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Strains of enterotoxigenic Escherichia coli (ETEC) causing post-weaning diarrhoea (PWD) in piglets have a widespread and detrimental impact on animal health and the economics of pork production. Traditional approaches to control and prevention have placed a strong emphasis on antimicrobial use (AMU) to the extent that current prevalent porcine ETEC strains have developed moderate to severe resistance. This complicates treatment of ETEC infection by limiting therapeutic options, increasing diagnostic costs and increasing mortality rates. Management factors, the use of supra-physiological levels of zinc oxide and selected feed additives have all been documented to lower the incidence of ETEC infection in pigs; however, each intervention has its own limitations and cannot solely be relied upon as an alternative to AMU. Consequently, treatment options for porcine ETEC are moving towards the use of newer antimicrobials of higher public health significance. This review focuses on microorganisms and microbial-derived products that could provide a naturally evolved solution to ETEC infection and disease. This category holds a plethora of yet to be explored possibilities, however studies based around bacteriophage therapy, probiotics and the use of probiotic fermentation products as postbiotics have demonstrated promise. Ultimately, pig producers and veterinarians need these solutions to reduce the reliance on critically important antimicrobials (CIAs), to improve economic and animal welfare outcomes, and to lessen the One Health threat potentiated by the dissemination of AMR through the food chain., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Dietary tryptophan (Trp) is a precursor for serotonin, a neuromediator involved in stress responses. Tryptophan competes with other large neutral amino acids (LNAA: tyrosine, isoleucine, leucine, valine, and phenylalanine) to cross the blood-brain barrier; therefore, the regulation of circulating LNAA can influence Trp availability in the cortex and serotonin biosynthesis. The hypothesis examined in this study was that increased supplementation of dietary Trp and a reduction in LNAA for weaned pigs experimentally infected with enterotoxigenic Escherichia coli (ETEC; F4) will increase Trp availability in plasma and reduce indices of the stress response, which will translate to reduced production losses. At 21 ± 3 d of age (mean ± SEM), 96 male pigs (Large White × Landrace) weighing 6.3 ± 0.98 kg (mean ± SEM) were individually penned and allocated to a 4 × 2 factorial arrangement of treatments, with respective factors being 1) four dietary standardized ileal digestible (SID) Trp and LNAA contents, being HTrpHLNAA (Low Trp-High LNAA; 0.24% SID Trp: 5.4% SID LNAA), HTrpHLNAA (Low Trp-Low LNAA; 0.24% SID Trp: 4.6% SID LNAA), HTrpHLNAA (High Trp-High LNAA; 0.34% SID Trp: 5.4% SID LNAA), and HTrpHLNAA (High Trp-Low LNAA; 0.34% SID Trp: 4.6% SID LNAA), and 2) without/with ETEC infection. Pigs were orally infected with 0.8 mL (3.6 × 109 CFU/mL) ETEC at days 7 and 8 after weaning. Pigs fed diets high in Trp irrespective of the level of LNAA (HTrpHLNAA and HTrpLLNAA) had higher plasma Trp concentrations (P < 0.001) and a Trp:LNAA ratio (P < 0.001) before infection and 6 d after infection. Following infection, noninfected pigs had higher plasma Trp (P = 0.03) and a Trp:LNAA ratio (P = 0.004) compared with pigs infected with ETEC. Plasma cortisol levels after infection were higher in ETEC-infected pigs (P = 0.05) and altering dietary Trp and LNAA concentrations did not influence (P > 0.05) plasma cortisol. Pigs fed diet HTrpLLNAA had higher serum serotonin levels 24 h after infection (P = 0.02) compared with pigs fed diets LTrpLLNAA and HTrpHLNAA. Similarly, pigs fed diet HTrpLLNAA had a higher (P = 0.02) average daily gain during the 3-wk study. Overall, average daily feed intake tended to be higher in pigs fed an HTrpLLNAA diet compared with the other diets (P = 0.08). These results suggest that the increased supplementation of dietary Trp with reduced LNAA increased circulating Trp levels that, in turn, likely caused higher serum serotonin levels, irrespective of infection with ETEC, and improved aspects of post-weaning performance., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

An infection model with enterotoxigenic Escherichia coli (ETEC) harboring the F4 fimbriae can be used to assess the impacts that various challenges associated with weaning (e.g., dietary, psychological, environmental) have on the expression of postweaning diarrhea. The objective of this study was to develop a novel inoculation method for administering an ETEC culture that would induce a higher proportion of ETEC-F4 diarrhea, in pigs that genetically showed ETEC-F4 susceptibility or resistance. The study was designed as a factorial arrangement of treatments with the factors being 1) partially susceptible or resistant to ETEC-F4 based on genetic testing, and 2) 4 challenge treatments, being a) a conventional liquid broth method using a drenching gun [Positive control (PC)], b) a Syringe method, c) a Capsule method, and d) Negative control [pigs not challenged (NC)]. At 21 ± 3 d of age (mean ± SEM), 48 male castrate pigs (Large White × Landrace) weighing approximately 7.0 ± 1.18 kg were allocated to 4 treatment groups in 2 replicate pens (6 pigs per pen). Initial ETEC-F4 susceptibility was based on a DNA marker test and each treatment group had 9 partially susceptible and 3 resistant pigs. On days 7 and 8 after weaning, pigs were challenged with ETEC (serotype O149:K88; toxins LT1, ST1, ST2, and EAST). On each inoculation day the PC pigs were orally dosed with 9 mL 7.12 × 109 colony-forming unit (CFU), the Syringe pigs with 0.8 mL 6.72 × 109 CFU, the Capsule pigs were orally administered 2 capsules containing 0.8 mL 3.28 × 109 CFU, and the NC pigs 1 mL of phosphate-buffered saline (PBS) solution. Approximately 72 h after infection, 44, 22, 78, and 0% of partially susceptible pigs in the PC, the Syringe, the Capsule, and the NC group had developed ETEC-F4 diarrhea (P = 0.007). Partially susceptible pigs had a higher diarrhea index (DI) compared to resistant pigs (31.5 vs. 4.8, P < 0.001). The NC group had a lower DI compared to the PC and Capsule pigs (3.9, 38.1, and 40.3, respectively, P < 0.005). Following infection, genetically resistant pigs in the Capsule group had a DI of zero and the partially susceptible pigs had a DI of 55.6 (P = 0.014). This study showed that genetically screening pigs and using a Capsule to deliver ETEC-F4 can increase cases of diarrhea and the efficiency of the challenge model. Taken together, these methods have the potential to reduce the number of pigs needed in future experimental infection studies., (© The Author(s) 2019. Published by Oxford University Press on behalf of the American Society of Animal Science.)

This experiment examined if immune system stimulation of weaner pigs, initiated by inoculation an enterotoxigenic strain of Escherichia coli (ETEC), increased the requirement for dietary tryptophan (Trp), modulated the inflammatory response, altered plasma levels of Trp and its metabolite kynurenine (Kyn) and effected post-weaning diarrhoea. Individually housed pigs (n = 72) weaned at 21 d of age were allocated to one of six treatments (n = 12) according to a two by three factorial arrangement of (1) with or without ETEC infection and (2) three dietary ratios of standardised ileal digestible (SID) Trp to lysine (Lys) (SID Trp:Lys) of 0.16, 0.20 or 0.24, in a completely randomised block design. Pigs had ad libitum access to diets (per kg 14.13 MJ ME, 12.4 g SID Lys, 195 g crude protein) for 3 weeks after weaning. Pigs were infected with ETEC (O149:K98:K88) at 72, 96 and 120 h after weaning and then bled on day 3, 11 and 19. An increased dietary Trp:Lys ratio increased plasma Trp and Kyn (p < 0.001) without effect of infection. On day 3, pigs fed 0.24 SID Trp:Lys had lower levels of plasma urea than at 0.20 Trp:Lys (p = 0.047) and on day 11, plasma urea was lower at 0.20 than at 0.16 SID Trp:Lys (p = 0.007). Infection increased (p = 0.039) the diarrhoea index and deteriorated faecal consistency from day 4-10 (p < 0.05). Treatments did not affect haptoglobin and acid soluble glycoprotein levels or daily gain and feed intake. However, 0.24 SID Trp:Lys improved (p = 0.021) feed efficiency without an effect of infection. In conclusion, in the absence of dietary antibiotic growth promotants, increasing the dietary SID Trp:Lys ratio to 0.24 improved feed conversion ratio after weaning and increased plasma levels of Trp and Kyn regardless of infection with E. coli.

For the last several decades, antimicrobial compounds have been used to promote piglet growth at weaning through the prevention of subclinical and clinical disease. There are, however, increasing concerns in relation to the development of antibiotic-resistant bacterial strains and the potential of these and associated resistance genes to impact on human health. As a consequence, European Union (EU) banned the use of antibiotics as growth promoters in swine and livestock production on 1 January 2006. Furthermore, minerals such as zinc (Zn) and copper (Cu) are not feasible alternatives/replacements to antibiotics because their excretion is a possible threat to the environment. Consequently, there is a need to develop feeding programs to serve as a means for controlling problems associated with the weaning transition without using antimicrobial compounds. This review, therefore, is focused on some of nutritional strategies that are known to improve structure and function of gastrointestinal tract and (or) promote post-weaning growth with special emphasis on probiotics, prebiotics, organic acids, trace minerals and dietary protein source and level., (© 2012 Blackwell Verlag GmbH.)

A total of sixty surgically castrated male pigs (Large White × Landrace) weighing 31·2 (sd 4·3) kg were used in a randomised block experiment to examine the effect of added dietary inulin (0, 20, 40 and 80 g/kg) on the occurrence of swine dysentery (SD) and on fermentation characteristics in the large intestine after experimental challenge with the causative spirochaete Brachyspira hyodysenteriae. The pigs were allowed to adapt to the diets for 2 weeks before each pig was challenged orally four times with a broth culture containing B. hyodysenteriae on consecutive days. Increasing dietary levels of inulin linearly (P = 0·001) reduced the risk of pigs developing SD; however, eight out of fifteen pigs fed the diet with 80 g/kg inulin still developed the disease. The pH values in the caecum (P = 0·072) tended to decrease, and in the upper colon, the pH values did decrease (P = 0·047) linearly with increasing inulin levels in the diets, most probably due to a linear increase in the concentration of total volatile fatty acids in the caecum (P = 0·018), upper colon (P = 0·001) and lower colon (P = 0·013). In addition, there was a linear reduction in the proportion of the branched-chain fatty acids isobutyric acid and isovaleric acid in the caecum (P = 0·015 and 0·026) and upper colon (P = 0·011 and 0·013) with increasing levels of dietary inulin. In conclusion, the present study showed that a diet supplemented with a high level of inulin (80 g/kg) but not lower levels reduced the risk of pigs developing SD, possibly acting through a modification of the microbial fermentation patterns in the large intestine.

Swine dysentery is a contagious mucohemorrhagic diarrheal disease caused by the intestinal spirochete Brachyspira hyodysenteriae that colonizes and induces inflammation of the cecum and colon. It has been reported that a diet containing chicory root and sweet lupin can prevent swine dysentery. This experiment was conducted to test the hypothesis that inulin in the chicory root rather than galactans in lupins was responsible for protective effects. An experiment with a 2 × 2 factorial arrangement of treatments was undertaken using pigs fed barley- and triticale-based diets, with the main effects being protein source [185 g/kg of canola meal (decreased galactans) or 220 g/kg of lupins (greater galactans)] and inulin supplementation (0 or 80 g/kg). Forty Large White × Landrace pigs weighing 21 ± 3 kg, with 10 pigs per diet, were allowed to adapt to the diets for 2 wk, and then each pig was challenged orally 4 times with a broth culture containing B. hyodysenteriae on consecutive days. Pigs were killed when they showed clinical signs of dysentery or 6 wk postchallenge. Pigs fed diets without inulin had 8.3 times greater risk (P = 0.017) of developing swine dysentery and were 16 times more likely (P = 0.004) to have colon contents that were culture-positive for B. hyodysenteriae, compared with the pigs fed a diet with 80 g/kg of inulin. Diets containing lupins did not prevent pigs from developing clinical swine dysentery; however, inclusion of lupins or inulin or both in the diets delayed the onset of disease compared with the diet based mainly on canola meal (P < 0.05). Diet did not influence the total concentration of organic acids in the ileum, cecum, or upper and lower colon; however, the molar proportions of the organic acids were influenced (P < 0.05). Consequently the pH values in the cecum, and upper and lower colon were not influenced (P > 0.05) by diet. However the pH values of the ileal digesta were decreased in pigs fed the diet with both lupins and inulin compared with the diet containing only lupins (P < 0.05). In conclusion, this study shows that diets supplemented with highly fermentable carbohydrates from inulin protected pigs against developing swine dysentery.

This study evaluated the effect of feeding low protein (LP) diets for 7 or 14 d after weaning or a high protein (HP) diet for 14 d after weaning on postweaning diarrhea (PWD), indices of protein fermentation, and production in pigs infected or not infected per os with an enterotoxigenic strain of Escherichia coli. A total of 72 female pigs weaned at aged 21 d with initial BW of 5.9 +/- 0.12 kg were used in a 3 x 2 factorial arrangement of treatments. The factors were 3 feeding regimens associated with different combinations of feeding duration and diet CP level: (i) HP diet (256 g of CP/kg) fed for 14 d after weaning, (ii) LP diet (175 g of CP/kg) fed for 7 d after weaning, and (iii) LP diet fed for 14 d after weaning; and infection or noninfection with an enterotoxigenic strain of E. coli (10(7) cfu/mL, serotype O149:K91:K88) at 72, 96, and 120 h after weaning. The LP diets were fortified with crystalline Ile and Val to achieve an ideal AA pattern. A second-stage diet (213 g of CP/kg) was fed to pigs at the conclusion of each feeding regimen, and the study finished 4 wk after weaning. None of the diets contained antimicrobials. Feeding the LP diets decreased (P < 0.001) plasma urea nitrogen, fecal ammonia nitrogen concentrations, and the incidence of PWD, but increased (P = 0.001) fecal DM content compared with pigs fed HP in the 2-wk period after weaning. Infection increased shedding of beta-hemolytic E. coli (P < 0.001), the incidence of PWD (P < 0.001), and fecal ammonia nitrogen concentrations (P < 0.01), but did not interact with feeding regimen, after weaning. Pigs challenged with E. coli grew more slowly (P < 0.001) and had decreased G:F (P < 0.01) compared with nonchallenged pigs in the 4-wk period after weaning. Feeding an LP diet for 7 or 14 d after weaning markedly reduced the incidence of PWD after infection with beta-hemolytic E. coli. Infection was associated with decreased indices of protein fermentation in the distal gastrointestinal tract but did not compromise the growth of weaner pigs in the 4-wk period after weaning.

The purpose of this study was to evaluate the effects of feeding pigs with inulin and/or benzoic acid on post-weaning diarrhoea (PWD), indices of fermentation in the gastrointestinal tract, and production in pigs experimentally infected with an enterotoxigenic strain of Escherichia coli (ETEC). Forty-eight entire male pigs (Large White×Landrace) aged 21 ± 3 days of age and weighing 4.97 ± 0.08 kg (mean ± SE) were used in a 2×2 factorial experiment, with the respective factors being inulin (0 versus 8%) and benzoic acid (0 vs. 0.5%). Feeding inulin-supplemented diets improved (p = 0.022) the faecal consistency (FC) and reduced (p = 0.001) the incidence of PWD; however, the use of benzoic acid had no effects on PWD or faecal ETEC shedding. Wet faeces (a higher FC score) were associated with increased faecal ETEC shedding (R(2) = 0.394, p = 0.001). Inulin reduced the total concentrations of short chain fatty acids (p = 0.029) in the proximal colon. The total concentration of lactic acid was increased by inulin in the caecum (p = 0.007) and proximal colon (p = 0.002). Feeding inulin or benzoic acid had no effects on production after weaning.

An experiment was conducted to determine whether adding oat hulls to weaner pig diets based on extruded rice or unprocessed wheat influenced post-weaning diarrhoea (PWD) and protein fermentation in the large intestine. Ninety-six male piglets (5.16 (SEM 0.08) kg) were allocated to (i) extruded rice plus animal proteins (RAP); (ii) RAP with added oat hulls (20 g/kg); (iii) wheat plus animal proteins (WAP); (iv) WAP with added oat hulls (20 g/kg). Blood and faecal samples were collected on days 7 and 14 after weaning at about age 21 d. Pigs fed RAP had more PWD than pigs fed WAP (P < 0.05). Oat hull supplementation to diet RAP decreased the incidence of PWD (P < 0.05). The total-tract digestibility of DM, starch and energy was higher in rice-based diets than in wheat-based diets (P < 0.001); however, oat hulls decreased digestibility of DM and gross energy (P < 0.001). Pigs fed RAP had higher plasma creatinine concentrations (P < 0.01), which were positively correlated to cumulative beta-haemolytic Escherichia coli scores after weaning (R2 0.928; P = 0.015). Addition of oat hulls decreased plasma urea concentrations only in pigs fed RAP (interaction; P < 0.05). Pigs fed RAP had lower faecal total biogenic amine concentrations than pigs fed WAP (P < 0.001). Oat hull supplementation tended to decrease total biogenic amine concentrations (P = 0.103). These data indirectly suggest that a mostly insoluble dietary fibre source such as oat hulls can decrease PWD in dietary situations where there may be a misbalance of carbohydrate to protein entering the hindgut.

The weaning of piglets is often associated with digestive disorders, particularly diarrhea--postweaning colibacillosis (PWC)--which is caused by infection with enterotoxigenic strains of Escherichia coli. It has been shown previously that a diet for newly weaned pigs based on cooked white rice and animal protein decreases the occurrence of PWC, whereas the addition of carboxymethylcellulose (CMC) to this diet enhances PWC. The aims of the current work were to 1) determine whether substitution of animal protein with plant proteins in the cooked-white-rice diet influenced its protective effects on PWC and 2) confirm that an increase in viscosity of the digesta by adding CMC to the diet favors the development of PWC--with (Exp. 1) or without (Exp. 2) experimental infection of piglets with E. coli. The diets were 1) cooked white rice and animal protein sources (RAP), 2) RAP + CMC added at 40 g of CMC/kg (air-dry basis) of diet, 3) cooked white rice and plant protein sources (RPP), and 4) wheat and plant protein sources (WPP). Experiments 1 and 2 were conducted using 32 and 24 piglets (eight and six per treatment), respectively. Piglets were weaned at 21 d (d 1), and fed ad libitum until slaughter on d 9. In Exp. 1, piglets were orally infected with enterotoxigenic E. coli on d 4, 5, 6, and 7. On d 8 of Exp. 1, the E. coli scores in feces of pigs fed RAP + CMC were higher than with RAP (P < 0.01). On d 9 after weaning, feces from pigs fed diet RAP were normal or moist, whereas feces from pigs fed RAP + CMC were wet to diarrheic. On d 7 of Exp. 2, pigs fed diets RAP + CMC and WPP had wetter feces than pigs fed diets RAP or RPP (P < 0.05). On d 8, the E. coli scores in feces were higher (P < 0.01) with pigs fed RAP + CMC than with all other diets. The E. coli scores in the digesta were also higher with pigs fed RAP + CMC, and to a lesser extent with diet WPP, than with pigs fed RAP or RPP (P < 0.01). The large intestine was heavier in pigs fed diets RPP and WPP, and the digesta were more acidic (P < 0.05). This study confirmed that diet RAP was protective against PWC, and that substitution of animal proteins with plant protein in a rice-based diet did not diminish its protective effects. The addition of CMC to cooked white rice increased digesta viscosity and enhanced PWC. Consequently, this diet represents a useful model for studying this condition.

This study evaluated the effects of adding soluble fibre to the diet of healthy weaner pigs and weaner pigs experimentally infected with enterotoxigenic Escherichia coli (ETEC) in a model of post-weaning colibacillosis. Bodyweight gain, intestinal changes and proliferation of ETEC were measured 7 days following weaning. The basal diet consisted of pregelatinised rice fortified with animal protein. Addition of guar gum to this diet elevated the soluble fibre content from 1 to 6 per cent, and was associated with reduced bodyweight gains, increased large intestinal weights and fermentation, and increased proliferation of ETEC in the small intestine. The optimal levels and type of dietary fibre used for weaner pig diets require further evaluation., (Copyright 1999 Harcourt Publishers Limited.)

Swine dysentery (SD) is a disease which can be controlled by feeding a diet low in dietary fibre. The influence of source and inclusion level of dietary fibre both on bacterial populations in the colon, and on subsequent development of SD in pigs experimentally infected with Serpulina hyodysenteriae was evaluated. In Experiment 1, pigs were fed a low-fibre diet based on cooked rice and a animal protein supplement, or the same diet containing added insoluble (iNSP, fed as oaten chaff) or soluble (sNSP, fed as guar gum) non-starch polysaccharides, resistant starch (RS), or a combination of the last two (sNSP/RS). In Experiment 2, different levels of RS were added to the diet. With the base rice diet and with the addition of iNSP, the total number of colonic bacteria was low, the Gram-positive population predominated, S. hyodysenteriae did not colonize and SD did not develop. Synergistic bacteria (Fusobacterium necrophorum and Fus. nucleatum), which have been reported to facilitate colonization by S. hyodysenteriae, were found only among isolates from pigs fed the sNSP/RS diet, and these animals developed SD. Addition of RS to the diet increased total bacterial counts and stimulated growth of Gram-negative bacteria in the colon. In Experiment 1, this permitted colonization by S. hyodysenteriae, but not expression of SD. In contrast, in Experiment 2, this level of inclusion and two others allowed both colonization and development of SD. In conclusion, the addition of sNSP and/or RS to an otherwise protective rice-based diet generated changes in the large intestine microbiota which might have some influence on proliferation of S. hyodysenteriae and the development of SD.

Two experiments were conducted to test the hypothesis that feeding diets which limit the amount of fermentable substrate entering the large intestine would protect pigs against experimental infection with Serpulina hyodysenteriae, the causative agent of swine dysentery. Experiment 1 examined the effect of grain processing (hammer milling vs. steam flaking) and grain type (barley, groats, corn, sorghum and wheat) on indices of fermentation in the large intestine and the incidence of swine dysentery. Experiment 2 examined the role of five diets, steam-flaked corn, steam-flaked sorghum, hammer-milled wheat, extruded wheat and cooked white rice, on these same measures. All diets contained an animal protein supplement and no antibiotics. Pigs fed diets based on steam-flaked corn and steam-flaked sorghum had a lower incidence of disease (11-33%) than pigs fed diets based on other grains (75-100%). Pigs fed the diet based on cooked white rice were fully protected against swine dysentery. Both the soluble non-starch polysaccharide (NSP) concentration and the total NSP concentration of the diets explained a significant proportion of the variation in swine dysentery (R2 = 0.56, P = 0.016, and R2 = 0.71, P = 0.002, respectively), such that pigs eating diets containing <1.0 g/100 g soluble NSP showed reduced disease. However, pigs fed corn, sorghum and steam-flaked sorghum (Experiment 2), which contained only 0.4-0.5 g/100 g soluble NSP, still had a high incidence of disease (>50%). This was attributable to a higher level of resistant starch present in these grains. These data provide evidence that the expression of swine dysentery is associated with an increased concentration of fermentable substrate entering the large intestine.