE), caused by Clostridium perfringens (CP), is one of the most common of poultry diseases, causing huge economic losses to the poultry industry. This review provides an overview of the pathogenesis of NE in chickens and of the interaction of CP with the host immune system. The roles of management, nutrition, probiotics, and vaccination in reducing the incidence and severity of NE in poultry flocks are also discussed.

We 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.

Necrotic enteritis (NE) has become one of the most important diseases of modern global poultry production, with an estimated cost of around US$6 billion per annum in lost production and control strategies. The rise in prominence of NE is attributed to the prohibition of antibiotics as growth promoters (AGP) or the voluntary implementation of ‘drug-free’ broiler production programmes. Pathogenic strains of Clostridium perfringens are responsible for NE, with those expressing the NetB toxin a definitive cause in disease models. C. perfringens are normal inhabitants of the gastrointestinal tract (GIT) but these are typically non-pathogenic strains. When intestinal health is compromised, the prevailing conditions allow the establishment and proliferation of pathogenic, toxin-secreting strains of C. perfringens. The toxin(s) damages the intestinal epithelium and causes disease. Certain dietary-related factors are recognised as predisposing poultry to NE. This review will focus on the key initiators of NE and will outline the most appropriate strategies to counteract these predisposing factors and prevent NE. The continual push, globally, for poultry production programmes with less antibiotic use will sustain NE as an important and costly poultry disease that requires dietary intervention.

Resin acid composition (RAC) has previously been shown to inhibit the growth of the Gram-positive bacterial species Clostridium perfringens in vitro and to modulate the ileal microbiota of broiler chickens. The following trials examined the effect of RAC on broiler chickens in two experiments. In experiment 1, 1400 one-day-old Ross 308 broilers were divided into two coccidiostat treatments: chemical (CC) and ionophore (IC), which were further divided into two RAC dosages: 0 and 0.5 g/kg. All diets were supplemented with xylanase, β-glucanase and phytase feed enzymes. The birds were raised in a commercial-type environment without additional microbial challenge during the 42-day trial. RAC improved the body weight gain by 3.3% and feed conversion ratio by 5.7% with CC, and improved footpad lesion scores with IC but had no effect on the litter quality. Experiment 2 was a 35-day subclinical necrotic enteritis (NE) challenge trial with 510 male Ross 308 chickens. The dietary treatments included a non-challenged, non-supplemented control and four NE challenged treatments with dietary RAC supplementation at 0, 1, 2, and 3 g/kg. The birds were challenged with Eimeria maxima on day nine and C. perfringens on day 14. While RAC at 1 g/kg significantly increased bird weight gain during the challenge, it did not affect the microbial or short chain fatty acid (SCFA) profiles. In contrast, RAC at 3 g/kg reduced the abundance of the Lactobacillus group and tended to reduce the abundance of genus Bifidobacterium and the total numbers of eubacteria. These experiments suggest that dietary RAC at a moderate dose positively affected broiler performance. However, changes in caecal microbiota populations may not have influenced the observed performance effects of RAC.

Resin acids extracted from coniferous trees are known for their antimicrobial and antifungal effects. This trial investigated the effect of a natural resin acid-enriched composition (RAC) on the gastrointestinal microbiota and productive performance of broiler chicken. The results demonstrated that at or above 5 mg/l, RAC prevented the growth of a pure culture of Clostridium perfringens, a causative agent of necrotic enteritis in poultry. Next, the effects of RAC on the microbial community were studied in a fermentation model with both the microbial inoculum and substrate for the microbes isolated from the ileum of broiler chickens. RAC was included at 0, 0.1 and 1 g/kg digesta, and supplementation decreased the relative proportion of lactic acid and increased that of acetic acid produced during the fermentation in a dose-dependent manner. At 1 g/kg inclusion, RAC decreased the density of lactobacilli. The final part of the experiment investigated the influence of RAC on the performance and intestinal microbiota of necrotic enteritis (NE)-challenged broiler chickens. A wheat and soy -based diet was supplemented with RAC at 0, 0.5, 1 and 3 g/kg. The chickens were challenged with Eimeria maxima oocysts on day 11, and a pure culture of C. perfringens on day 14. On day 17, the final day of the trial, RAC inclusion at 1 and 3 g/kg of feed significantly increased body weight. At 3 g/kg RAC numerically decreased the daily mortality seen during the challenge period. In the ileum, RAC at 1 g/kg reduced the NE-associated peak of microbial lactic acid production. Overall, the data suggested that the dietary ingredient RAC has the potential to act as a performance-enhancer and microbial modulator in broiler chickens.

Necrotic enteritis (NE) caused by Clostridium spp. is an economically significant bacterial disease of poultry worldwide. Traditionally the disease has been prevented through feed supplementation with antibiotics sub-therapeutically as antimicrobial growth promoters (AGPs). However this practice has led to the emergence of resistant pathogenic microbes and drug residues, potentially threatening animal and public health. Therefore the marketing and incorporation of AGPs into poultry feed has been banned in Europe which has exacerbated the incidence of NE, bringing about huge economic losses to poultry farmers. Poultry researchers, exporters and consumers have emphasised AGP-free poultry rearing and have been searching for non-antibiotic and cost effective alternatives to control NE. Strategies suggested include vaccination, coccidiosis control, probiotics, competitive exclusion products, prebiotics, egg yolk immunoglobulins, bacteriophages (or phage gene products), organic acids, feed enzymes, plants and plants extracts/essential oils and nutritional changes.

There are many predisposing as well as virulence factors for NE induction and pathogenesis and more are expected to be discovered in the future. The ambiguous pathogenesis trend of the disease is still hindering the development of a potent active vaccine against NE. The choice of a single and fully effective approach is difficult. However, probiotics and specific egg yolk immunoglobulins (IgYs) alone or in combination could serve as promising strategies for controlling NE in broilers in the absence of AGPs.

Sub-clinical necrotic enteritis (NE) is a major economic cost to the broiler production industry due to poor growth and feed conversion efficiency of broiler chicken flocks, higher condemnation of livers or rarely the whole carcasses at the slaughter house and an increased risk of microbial contamination of poultry meat. Sub-clinical NE is a multifactorial disease although Clostridium perfringens plays a major role in its pathogenesis. Its diagnosis and confirmation are quite different from those of general infectious diseases. Disease confirmation is from the presence of necrotic or ulcerative lesions on the small intestinal mucosa with identifiable aggregates of pathogenic C. perfringens. C. perfringens numbers in the small intestinal digesta or the mucosal scrapings are not correlated with disease severity, whereas counts above 106 cfu/g in the caecal contents indicate an increased probability of NE-specific gut lesions. Not only does the presence and counts of C. perfringens strains capable of producing related toxins affect the incidence of the disease but also a number of predisposing factors are important in the aetiology of NE. The major factors that predispose growing chickens to sub-clinical NE are diet variables, diseases that cause mucosal damage of the intestine and environmental factors that either alter the development of gut associated lymphoid tissue or change litter quality within the production house. Dietary variables may be a major cause of variation in sub-clinical NE in commercial broiler production; differences in polysaccharides, lipids, protein sources, protein digestibility and the presence of antinutritive factors have been identified as variables affecting the incidence of the disease.

The Clostridium-related poultry disease, necrotic enteritis (NE), causes substantial economic losses on a global scale. In the present study, a mixture of two plant-derived phytonutrients, Capsicum oleoresin and turmeric oleoresin (XT), was evaluated for its effects on local and systemic immune responses using a co-infection model of experimental NE in commercial broilers. Chickens were fed from hatch with a diet supplemented with XT, or with a non-supplemented control diet, and either uninfected or orally challenged with virulent Eimeria maxima oocysts at 14 d and Clostridium perfringens at 18 d of age. Parameters of protective immunity were as follows: (1) body weight; (2) gut lesions; (3) serum levels of C. perfringens α-toxin and NE B-like (NetB) toxin; (4) serum levels of antibodies to α-toxin and NetB toxin; (5) levels of gene transcripts encoding pro-inflammatory cytokines and chemokines in the intestine and spleen. Infected chickens fed the XT-supplemented diet had increased body weight and reduced gut lesion scores compared with infected birds given the non-supplemented diet. The XT-fed group also displayed decreased serum α-toxin levels and reduced intestinal IL-8, lipopolysaccharide-induced TNF-α factor (LITAF), IL-17A and IL-17F mRNA levels, while cytokine/chemokine levels in splenocytes increased in the XT-fed group, compared with the animals fed the control diet. In conclusion, the present study documents the molecular and cellular immune changes following dietary supplementation with extracts of Capsicum and turmeric that may be relevant to protective immunity against avian NE.

Necrotic enteritis is a disease in poultry that can have a high economic and animal welfare cost, and has become increasingly prevalent in the European Union due to factors such as the removal of antibiotic growth promoters and the requirement to exclude animal by-products from diet formulations. Estimates of the prevalence of necrotic enteritis vary widely (1–40%) as does the cost of the disease, and the subclinical form may be the most important manifestation of the disease as this is likely to go undetected and hence untreated. An outbreak of necrotic enteritis is primarily associated with rapid proliferation of the anaerobic bacterium, Clostridium perfringens type A or C, leading to gaseous extension of the small intestine, the production of one or more exotoxins, and enteric toxicosis. The molecular progression of the disease is quite complex and at the bacterial level involves quorum sensing, toxin production and secretion, and interactions of the pathogen with the innate immune system of the chicken. Intestinal cell permeation by the toxin activates a series of intracellular pathways including protein kinase cascades, and ultimately results in cell death. The precise molecular signals that set off this cascade are still unclear. The various predisposing environmental, health and dietary factors that modify the gut environment and promote colonisation with C. perfringens, are discussed. With such a multi-factorial disease, a working and reproducible experimental model with which to study bacterial/host and dietary/host interactions is an essential tool in the search for appropriate control or management strategies for the poultry industry.

Well known as the cause of necrotic enteritis, C. perfringens (CP) is now recognized as causing a spectrum of effects including subclinical infection, mild disease with focal intestinal necrosis, diarrhoeal illness and liver disease, as well as the classic form of acute fulminant necrotizing enteritis. The mild and subclinical forms of infection appear to be widespread, and, possibly increasing in incidence. Furthermore, bacterial enteritis is increasingly being recognized less as an invasion by pathogenic organisms per se and more as an expression of the normal process by which the intestinal bacterial population changes overtime in response to changes in the intestinal environment. Such shifts in enteric bacterial populations have been referred to as dysbacteriosis. Management of the microbial ecology of the intestinal tract is therefore an important element of preventing disease, enhancing performance, and preventing foodborne illness. Diagnosis of emerging forms of bacterial enteritis including CP infection can be challenging and involves a comprehensive analysis of flock history and condemnation records, clinical signs, gross and histopathology, bacterial culture and empirical response to treatment, augmented by molecular techniques where available. Control measures are at present based on extensions of validated approaches to the control of the classical form of the disease: managing known risk factors for necrotic enteritis (coccidiosis, diet and litter quality) and the use of approved antimicrobial agents with proven efficacy against CP.

Studies with germ-free chicks and antimicrobial compounds have indicated the significance of the interaction between host nutrition and the intestinal microflora. This interaction has suddenly leapt to prominence as a result of the decision of the European Union to remove several antibacterial agents from use in animal feed. A consequence of this decision has been a loosening of some of the constraints on intestinal bacterial growth rates which will benefit from the use of slowly digested ingredients, because undigested feed is a potential substrate for bacterial fermentation. The use of poorly digestible ingredients runs the risk not only of poor performance, which has always been the case, but now there is an additional danger from bacterial overgrowth and subsequent disease/intestinal disorders. Variations in the nutritional quality of the ingredients are therefore of increased relevance, and any measures that reduce such variations are likely to be of benefit. As a result, the use of enzymes, which are known to reduce variations in the performance of birds fed on barley-, wheat- and maize-based diets, will need to be revisited, particularly with reference to correct dosage. In the past the use of antibiotics effectively reduced the need to consider enzyme use and dose. Coccidiosis control is also of great interest because of its association with necrotic enteritis. Prevention of coccidiosis and limitation of the damage to the intestines associated with this disease is of paramount importance if necrotic enteritis is subsequently to be avoided. As a result, the use of coccidiostats for direct control and betaine and other pronutrients for amelioration of the symptoms is receiving greater attention. Ultimately it is hoped that nutritional control will lead to microbiological control, allowing for more consistent production responses in the absence of antibiotics.