RESUMO
Antimicrobial restrictions prompted the search for cost and biologically effective alternatives to replace antimicrobial growth promoters (AGPs) in food-producing animals. In addition, the efficacy of this alternatives needs to be contrasted in field/commercial trials under different challenge conditions. However only a few studies describing the impact of tannins or others AGP-alternatives in commercial poultry production conditions are actually available. The aim of the present work is to study how the inclusion of a blend of chestnut and quebracho tannins can affect broiler productive performance and health under commercial conditions. Three experiments with different approaches were conducted: (1) a trial comparing the effects of both additives (tannins vs AGP) on different commercial farms at the same time; (2) the follow-up of one farm during an entire productive year; and (3) an experimental trial using a C. perfringens challenge model in broiler chickens. Although productive results from field trials were similar among treatments, evaluations of gut health indicators showed improvements in the tannins treated flocks. Frequency and severity of intestinal gross lesions were reduced in jejunum (42% vs 23%; p<0.05-1.37 vs. 0.73; p<0.01, respectively) and ileum (25% vs. 10%; p<0.0.5-1.05 vs. 0.58; p<0.01) in tannins treated birds. Results from 16S studies, show that cecal microbiota diversity was not differentially affected by AGPs or tannins, but changes in the relative abundance of certain taxa were described, including Lactobacillus and Bifidobacterium groups. Results from experimental C. perfringens necrotic enteritis showed that tannins treated birds had reduced incidence of gross lesions in jejunum (43.75 vs. 74.19%; p<0.01) and ileum (18.75% vs. 45.16%; p<0.05) compared with control. These results suggest that AGPs can be replaced by tannins feed additives, and contribute in the implementation of antimicrobial-free programs in broilers without affecting health or performance.
Assuntos
TaninosRESUMO
Gut microbiota and its relationship to animal health and productivity in commercial broiler chickens has been difficult to establish due to high variability between flocks, which derives from plenty of environmental, nutritional, and host factors that influence the load of commensal and pathogenic microbes surrounding birds during their growth cycle in the farms. Chicken gut microbiota plays a key role in the maintenance of intestinal health through its ability to modulate host physiological functions required to maintain intestinal homeostasis, mainly through competitive exclusion of detrimental microorganisms and pathogens, preventing colonization and therefore decreasing the expense of energy that birds normally invest in keeping the immune system active against these pathogens. Therefore, a "healthy" intestinal microbiota implies energy saving for the host which translates into an improvement in productive performance of the birds. This review compiles information about the main factors that shape the process of gut microbiota acquisition and maturation, their interactions with chicken immune homeostasis, and the outcome of these interactions on intestinal health and productivity.
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In this study, we found mcr-1.1 and mcr-1.5 genes carried by IncI2 plasmids in a subset of Escherichia coli isolates recovered from commercial broiler farms in Argentina. The comparative analysis of the sequences of these plasmids with those described in human clinical isolates suggests that this replicon-type is one of the main mcr-disseminator sources in Argentina.
Assuntos
Portador Sadio/veterinária , Galinhas , Infecções por Escherichia coli/veterinária , Proteínas de Escherichia coli/genética , Escherichia coli/genética , Plasmídeos/análise , Animais , Argentina , Portador Sadio/microbiologia , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/microbiologia , Genótipo , Análise de Sequência de DNARESUMO
The use of antimicrobial growth promoters (AGPs) in sub-therapeutic doses for long periods promotes the selection of resistant microorganisms and the subsequent risk of spreading this resistance to the human population and the environment. Global concern about antimicrobial resistance development and transference of resistance genes from animal to human has been rising. The goal of our research was to evaluate the susceptibility pattern to different classes of antimicrobials of colistin-resistant Escherichia coli from poultry production systems that use AGPs, and characterize the resistance determinants associated to transferable platforms. E. coli strains (n = 41) were obtained from fecal samples collected from typical Argentine commercial broiler farms and susceptibility for 23 antimicrobials, relevant for human or veterinary medicine, was determined. Isolates were tested by PCR for the presence of mcr-1, extended spectrum ß-lactamase encoding genes and plasmid-mediated quinolone resistance (PMQR) coding genes. Conjugation and susceptibility patterns of the transconjugant studies were performed. ERIC-PCR and REP-PCR analysis showed a high diversity of the isolates. Resistance to several antimicrobials was determined and all colistin-resistant isolates harbored the mcr-1 gene. CTX-M-2 cefotaximase was the main mechanism responsible for third generation cephalosporins resistance, and PMQR determinants were also identified. In addition, co-transference of the qnrB determinant on the mcr-1-positive transconjugants was corroborated, which suggests that these resistance genes are likely to be located in the same plasmid. In this work a wide range of antimicrobial resistance mechanisms were identified in E. coli strains isolated from the environment of healthy chickens highlighting the risk of antimicrobial abuse/misuse in animals under intensive production systems and its consequences for public health.
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The Estuary of Bahía Blanca (EBB), Argentina, is an important wetland under intense sewage pollution. We investigated the occurrence of Clostridium perfringens (CP) in populations of two benthic crabs (Neohelice granulata and Cyrtograpsus angulatus) and in sediment from the EBB. CP was found in 49.1% of the crabs and all of the isolates were identified as type A. The alpha (cpa) and enterotoxin (cpe) encoding genes were identified. Genetic analyses identified 13 novel sequence types, and found no clustering among isolates, suggesting that CP is not part of the crabs' commensal flora. CP carriage was 51 times more likely in crabs from the area nearest sewage outfalls compared with crabs from a reference site. Our in vitro experiments suggest that the carriage of CP in crabs is transient. The use of these benthic crabs as monitoring organisms of sewage pollution in coastal habitats is proposed.
Assuntos
Braquiúros/microbiologia , Clostridium perfringens , Esgotos/microbiologia , Animais , Argentina , Toxinas Bacterianas/genética , Proteínas de Ligação ao Cálcio/genética , Clostridium perfringens/genética , Clostridium perfringens/isolamento & purificação , Ecossistema , Estuários , Sedimentos Geológicos/microbiologia , Filogenia , Fosfolipases Tipo C/genética , Poluição da ÁguaRESUMO
Antibiotics have been included in the formulation of feed for livestock production for more than 40 years as a strategy to improve feed conversion rates and to reduce costs. The use of antimicrobials as growth-promoting factors (AGP) in sub-therapeutic doses for long periods is particularly favorable for the selection of antimicrobial resistant microorganisms. In the last years, global concern about development of antimicrobial resistance and transference of resistance genes from animal to human strains has been rising. Removal of AGP from animal diets involves tremendous pressure on the livestock and poultry farmers, one of the main consequences being a substantial increase in the incidence of infectious diseases with the associated increase in the use of antibiotics for therapy, and concomitantly, economic cost. Therefore, alternatives to AGP are urgently needed. The challenge is to implement new alternatives without affecting the production performances of livestock and avoiding the increase of antimicrobial resistant microorganisms. Plant extracts and purified derived substances are showing promising results for animal nutrition, either from their efficacy as well as from an economical point of view. Tannins are plant derived compounds that are being successfully used as additives in poultry feed to control diseases and to improve animal performance. Successful use of any of these extracts as feed additives must ensure a product of consistent quality in enough quantity to fulfill the actual requirements of the poultry industry. Chestnut (hydrolysable) and Quebracho (condensed) tannins are probably the most readily available commercial products that are covering those needs. The present report intends to analyze the available data supporting their use.
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Clostridium perfringens alpha and epsilon toxins produce enterotoxaemia in sheep and goats. However, the information regarding the pathophysiology of alpha and epsilon toxins in the bovine intestine is still scanty. In this study, intestinal loops were performed in the ileum and colon of three one-week-old Holstein and two four-week-old crossbreed calves. Laparotomy was performed in all calves under anaesthesia and four loops -three cm long- were performed in the small and large intestines. For both intestines, loops were inoculated with alpha or epsilon toxins. Tissue samples from all loops were obtained and processed for routine histology and for transmission electron microscopy. Congestion was observed in toxin treated loops. Fluid accumulation in the gut lumen was prominent in all treated loops, but in epsilon treated ones the mucous was also haemorrhagic. The histology revealed large amount of exfoliated epithelial cells in the lumen of alpha toxin treated loops and severe haemorrhage was observed in the lamina propria of epsilon toxin treated colonic loops. Despite some necrotic exfoliated enterocytes, no ultraestructural changes were observed in alpha toxin treated loops, though with epsilon toxin the loops exhibited dilation of the intercellular space in the mucosa of both, small and large intestines. These observations indicate that both, alpha and epsilon toxins can alter the intestinal barrier, in calves and are pathogenic for this species.
Assuntos
Toxinas Bacterianas/toxicidade , Proteínas de Ligação ao Cálcio/toxicidade , Clostridium perfringens/química , Intestinos/efeitos dos fármacos , Fosfolipases Tipo C/toxicidade , Animais , Toxinas Bacterianas/administração & dosagem , Proteínas de Ligação ao Cálcio/administração & dosagem , Bovinos , Enterócitos/patologia , Enterócitos/ultraestrutura , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Intestinos/patologia , Fosfolipases Tipo C/administração & dosagemRESUMO
Non-enterotoxin (CPE)-producing Clostridium perfringens type A has been associated with enteritis in calves. Recent evidence has suggested that a novel toxin, named beta2 (CPB2), is implicated in the pathogenesis of this disease, although there is little evidence supporting this. In the current study, the role of C. perfringens type A in an outbreak of enteritis in calves was studied. Two 20-day-old dairy calves exhibiting apathy and reluctance to eat, with paresis of the anterior limbs, were euthanized for postmortem examination. Gross and histological changes compatible with acute enteritis, rumenitis, meningitis, and pneumonia were seen in both calves. Clostridium perfringens type A non-CPE, non-CPB2 was isolated from the abomasum and the small intestine. Escherichia coli ONTH8 (with cdtBIII and f17 virulence genes detected by polymerase chain reaction) was also isolated from the brain, abomasum, and intestine from both calves. All the samples were negative for Salmonella spp. When the C. perfringens strain was inoculated into bovine ligated small and large intestinal loops, cell detachment, erosion, and hemorrhage of the lamina propria were observed, predominantly in the small intestine. The results suggest that non-CPE, non-CPB2 C. perfringens type A is able to induce pathologic changes in the intestine of calves, probably enhanced by other pathogens, such as some pathogenic E. coli strains.
Assuntos
Doenças dos Bovinos/microbiologia , Infecções por Clostridium/veterinária , Clostridium perfringens/isolamento & purificação , Enterite/microbiologia , Enterite/veterinária , Animais , Bovinos , Doenças dos Bovinos/diagnóstico , Doenças dos Bovinos/patologia , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/microbiologia , Infecções por Clostridium/patologia , Clostridium perfringens/genética , Enterite/diagnóstico , Enterite/patologia , Evolução Fatal , Feminino , Laparotomia/veterináriaRESUMO
Clostridium perfringens epsilon toxin (ETX) is responsible for a fatal enterotoxemia in different animal species, producing extensive renal damage, neurological disturbance and edema of lungs, heart and kidneys. However, there is no information about the susceptibility of humans to ETX. Here, we report that primary cultures of human renal tubular epithelial cells (HRTEC) exposed to ETX showed a marked swelling with subsequent large blebs surrounding most cells. The incubation of HRTEC with ETX produced a reduction of cell viability in a dose- and time-dependent manner. The CD(50) after 1-hour and 24-hour incubation were 3 µg/mL and 0.5 µg/mL, respectively. The pulse with ETX for 3 min was enough to produce a significant cytotoxic effect on HRTEC after 1-hour incubation. ETX binds to HRTEC forming a large complex of about 160 kDa similar to what was found in the Madin-Darby canine kidney (MDCK) cell line. The HRTEC could be a useful cell model to improve the understanding of the mechanisms involved on the cell damage mediated by ETX.
Assuntos
Toxinas Bacterianas/toxicidade , Células Epiteliais/efeitos dos fármacos , Túbulos Renais/efeitos dos fármacos , Toxinas Bacterianas/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Humanos , Túbulos Renais/metabolismo , Túbulos Renais/patologia , Ligação Proteica , Fatores de TempoRESUMO
Vegetable tannins are water-soluble polyphenolic compounds of varying molecular weights that occur abundantly in nature. The diet of many free-ranging wild animals contains significant amounts of tannins. Also, commercial tannins are used in animal industry as food additives to improve animal performance. In order to further determine the capacity of tannins to inhibit the development of intestinal diseases produced by Clostridium pefringens, we evaluated here the effect of tannins from quebracho, chestnut or combinations of both on C. perfringens and their toxins. The C. perfringens (types A, B, C, D and E) growth obtained from the intestine of healthy and diseased animals was reduced in a dose-dependent manner in the presence of quebracho tannins, chestnut tannins, combinations of both or a commercial formula based in these tannins. Although the minimal inhibitory concentration of both tannins varied between isolates, no statistically significant differences were observed between isolates from healthy or sick animals. Comparative analysis showed that the concentrations of quebracho tannin inhibiting the growth of C. perfringens were higher than chestnut tannin. In fact, antibacterial effect of quebracho tannin was increased up to 20 times with the addition of 25% of chestnut tannin and 85 times with 75% of chestnut tannin. Antibacterial activity of the commercial product was up to ~50 times higher than quebracho tannin alone. Quebracho tannin showed partial bactericidal activity, whereas chestnut tannin activity was stronger. Both tannins were able to reduce the alpha toxin lecithinase activity and epsilon toxin cytotoxicity in MDCK cells. These results suggest that tannin-supplemented diet could be useful to prevent some clostridial diseases.
Assuntos
Toxinas Bacterianas/metabolismo , Infecções por Clostridium/veterinária , Clostridium perfringens/efeitos dos fármacos , Enteropatias/veterinária , Taninos/farmacologia , Animais , Linhagem Celular , Infecções por Clostridium/microbiologia , Infecções por Clostridium/prevenção & controle , Clostridium perfringens/crescimento & desenvolvimento , Cães , Concentração Inibidora 50 , Enteropatias/microbiologia , Enteropatias/prevenção & controle , Testes de Sensibilidade Microbiana/veterinária , Estatísticas não ParamétricasRESUMO
Neurological damage caused by intoxication with Shiga toxin (Stx) from enterohemorrhagic Escherichia coli is the most unrepairable and untreatable outcome of Hemolytic Uremic Syndrome, and occurs in 30% of affected infants. In this work intracerebroventricular administration of Stx2 in rat brains significantly increased the expression of its receptor globotriaosylceramide (Gb(3)) in neuronal populations from striatum, hippocampus and cortex. Stx2 was immunodetected in neurons that expressed Gb(3) after intracerebroventricular administration of the toxin. Confocal immunofluorescence of microtubule-associated protein 2 showed aberrant dendrites in neurons expressing increased Gb(3). The pro-apoptotic Bax protein was concomitantly immunodetected in neurons and other cell populations from the same described areas including the hypothalamus. Confocal immunofluorescence showed that Gb(3) colocalized also with glial fibrillary acidic protein only in reactive astrocytic processes, and not in vehicle-treated normal ones. Rats showed weight variation and motor deficits as compared to controls. We thus suggest that Stx2 induces the expression of Gb(3) in neurons and triggers neuronal dysfunctions.
Assuntos
Encéfalo/efeitos dos fármacos , Dendritos/efeitos dos fármacos , Síndromes Neurotóxicas/microbiologia , Toxina Shiga II/toxicidade , Triexosilceramidas/agonistas , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Biomarcadores/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Chlorocebus aethiops , Dendritos/metabolismo , Dendritos/patologia , Infecções por Escherichia coli/complicações , Proteína Glial Fibrilar Ácida/metabolismo , Imuno-Histoquímica , Injeções Intraventriculares , Masculino , Microscopia Confocal , Proteínas Associadas aos Microtúbulos/metabolismo , Degeneração Neural/metabolismo , Degeneração Neural/microbiologia , Degeneração Neural/patologia , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/patologia , Ratos , Ratos Sprague-Dawley , Triexosilceramidas/metabolismo , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologia , Células Vero , Proteína X Associada a bcl-2/efeitos dos fármacos , Proteína X Associada a bcl-2/metabolismoRESUMO
Epsilon toxin is a potent neurotoxin produced by Clostridium perfringens types B and D, an anaerobic bacterium that causes enterotoxaemia in ruminants. In the affected animal, it causes oedema of the lungs and brain by damaging the endothelial cells, inducing physiological and morphological changes. Although it is believed to compromise the intestinal barrier, thus entering the gut vasculature, little is known about the mechanism underlying this process. This study characterizes the effects of epsilon toxin on fluid transport and bioelectrical parameters in the small intestine of mice and rats. The enteropooling and the intestinal loop tests, together with the single-pass perfusion assay and in vitro and ex vivo analysis in Ussing's chamber, were all used in combination with histological and ultrastructural analysis of mice and rat small intestine, challenged with or without C. perfringens epsilon toxin. Luminal epsilon toxin induced a time and concentration dependent intestinal fluid accumulation and fall of the transepithelial resistance. Although no evident histological changes were observed, opening of the mucosa tight junction in combination with apoptotic changes in the lamina propria were seen with transmission electron microscopy. These results indicate that C. perfringens epsilon toxin alters the intestinal permeability, predominantly by opening the mucosa tight junction, increasing its permeability to macromolecules, and inducing further degenerative changes in the lamina propria of the bowel.
Assuntos
Toxinas Bacterianas/metabolismo , Enterotoxemia/microbiologia , Intestino Delgado/efeitos dos fármacos , Permeabilidade/efeitos dos fármacos , Animais , Eletrofisiologia , Enterócitos/metabolismo , Feminino , Mucosa Intestinal/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica de Transmissão/métodos , Ratos , Ratos WistarRESUMO
Clostridium perfringens type D-producing epsilon toxin is a common cause of death in sheep and goats worldwide. Although anti-epsilon toxin serum antibodies have been detected in healthy non-vaccinated sheep, the information regarding naturally acquired antibodies in ruminants is scanty. The objective of the present report was to characterize the development of naturally acquired antibodies against C. perfringens epsilon toxin in goats. The levels of anti-epsilon toxin antibodies in blood serum of goat kids from two different herds were examined continuously for 14 months. Goats were not vaccinated against any clostridial disease and received heterologous colostrums from cows that were not vaccinated against any clostridial disease. During the survey one of these flocks suffered an unexpectedly severe C. perfringens type D enterotoxemia outbreak. The results showed that natural acquired antibodies against C. perfringens epsilon toxin can appear as early as 6 weeks in young goats and increase with the age without evidence of clinical disease. The enterotoxemia outbreak was coincident with a significant increase in the level of anti-epsilon toxin antibodies.
Assuntos
Anticorpos Antibacterianos/biossíntese , Toxinas Bacterianas/imunologia , Clostridium perfringens/imunologia , Surtos de Doenças/veterinária , Enterotoxemia/imunologia , Doenças das Cabras/microbiologia , Animais , Animais Recém-Nascidos , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Brasil/epidemiologia , Estudos de Coortes , Enterotoxemia/epidemiologia , Enterotoxemia/microbiologia , Ensaio de Imunoadsorção Enzimática/veterinária , Feminino , Doenças das Cabras/epidemiologia , Doenças das Cabras/imunologia , Cabras , Cinética , Estudos Longitudinais , MasculinoRESUMO
The immunomodulating properties of a low cholera toxin (CT) dose over the systemic antibody response against Vibrio cholerae antigens after a comparatively extensive period of time were evaluated. Groups of 10 mice were injected intraperitoneally three times at 0, 30 and 86 days with 500 microl of buffer or 10(8) viable recombinant V. cholerae bacteria (lacking cholera toxin A subunit) with or without 100 ng of CT. Sera were obtained from inoculated mice at 0, 14, 28, 37, 58, 80, 93, 114, 236 and 356 days after the first injection. Vibriocidal activity and IgM and IgG anti-lipopolysaccharide (LPS) or outer membrane protein (OMP) antibodies levels were estimated by ELISA in sera of inoculated mice. Anti-LPS IgG subclasses were measured 2 weeks after each immunization by ELISA. Treatment of mice with CT markedly influenced the immune response to LPS but not against OMP of V. cholerae. Simultaneous intraperitoneal administration of CT with V. cholerae resulted in marked enhancement of both IgM anti-LPS and vibriocidal titers which subsisted for a relatively extensive period of time after repeated antigen administration. No differences were observed in IgM and IgG anti-OMP titers after extended periods of time between CT and control treatments. A similar pattern of IgG anti-LPS subclasses was observed in the serum samples analyzed. These results suggest that long term CT administration modulates the IgM anti-V. cholerae LPS response and the serum vibriocidal activity.
Assuntos
Anticorpos Antibacterianos/sangue , Proteínas da Membrana Bacteriana Externa/imunologia , Toxina da Cólera/administração & dosagem , Toxina da Cólera/imunologia , Cólera/imunologia , Lipopolissacarídeos/imunologia , Administração Oral , Animais , Anticorpos Antibacterianos/imunologia , Ensaio de Imunoadsorção Enzimática , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Injeções Intraperitoneais , Injeções Subcutâneas , Camundongos , Vibrio cholerae/imunologiaRESUMO
Enterotoxemia caused by Clostridium perfringens type D is a highly lethal disease of sheep, goats and other ruminants. The diagnosis of this condition is usually confirmed by detection of epsilon toxin, a major exotoxin produced by C. perfringens types B and D, in the intestinal content of affected animals. It has been suggested that other body fluids can also be used for detection of epsilon toxin. This study was performed to evaluate the usefulness of intestinal content versus other body fluids in detecting epsilon toxin in cases of sheep enterotoxemia. Samples of duodenal, ileal and colon contents, pericardial and abdominal fluids, aqueous humor and urine from 15 sheep with experimentally induced enterotoxemia, were analysed for epsilon toxin using a capture ELISA. Epsilon toxin was detected in 92% of the samples of ileal content, 64% of the samples of duodenal content, 57% of the samples of colon content and in 7% of the samples of pericardial fluid and aqueous humor. No epsilon toxin was found in samples of abdominal fluid or urine from the animals with enterotoxemia or in any samples from six clinically healthy sheep used as negative controls. The results of this study indicate that with the diagnostic capture ELISA used, intestinal content (preferably ileum) should be used for C. perfringens type D epsilon toxin detection in suspected cases of sheep enterotoxemia.
Assuntos
Toxinas Bacterianas/análise , Líquidos Corporais/química , Clostridium perfringens/química , Enterotoxemia/diagnóstico , Doenças dos Ovinos/diagnóstico , Animais , Clostridium perfringens/patogenicidade , Enterotoxemia/microbiologia , Intestinos/química , Doenças dos Ovinos/microbiologia , Carneiro Doméstico , Urina/químicaRESUMO
OBJECTIVE: To evaluate the morphologic and physiologic changes induced by Clostridium perfringens type A (alpha toxin in the ileum and colon of sheep. SAMPLE POPULATION: 16 ligated intestinal loops in 4 Merino lambs and 18 explants of ileum and colon from slaughtered lambs. PROCEDURE: alpha Toxin-induced fluid accumulation was evaluated in ligated ileal and colonic loops of sheep. Tissues were evaluated morphologically by use of gross and histologic examination. Effects of toxin on in vitro intestinal net water transport were tested in modified Ussing chambers. RESULTS: Ovine ileal and colonic loops incubated with C perfringens type A alpha toxin retained more fluid than control loops. Histologically, in the ileum of lambs inoculated with 300 LD50 of alpha toxin/mL, there was a mild to moderate multifocal infiltration of neutrophils in the lamina propria and submucosa. The colonic loops of lambs inoculated with 30 or 300 LD50 of alpha toxin/mL had excessive mucus in the lumen, a moderate amount of neutrophils mixed with mucus in the intestinal lumen, and moderate multifocal infiltration of the lamina propria and submucosa with neutrophils; the blood vessels of these layers were engorged with neutrophils. In vitro measurements of water transport also revealed inhibition of net epithelial water absorption in ileum and colon incubated with alpha toxin on the mucosal side. CONCLUSIONS AND CLINICAL RELEVANCE: These results indicate that alpha toxin induces alterations in sheep intestine. Clostridium perfringens type A organisms that produce alpha toxin could be responsible for diseases of intestinal origin in some ruminants.