The weaning and transport process has the potential to induce stress and cause intestinal dysfunction in pigs due to feed withdrawal, changes in social hierarchy that lead to fighting, moving into a new environment, handling, maternal separation, and increased disease pressure (de Groot et al., 2001; Toscano et al., 2007; Remience et al., 2008; Lallès and David, 2011; Merlot et al., 2011; Ott et al., 2014). As a result, post-weaning growth performance is often reduced (Randolph et al., 1981; Hyung et al., 1998), disease incidence is increased (Wirtz et al., 2007; Song et al., 2014), and morbidity and mortality can occur (Jayaraman and Nyachoti, 2017). Several mitigation strategies have been investigated and implemented to improve post-weaning and transport growth performance and overall pig health and intestinal function. These can include management strategies (e.g., environmental management, weaning age, etc.), dietary manipulations (e.g., corn particle size, palatability, etc.), feed additives (e.g., L-glutamine, fatty acids, etc.), and the provision of prophylactic dietary antibiotics (Smith et al., 2010; Duttlinger et al., 2019; Figueroa et al., 2019; Modina et al., 2019; Puls et al., 2019; McConn et al., 2020; Wensley et al., 2021). However, despite these strategies, weaning and transport continue to hinder pig growth. Therefore, an improved understanding of the mechanisms underlying weaning and transport-induced intestinal dysfunction is required to further improve upon and develop more effective mitigation strategies ^{1 , 2 , 3} .

Intestinal dysfunction in weaned and/or transported pigs is characterized by villus atrophy (Moeser et al., 2007a; Smith et al., 2010), reduced brush-border enzyme activity (Edelblum and Turner, 2009; Groschwitz and Hogan, 2009; Turner, 2009; Marchiando et al., 2010), and greater intestinal permeability (Barbara, 2006; Camilleri and Gorman, 2007; Edelblum and Turner, 2009; Marchiando et al., 2010). Although the mechanisms underlying weaning and transport-induced intestinal dysfunction are multifactorial and interrelated (Moeser et al., 2017), previous research indicates that stress induced corticotrophin releasing factor (CRF) signaling in the intestine may play a role (Moeser et al., 2007a; Smith et al., 2010). This dysfunction is thought to be mediated by CRF binding to CRF receptor 1 (CRFR1) and CRF receptor 2 (CRFR2) in the intestines (Taché et al., 2004), with CRFR1 activation resulting in more negative downstream effects on intestinal function (i.e., intestinal secretion, visceral hypersensitivity, and motility changes; Maillot et al., 2000; Taché et al., 2002; Million et al., 2003; Schwetz et al., 2005). During stressful events, CRF is released from the hypothalamus which activates CRF signaling in the intestines. As a result, mast cell counts and tumor necrosis factor alpha (TNFα) are increased, which may mediate increased intestinal permeability (Moeser et al., 2007a; Smith et al., 2010; Pohl et al., 2017). Although it is known that CRF plays a direct role in mediating intestinal dysfunction in newly weaned pigs under controlled conditions (Moeser et al., 2007a; Smith et al., 2010), it is currently unknown whether this response occurs under production relevant conditions or whether CRF signaling interacts with commonly used dietary mitigation strategies (e.g., prophylactic antibiotics).

The study objectives were 1) to evaluate the effects of CRF receptor signaling on measures of intestinal function in weaned and transported pigs, and 2) to evaluate the interaction between CRF receptor signaling and a prophylactic antibiotic combination commonly provided following weaning and transport in the United States [chlortetracycline (Aureomycin, Zoetis, Parsippany, NJ) + tiamulin (Denagard, Elanco Animal Health, Greenfield, IN); Puls et al., 2019] on measures of intestinal function in newly weaned and transported pigs. Based upon previous research (Moeser et al., 2007a; Smith et al., 2010), we hypothesized that CRF receptor signaling would mediate weaning and transport-induced intestinal dysfunction under production relevant conditions and that blocking CRF receptor signaling during the weaning and transport process would improve measures of intestinal function similarly to the administration of commonly provided prophylactic antibiotics following weaning and transport.

Young pigs encounter stressors such as weaning and transportation, which can result in intestinal barrier dysfunction (Spreeuwenberg et al., 2001; Boudry et al., 2004; Moeser et al., 2007a). In response to weaning and transportation stress, CRF, ACTH, and cortisol are released from the hypothalamus, anterior pituitary, and adrenal glands, respectively (Martinez et al., 1997; Taché et al., 1999; Meddings and Swain, 2000; Soderholm et al., 2002; Taché et al., 2004). As such, both cortisol and ACTH are often elevated in newly weaned and/or transported pigs (Perremans et al., 2001; Kanitz et al., 2002; Moeser et al., 2007a; Roldan-Santiago et al., 2013; Maskal et al., 2020). In agreement with these previous reports, circulating cortisol levels in the present study were greater 12 h Post-T when compared to Pre-T, regardless of the CRFA injection treatment. However, the CRFA pigs had a blunted cortisol response relative to SAL pigs. This blunted cortisol response likely indicates that the CRFA injection treatment was effective as previous research in monkeys have shown Astressin B prevents a stress-induced rise in cortisol (Berga, 2008). Although cortisol was reduced, no transport or CRFA-related ACTH differences were observed following weaning and transport in the present study. This was unexpected because ACTH is the primary regulator of cortisol secretion by the adrenal glands (Lightman et al., 2020), and previous research demonstrates that the weaning process causes an ACTH-mediated increase in basal cortisol levels (Perremans et al., 2001; Kanitz et al., 2002). Although specific reasons for the lack of weaning and transport-related ACTH differences in the present study are unclear, blood collection timing may be partly responsible. This is because blood was only collected prior to transport and 12 h after the start of transport in the present study, whereas the aforementioned reports (Perremans et al., 2001; Kanitz et al., 2002) collected blood samples immediately after the stressor (e.g., weaning) was initiated. Nevertheless, the overall decrease in circulating cortisol demonstrates that the CRFA was effective in reducing biomarkers of the physiological stress response in weaned and transported pigs.

Stress-induced immune system alterations have been previously described in pigs (Ayala et al., 2012; Hart, 2012; Escribano et al., 2015; Johnson et al., 2020). However, inconsistencies within the literature exist, with some reporting increases in immune biomarkers including IgA, IL-8, IL-1β, and LPS (Johnson, 1998; Karrow, 2006; Annamalai et al., 2015; Wyns et al., 2015), and others reporting reductions in immune biomarkers (e.g., IL-8, IL-1β) during stressful events (Tian et al., 2014). Additionally, the type and timing of the stressor has demonstrated contradictory results where cytokines (i.e., IL-1β, TNFα, and IL-6) have been increased (Johnson et al., 2002) and decreased (Goujon et al., 1995). These inconsistencies may be due to the type, duration, and intensity of the stressor or the detection method (Sorrells et al., 2009). In the present study, circulating IL-8 and IgA levels tended to be greater 12 h Post-T versus Pre-T, while circulating LPS was reduced and IL-1β tended to be reduced in pigs 12 h Post-T versus Pre-T. In the present study, the stressor was classified as “acute” because the stressor was hours versus weeks or months which is classified as “chronic” (Sorrells et al., 2009; Martínez-Miró et al., 2016) and may have augmented the response to the immune biomarkers.

During weaning and transport, feed withdrawal causes pigs to enter a state of negative energy balance (Salfen et al., 2003; Govoni et al., 2005; Inoue et al., 2005). This results in hypoglycemia that causes a drop in insulin (a potent anabolic hormone) resulting in gluconeogenesis in the liver to restore homeostatic levels of circulating glucose as well as lipolysis, which causes the release of NEFAs into circulation (Qaid and Abdelrahman, 2016). Additionally, glucocorticoids play a role in the release of stored glucose by promoting gluconeogenesis in the liver during times of low energy intake (Kuo et al., 2015). In the present study, circulating glucose and insulin were reduced and NEFAs were greater in pigs 12 h Post-T versus Pre-T. This response was likely due to the fact that weaned and transported pigs had feed withdrawn for >12 h resulting in a negative energy balance as previously described (Salfen et al., 2003; Govoni et al., 2005; Inoue et al., 2005). Additionally, circulating insulin tended to be reduced in CRFA when compared to SAL pigs. Because the CRFA treatment reduced circulating cortisol levels in the present study, and glucocorticoids cause the release of stored glucose from the liver (Kuo et al., 2015), this may explain the greater drop in circulating insulin for CRFA pigs. It is possible that CRFA pigs were more hypoglycemic throughout the weaning and transport process due to a reduced ability to mobilize energy stores resulting from inhibited cortisol release. However, these results should be interpreted with caution considering that only a numerical reduction in circulating glucose was observed for CRFA versus SAL pigs 12 h Post-T in the present study.

During periods of stress, glucagon is elevated (Yamada et al., 1993) and the production of glucose, the primary energy source for activated immune cells, is stimulated (Boden et al., 1993). As energy requirements increase, adipose tissue breaks down, and in turn, NEFAs are released into the blood (Adewuyi et al., 2005). Elevated levels of circulating NEFA are an indicator of negative energy balance as observed in dairy cattle (Bell, 1995; Herdt, 1997; Drackley, 1999). In the present study, circulating insulin tended to be reduced in CRFA pigs when compared to SAL. Overall, glucose and insulin were reduced and NEFAs were greater in pigs 12 h Post-T versus Pre-T in the present study. Literature has shown that fasting reduces insulin and glucose levels (Pollitt et al., 1982; Moebus et al., 2011) and elevates NEFA levels (Il’yasova et al., 2010). Therefore, reductions in glucose and insulin 12 h Post T was expected as pigs did not have access to feed or water during the weaning and transport process. Furthermore, previous research has demonstrated that CRF administration elevates circulating insulin levels (Genuth and Lebovitz, 1965). Therefore, by blocking CRF receptors in the present study, it was expected that insulin would be reduced in CRFA pigs and this was confirmed by the results.

Although no studies to our knowledge have reported reductive effects of Astressin B on circulating ACTH >24 h post-administration, ACTH tended to be reduced in CRFA versus SAL pigs during the dietary treatment phase in the present study, regardless of post-weaning and transport dietary treatment. However, the biological significance of this reduction is unknown and is likely minimal considering that no corresponding dietary treatment phase cortisol differences were observed between CRFA and SAL pigs. Despite the lack of dietary treatment-related circulating stress hormone differences, on d 7, jejunal CRF mRNA abundance tended to be reduced in AB-fed pigs when compared to NAB-fed pigs and tended to be decreased in CRFA versus SAL pigs. While details on the mode of action for peripheral CRF signaling remains unclear, it has been shown that stress affects the expression of CRF signaling in the gastrointestinal tract (Taché and Perdue, 2004; Larauche et al., 2009a). Reduced CRF mRNA abundance in the intestine is generally associated with a decreased stress response (Larauche et al., 2009b) and this may indicate that both AB-fed pigs and CRFA pigs were undergoing less stress when compared to NAB and SAL pigs at d 7 post-weaning and transport.

Despite the tendency for reduced jejunal CRF mRNA abundance for AB-fed pigs on d 7, the ileal mRNA abundance of CRF, CRFR1, and CRFR2 tended to be greater on d 14 in AB-fed pigs when compared to NAB-fed pigs, regardless of CRFA treatment. Additionally, CRFR2 mRNA abundance was greater in CRFA pigs fed the AB diet versus SAL pigs fed the NAB diet on d 14. Increased mRNA abundance of intestinal CRFR1 may be associated with stress-induced intestinal dysfunction (Taché et al., 2004; Larauche et al., 2008) while increased intestinal CRFR2 mRNA abundance may produce negative gastrointestinal inflammatory responses (Kokkotou et al., 2006). To our knowledge, no other studies have measured intestinal CRF, CRFR1, or CRFR2 mRNA abundance differences related to AB or CRFA administration in pigs. However, greater CRF, CRFR1, and CRFR2 mRNA and protein abundance has been observed in the jejunum of pigs 24 h after weaning stress (Moeser et al., 2007b; Smith et al., 2010; Wang et al., 2015) and this many indicate that AB-fed pigs and CRFA pigs given AB in the present study were undergoing greater stress on d 14 post-weaning and transport. However, these data should be interpreted with caution because no other corresponding physiological observations were associated with greater stress during the dietary treatment phase in AB-fed or CRFA administered pigs.

Transepithelial resistance is a measure commonly used to determine intestinal permeability with increased permeability associated with a decrease in TER (Hu et al., 2013). In the present study, no treatment related TER differences were detected at d 7 or 14 post-weaning and transport. The lack of CRFA-related TER differences conflicts with a previous report indicating that intraperitoneal CRFA administration at the same dose (30 ug/kg) results in increased TER in weaned pigs (Smith et al., 2010). However, this discrepancy may be related to the timing of TER testing in the present study as the aforementioned experiment (Smith et al., 2010) measured TER within 24 h of CRFA administration. As such, it is possible that had TER been measured within 24 h of CRFA administration in the present study, differences would have been detected. As for the lack for AB effects, no data to our knowledge are available on the direct effects of AB administration on TER in weaned pigs. However, data from the present study may suggest that AB administration does not directly impact TER, at least when measured on d 7 and 14 post-administration.

Change in short circuit current, also known as dIsc, is used to determine the active transport of substances (i.e., ions, nutrients, and drugs) through epithelial cells (Clarke, 2009), and glucose transport was evaluated following weaning and transport in the current study. In general, weaning is associated with social and environmental stress and has been shown to compromise sodium-glucose co-transporter function resulting in reduced glucose transport (Boudry et al., 2004; Li et al., 2017). It has been hypothesized that the reduction in glucose transport is mediated by the CRF signaling pathways (Li et al., 2017). As such, it would be expected that blocking CRF signaling would improve glucose active transport. Contrary to this hypothesis, glucose dIsc was reduced on d 14 by CRFA relative to SAL administration in the present study. These data may suggest that glucose active transport was inhibited by CRFA administration. However, it is important to note that this difference was only observed 14-d post-CRFA administration and thus, it is currently unclear whether this effect was directly related to an inhibition of CRFA signaling. Despite this, it appears that the inclusion of AB in the diets of weaned pigs improved glucose active transport on d 7 as indicated by a tendency for an increase in dIsc for CRFA pigs fed AB when compared to CRFA pigs fed NAB. These data may indicate that AB can play a role in improving glucose active transport in the intestine of weaned pigs, which has positive implications for nutrient uptake. However, because only a tendency was observed these data should be interpreted with caution.

The intestinal barrier consists of an epithelial cell layer joined together by tight junction proteins (Kim et al., 2012; Li et al., 2012). These proteins (i.e., ZO-1, CLAD, and OCL) regulate the leakiness of the epithelium by changing the ion and pore size (van Itallie and Anderson, 2004). Zonula occludin proteins interact directly with OCL and CLAD to regulate the assembly of the intestinal barrier (Schneeberger and Lynch, 2004; Marchiando et al., 2010). Previous studies have demonstrated that weaning stress leads to decreased jejunal OCL and CLAD protein abundance while jejunal ZO-1 protein expression is not affected (Wang et al., 2015). Other studies (Xun et al., 2018) demonstrated that jejunal OCL and ZO-1 and ileal OCL, ZO-1, and CLAD mRNA abundance is greater in less stressed late weaned versus more stressed early weaned pigs. In the present study, on d 7, CRFA pigs fed AB tended to have greater jejunal ZO-1 and reduced jejunal CLAD mRNA abundance when compared to SAL pigs fed NAB, and CRFA pigs fed NAB tended to have greater ileal CLAD when compared to SAL pigs fed AB. In addition, an overall diet treatment effect was observed whereby AB fed pigs had reduced jejunal CLAD and tended to have greater ileal OCL mRNA abundance when compared to NAB pigs on d 7. In general, these data appear to indicate that the CRFA treatment had a positive impact on tight junction protein mRNA abundance, which may explain the aforementioned reduction in Isc as an indicator of reduced intestinal permeability. To our knowledge, this is the first time that CLAD or OCL mRNA abundance differences directly related to AB administration have been observed in newly weaned and transported pigs as most studies in pigs have observed no effects (Tan et al., 2019; McConn et al., 2020; Ruckman et al., 2020; Duttlinger et al., 2021). However, research in mice suggests that AB induced disruptions in microbiota may influence intestinal barrier function (Schumann et al., 2005; Tulstrup et al., 2015; Feng et al., 2019), and this may be one mechanism by which AB altered CLAD and OCL mRNA abundance in the present study. It is important to note that while tight junction protein mRNA abundance may explain gene activations, additional research is needed to understand the assembly and structuring of the tight junction proteins.

In addition to tight junction proteins, intestinal growth and enterocyte proliferation also plays a key role in intestinal function. Glucagon-like peptide 2 is a commonly used biomarker of improved intestinal health and growth in pigs (Burrin D. et al., 2003; Burrin et al., 2005). Specifically, GLP-2 plays a role in improving nutrient absorption and gut barrier function (Burrin D. G. et al., 2003; Connor et al., 2015). In the present study, jejunal GLP-2 mRNA abundance was greater in CRFA pigs fed AB when compared to SAL pigs fed NAB on d 14. Previous research (Duttlinger et al., 2021) has demonstrated that jejunal GLP-2 mRNA abundance is increased at the end of the nursery phase in pigs provided AB immediately following weaning and transport. Therefore, it is possible that the increased GLP-2 mRNA abundance observed in the present study was directly related to the AB administration. Although, it should be noted that no GLP-2 mRNA abundance differences were observed for SAL pigs fed AB and so the CRFA treatment may have contributed to the greater GLP-2 mRNA abundance. However, the relative importance of this effect is currently unknown considering that no improvements in intestinal integrity (e.g., Isc) were observed for CRFA pigs fed AB. Additionally, since GLP-2 is produced from enteroendocrine L cells (Drucker and Yusta, 2014), an alternative explanation for the increased GLP-2 mRNA abundance observed in the present study may be directly related to either the number of enteroendocrine L cells present or the amount of GLP-2 produced per enteroendocrine L cell.

Tumor necrosis factor alpha is produced by macrophages during acute inflammation (Idriss and Naismith, 2000) and increased intestinal TNFα mRNA abundance is an indicator of greater intestinal inflammation (Pearce et al., 2014). In the present study, on d 7, ileal TNFα mRNA abundance tended to be reduced in SAL pigs fed NAB when compared to CRFA pigs fed NAB, and, on d 14, jejunal TNFα mRNA abundance was reduced in AB fed pigs versus NAB fed pigs. The effects of CRF on increasing ileal TNFα mRNA abundance in the present study contradict previous reports in in vitro models indicating that CRF increases TNFα leading to greater intestinal permeability (Overman et al., 2012). However, this discrepancy may be explained by response differences between in vitro and in vivo models (Nejdfors et al., 2000). As for the influence of AB on reducing jejunal TNFα mRNA abundance in the present study, these data are supported by other research (McConn et al., 2020) indicating that AB administration following weaning and transport stress decreases jejunal TNFα mRNA abundance in nursery pigs. Additional research in in vivo models is needed to confirm whether CRF signaling influences TNFα production in the intestine of weaned pigs.

Greater VH, reduced CD, and increased VH:CD in the small intestine are commonly reported morphological indicators of improved intestinal health and function (Piva et al., 2001; Feng et al., 2015; Xue et al., 2018). Greater VH and VH:CD ratio are associated with increased nutrient absorption (Piva et al., 2001; Feng et al., 2015) and decreased circulating proinflammatory cytokines (Willing and van Kessel, 2007; Xue et al., 2018). Additionally, reduced CD indicates a decrease in epithelial turnover in the intestine, which is associated with reduced intestinal damage and inflammation (Xue et al., 2018). Unfortunately, these morphological indicators of intestinal health are negatively impacted by weaning stress in pigs (Wang et al., 2015). In the present study, ileal CD was reduced in CRFA pigs when compared to SAL pigs on d 14 and this may have been related to the CRFA treatment blocking CRFR-1 and CRFR-2 since it is known that CRF plays a direct role in negatively impacting morphological markers of intestinal health and function (Moeser et al., 2007a). However, these results should be interpreted with caution as this was the only CRFA effect observed for intestinal morphology and this difference occurred 14 d after the CRFA injection was initially given. Additionally, on d 7, jejunal VH and CD, and ileal VH:CD ratio were greater in pigs fed AB when compared to pigs fed NAB. In general, these data are indicative of a positive benefit of AB on morphological biomarkers of intestinal health. However, it is currently unclear what role AB plays in relation to improvements in morphological indicators of intestinal health and function as variable results are reported in the literature with some studies reporting positive effects of AB on intestinal morphology including increased VH, reduced CD, and a greater VH:CD ratio (Piva et al., 2008; Oliver and Wells, 2013; Duttlinger et al., 2021), and others demonstrating no AB effects (Thymann et al., 2007; Shen et al., 2009; McConn et al., 2020). Therefore, more research should be conducted to identify the mechanism(s) by which AB influence intestinal morphology.

Stress alters immune system biomarkers and these alterations may be associated with greater or reduced levels of physiological stress that are dependent on the stressor type, duration, intensity, and detection method (Reiche et al., 2004; Sorrells et al., 2009). Because the CRFA used in the present study decreases cortisol production, it would be expected that the inhibitory effects of cortisol on pro-inflammatory cytokines would be reduced resulting in an increase in both pro-inflammatory cytokine levels and protective IgA levels as the study progressed (DeRijk et al., 1997; Rohleder et al., 2003; Elenkov, 2004; Salicrú et al., 2007). This hypothesis is supported by an observed overall increase in circulating IL-6 for CRFA pigs versus SAL pigs in the present study. A function of IL-6 is to promote cortisol release which in turn, causes an increase in the production of anti-inflammatory cytokines that act to reduce pro-inflammatory cytokines (Warren et al., 1997; Webel et al., 1997). Because CRFA inhibited cortisol production, this likely resulted in a greater increase in IL-6 due to a lack of feedback (e.g., cortisol release; Williams et al., 2009). As such, the pro-inflammatory cytokine TNFα tended to be greater in CRFA pigs fed AB when compared to SAL pigs fed AB on d 3 and 7, and also tended to be greater in CRFA pigs fed AB when compared to SAL pigs fed NAB on d 7 and 14 in the present study. Additionally, IgA was increased in CRFA pigs fed AB when compared to SAL pigs fed AB on d 7 and was greater in CRFA pigs fed NAB versus SAL pigs fed AB and CRFA pigs fed AB on d 14. This response may be related to the protective anti-inflammatory role IgA plays in the immune response (Mkaddem et al., 2014; Monteiro, 2014) and the aforementioned increase in TNFα for pigs given the CRFA injections. Finally, it was observed that circulating IL-8 was reduced in CRFA pigs fed NAB when compared to SAL pigs fed AB in the present study. This response may be explained by positive relationship between cortisol and neutrophil counts (e.g., increased cortisol = increased neutrophils; Davis et al., 1991). Therefore, because neutrophils are responsible for producing IL-8 (Lin et al., 1994), inhibiting cortisol (and potentially neutrophil counts) may have resulted in the observed decrease in circulating IL-8 for pigs given the CRFA treatment.

Low feed intake is common during the first 2 weeks post-weaning which may negatively impact growth performance (van Dijk et al., 2001). During this stressful time, the immune system is activated which uses a greater amount of energy and nutrients (Lochmiller and Deerenberg, 2000; Johnson, 2012; Kvidera et al., 2017). In the present study, ADG tended to be reduced in CRFA pigs when compared to SAL pigs from d 0–7. One explanation for the reduced growth performance may be related to the increased biomarkers of inflammatory responses observed for CRFA versus SAL pigs in the present study. It is known that circulating cytokines shift the partitioning of nutrients from growth toward the immune system (Johnson, 1998; Buchanan and Johnson, 2007; Kvidera et al., 2017). Therefore, it is possible that more energy was being diverted towards immune activation as opposed to growth in the CRFA versus SAL pigs. However, these results should be interpreted with caution as this study was not specifically designed to identify growth performance related differences related to the treatments due to individual housing of pigs and relatively low pig numbers per treatment to measure growth performance. Therefore, any future studies focused on growth performance measures related to physiological stress should take this into consideration.

The stress response related to weaning and transport has a negative impact on intestinal barrier development in pigs (Moeser et al., 2017). When the stress load imposed by the stressor is not significant (i.e., comfortable transport temperature, greater nursery pen space per pig than commercial conditions), a physiological stress response is not initiated, which may result in a lack of AB differences (McConn et al., 2020). The present study is, to the best of our knowledge, the first to report on the effects of providing a CRFA injection and AB diet to newly weaned and transported pigs. However, some limitations in the current study design should be mentioned. While the current study design was similar to previous research in newly weaned and transported pigs (Duttlinger et al., 2019; McConn et al., 2020), future studies should implement catheters to allow for more frequent blood collections to better characterize the physiological response of the pigs. In addition, the mode of the CRF receptor antagonism likely resulted in unintended downstream responses (i.e., effects on immune parameters) that should be taken into consideration when determining the timing of sample collection. Regardless, results from this study provide new information related to the interactions between the physiological stress response and AB supplementation on gastrointestinal function in pigs that may be helpful in identifying when AB supplementation is most effective or necessary in swine production.

Weaning and transport impact intestinal function and overall pig health and welfare. However, knowledge about how CRF signaling interacts with antibiotics to influence intestinal physiology is limited. Based on previous research, we hypothesized that CRF receptor signaling would mediate weaning and transport-induced intestinal dysfunction under production relevant conditions. In addition, we hypothesized that blocking CRF receptor signaling during the weaning process would improve measures of intestinal function similarly to the administration of commonly provided prophylactic antibiotics following weaning and transport. Results from this study indicated that, in general, CRFA pigs and pigs fed AB had some similar intestinal physiology measures post-weaning and transport. The present study brings insight into the specific mechanisms by which CRF signaling, and antibiotic supplementation may influence the intestinal physiological response in newly weaned pigs.