Regardless of the efforts put into preventing or reducing fungal growth, extensive mycotoxin contamination has been reported in animal feeds. In the case of pigs, one of the mycotoxins of major concern is deoxynivalenol (DON). The use of adsorbents as feed additives represents one of the strategies to control mycotoxins' contamination in feedstuff. Therefore, the aim of the study was to verify the ability of chlorophyllin (CHL) to reduce the absorption rate of DON in swine mucosa explants. Intestine was obtained from routinely slaughtered adult pigs. The mucosa explants were studied by means of Ussing chamber technique. The effect of DON (10 and 30 μg/ml) on mucosa viability and permeability and CHL (100 μg/ml) impact on DON (30 μg/ml) absorption was verified. The results revealed that mucosa explants isolated from adult animals remained unaffected for 90 min in the presence of DON in the lower concentration (10 μg/ml). Mycotoxin in the higher dose (30 μg/ml) increased mucosa permeability (decreased transepithelial electrical resistance value) and enhanced paracellular transport of lucifer yellow and mannitol but did not affect lactate dehydrogenase leakage. The introduction of CHL neither diminished the absorption rate of DON across swine mucosa explants nor prevented the toxic effects of DON on intestine. In conclusion, the results confirm the negative effect of DON on pig jejunum mucosa. However, the toxic effect of DON was observed only when it was used in relatively high doses. A promising adsorbent agent, CHL, failed to reduce the intensity of DON transport across intestine under in vitro conditions.

Eimeriosis, an infection with Eimeria spp. that affects poultry, causes huge economic losses. Silver nanoparticles (AgNPs) have antibacterial and antifungal properties, but their action against Eimeria infection has not yet been elucidated. This study demonstrates the action of AgNPs in the treatment of mice infected with Eimeria papillata. AgNPs were prepared from Zingiber officinale rhizomes. Phytochemical screening by gas chromatography-mass spectrometry analysis (GC-MS) was used to detect active compounds. Mice were divided into five groups: uninfected mice, uninfected mice that were administered AgNPs, untreated mice infected with 103 sporulated oocysts of E. papillata, infected mice treated with AgNPs, and infected mice treated with amprolium. Characterization of the samples showed the AgNPs to have nanoscale sizes and aspherical shape. Phytochemical screening by GC-MS demonstrated the presence of 38 phytochemical compounds in the extract of Z. officinale. Mice infected with E. papillata-sporulated oocysts were observed to have many histopathological damages in the jejuna, including a decrease in the goblet cell numbers affecting the jejunal mucosa. Additionally, an increased oocyst output was also observed. The treatment of infected mice with AgNPs resulted in the improvement of the jejunal mucosa, increase in the number of goblet cell, and decrease in the number of meronts, gamonts, and developing oocysts in the jejuna. Moreover, AgNPs also led to decreased oocyst shedding in feces. The results revealed AgNPs to have an anticoccidial effect in the jejunum of E. papillata-infected mice and, thus, could be a potential treatment for eimeriosis.

With its abundance of neurons and immunocytes, the gut is a potentially important site for the study of the interaction between the nervous and immune systems. Using immunohistochemical techniques, we tested the hypothesis that gut-associated lymphoid tissue in the porcine small intestine might receive catecholaminergic, cholinergic and peptidergic innervation. Antibodies against protein gene product (PGP) 9.5 were employed to detect neuronal membranes; antibodies against tyrosine hydroxylase (TH), type 2 vesicular monoamine transporter (VMAT-2) and choline acetyltransferase (ChAT) were used to detect catecholaminergic and cholinergic neurons; and antibodies to neuromedin U-8 (NMU-8), substance P (SP) and vasoactive intestinal peptide (VIP) were also used. PGP9.5-immunoreactive nerve fibers were observed between jejunal Peyer's patch (PP) follicles and in submucosal ganglia localized at the base of continuous ileal PP. Many ChAT-positive and a few TH-/VMAT-2-immunoreactive neurons or axons adjacent to jejunal and ileal PP were observed. Neurons and fibers from ganglia situated between or at the base of PP follicles manifested robust immunoreactivities to VIP and NMU-8; relatively less SP immunoreactivity was observed at these locations. All neuromedin-U 8-positive neurons observed exhibited immunoreactivity to ChAT as did some VIP-positive neurons. The specific chemical coding of enteric neurons in close apposition to jejunal and ileal PP and the differential localization of neuropeptides within the jejunal and ileal PP are indicative of neuroimmunomodulation at these sites.

Neuronal abnormalities have been described in the intestine of helminth-infected rats. However, the physiological ramifications of these changes have not been determined. Here, we examined epithelial ion secretion, indicated by increases in short-circuit current (Isc), evoked by electrical transmural stimulation (TS) of enteric nerves in Ussing-chambered jejunal tissues from Nippostrongylus brasiliensis-infected rats. Rats were examined at 10 and 35 days post-infection (p.i.); non-infected rats served as controls. TS resulted in significantly reduced ion secretion in jejunum from 10 day p.i. rats compared to controls or jejunum from 35 day p.i. rats. The TS response in tissue from infected rats had, unlike controls, no cholinergic component. Tissues from both non-infected and infected rats were equally responsive to the muscarinic agonist bethanechol, suggesting that the cholinergic defect was neuronal and not an inability of the epithelium to respond to cholinergic stimulation. However, increases in Isc evoked by exogenous substance P (SP) in tissue from rats 10 day p.i. were reduced in magnitude to approximately 25% of control values. Concomitant with these physiological changes, tissue from infected rats contained increased amounts of substance P immunoreactivity and intestinal sections displayed increased numbers of substance P-immunoreactive nerve fibre profiles at both 10 and 35 days p.i. Thus, following N. brasiliensis infection there is a shift in the enteric nervous system away from cholinergic to non-cholinergic regulation, associated with increased amounts of the pro-inflammatory neuropeptide, substance P. We speculate that changes in neuronal structure and function are intimately involved in the co-ordinated multicellular response to intestinal parasitic infection and subsequent gut recovery.

The aim of this study was to identify transcription factors/regulators that play a crucial role in steering the (innate) immune response shortly (within a few hours) after the first contact of the intestinal mucosa with an inflammatory mediator, and to test whether the processes regulated by these factors/regulators can be modulated by chemical substances of natural origin.

Ileocecal resection (ICR) is a commonly required surgical intervention in unmanageable Crohn's disease and necrotizing enterocolitis. However, the impact of ICR, and the concomitant doses of antibiotic routinely given with ICR, on the intestinal commensal microbiota has not been determined. In this study, wild-type C57BL6 mice were subjected to ICR and concomitant single intraperitoneal antibiotic injection. Intestinal lumen contents were collected from jejunum and colon at 7, 14, and 28 days after resection and compared to non-ICR controls. Samples were analyzed by 16S rRNA gene pyrosequencing and quantitative PCR. The intestinal microbiota was altered by 7 days after ICR and accompanying antibiotic treatment, with decreased diversity in the colon. Phylogenetic diversity (PD) decreased from 11.8 ± 1.8 in non-ICR controls to 5.9 ± 0.5 in 7-day post-ICR samples. There were also minor effects in the jejunum where PD values decreased from 8.3 ± 0.4 to 7.5 ± 1.4. PCoA analysis indicated that bacterial populations 28 days post-ICR differed significantly from non-ICR controls. Moreover, colon and jejunum bacterial populations were remarkably similar 28 days after resection, whereas the initial communities differed markedly. Firmicutes and Bacteroidetes were the predominant phyla in jejunum and colon before ICR; however, Firmicutes became the vastly predominant phylum in jejunum and colon 28 days after ICR. Although the microbiota returned towards a homeostatic state, with re-establishment of Firmicutes as the predominant phylum, we did not detect Bacteroidetes in the colon 28 days after ICR. In the jejunum Bacteroidetes was detected at a 0.01% abundance after this time period. The changes in jejunal and colonic microbiota induced by ICR and concomitant antibiotic injection may therefore be considered as potential regulators of post-surgical adaptive growth or function, and in a setting of active IBD, potential contributors to post-surgical pathophysiology of disease recurrence.

The involvement of renin-angiotensin system in the modulation of gut motility and age-related changes in mRNA expression of angiotensin (Ang II) receptors (ATR) are well accepted. We aimed to characterize, in vitro, the contractile responses induced by Ang II, in jejunum from young (3-6 weeks old) and old rats (≥ 1 year old), to evaluate possible functional differences associated to changes in receptor expression. Mechanical responses to Ang II were examined in vitro as changes in isometric tension. ATR expression was assessed by qRT-PCR. Ang II induced a contractile effect, antagonized by losartan, AT1R antagonist, and increased by PD123319, AT2R antagonist, as well by neural blocker ω-conotoxin and by nitric oxide (NO) synthase inhibitor. No difference in the response was observed between young and old groups. AT1 receptor-mediated contractile response was decreased by U-73122, phospholipase C (PLC) inhibitor; or 2-aminoethoxy-diphenylborate (2-APB), inositol triphosphate (IP3) receptor inhibitor; or nifedipine, L-type calcium channel blocker. Age-related changes in the expression of both AT1 receptor subtypes, AT1a and AT1b, and of AT2 receptors were detected. In conclusion, Ang II modulates the spontaneous contractility of rat jejunum via postjunctional AT1 receptors, involving Ca2+ mobilization from intracellular stores, via PLC/IP3 pathway, and Ca2+ influx from extracellular space, via L-type channels. Prejunctional AT2 receptors would counteract AT1 receptor effects, via NO synthesis. The observed age-related differences in the expression of all AT receptor subtypes are not reflected in the muscular contractile response to Ang II.

1. This study was performed to elucidate the type of afferents that mediate the multiple actions of 5-hydroxytryptamine (5-HT) on mesenteric nerve discharge. Electrophysiological recordings were made from mesenteric afferents innervating the mid-jejunum of the urethane-anaesthetized rat. The discharge of single nerves within the whole nerve recording was monitored using waveform discrimination software. 2. Afferents responded to 5-HT in one of two ways: a short latency, transient excitation mediated by 5-HT3 receptors, or a delayed onset, more prolonged effect that was 5-HT2A receptor mediated. Afferents showing the 5-HT3-mediated response did not respond to luminal distension but were sensitive to intraluminal hydrochloric acid (150 mM) in twenty-eight of twenty-nine experiments. In eight experiments, the 5-HT3-mediated response was reversibly abolished by a 2 min exposure to intraluminal application of local anaesthetic (2 % Xylocaine). 3. Mechanosensitive afferents which responded to distension (< 10 cmH2O) did not show a 5-HT3-mediated response (P = 0.92, n = 14), and maintained this mechanosensitivity after luminal anaesthesia. Mechanosensitive afferents did show a secondary response to 5-HT that was significantly attenuated by atropine (100-200 microg kg-1), whereas hexamethonium (8 mg kg-1) had no effect. 4. In animals whose vagal afferent contribution to their mesenteric nerves had been eliminated by chronic truncal vagotomy, the 5-HT3-mediated response was absent in thirty-six of thirty-six nerve bundles. In contrast, mechanosensitivity to distension and the secondary response to 5-HT could still be evoked. 5. These results suggest that 5-HT stimulates mesenteric afferents by a direct action on 5-HT3 receptors that are present on vagal mucosal afferent terminals. The mucosal afferent response to luminal acid, however, was unaffected by treatment with granisetron (0.5 mg kg-1) indicating that endogenous 5-HT from enterochromaffin cells is not essential for transduction of this luminal signal. In contrast, mechanosensitivity in non-vagal afferents was modulated by 5-HT following an intestinal motor response which was influenced by cholinergic tone.

Enterotoxigenic Escherichia coli (ETEC) is a common cause of diarrhea in humans and livestock. In this study, isobaric tags for relative and absolute quantitation (iTRAQ) combined with multidimensional liquid chromatography (LC) and MS analysis was used for screening the differentially expressed proteins in piglet jejunum after ETEC infection. Totally 1,897 proteins were identified with quantitative information in piglet jejunum. We identified 92 differentially expressed proteins in ETEC-induced diarrhea, of which 30 were up regulated and 62 down regulated. Most of the differentially expressed proteins were involved in intestinal function of binding, metabolic process, catalytic activity and immune responses. The inhibition of intestinal immune responses in the jejunum in ETEC-induced diarrhea was also validated by immunobloting and RT-PCR. Our study is the first attempt to analyze the protein profile of ETEC-infected piglets by quantitative proteomics, and our findings could provide valuable information with respect to better understanding the host response to ETEC infection.

Nanomedicine has recently emerged as a better option for the treatment of various diseases. Here, we investigated the in vivo anticoccidial properties of zinc oxide nanoparticles (ZNPs). ZNPs were crystalline in nature, with a smooth and spherical surface and a diameter in the range of ~10-15 nm. The X-ray diffraction pattern was utilized to identify the crystalline property of the grown ZNPs, whereas field emission scanning electron microscopy was employed to check the size and morphology of the ZNPs. The data showed that mice infected with Eimeria papillata produced 29.7×10(3)±1,500 oocysts/g feces on day 5 postinfection. This output was significantly decreased, to 12.5×10(3)±1,000 oocysts, in mice treated with ZNPs. Infection also induced inflammation and injury of the jejunum. This was evidenced (1) through an increase in the inflammatory histological score, (2) through increased production of nitric oxide and malondialdehyde, and (3) through a decrease in both the glutathione level and goblet cell number in mice jejuna. All these infection-induced parameters were significantly altered during treatment with ZNPs. Our results indicate, therefore, that ZNPs have protective effects against E. papillata-induced coccidiosis.

Acute sympathetic denervation of the small intestine up-regulates alpha1-adrenoceptors on villus enterocytes and activation of these alpha1-adrenoceptors inhibits chloride secretion. We tested whether alpha1-adrenoceptor-mediated inhibition of chloride secretion was the result of reduced ClC-2 chloride channel expression. Phorbol myristate acetate (PMA) (a protein kinase C (PKC) activator) had no effect on ClC-2 levels. In contrast, alpha1-adrenoceptor activation significantly decreased ClC-2 protein levels in both the villus (1.58+/-0.19 to 0.75+/-0.19 arbitrary units) and crypt (1.69+/-0.15 to 0.37+/-0.23 arbitrary units) epithelial cells from the acutely denervated jejunum but not innervated controls. These data suggest that inhibition of chloride secretion following alpha1-adrenoceptor activation in the acutely denervated small intestine may be through ClC-2 down-regulation.

Somatostatins are proteins that are involved in gastrointestinal function. However, little is known with regard to somatostatin receptor subtype (SSTR) expression changes that occur in the jejunum during low-grade inflammation and during subsequent octreotide treatment. The aim of the present study was to investigate the expression of SSTRs in the jejunums of Cryptosporidium parvum (C. parvum)-infected rats by immunohistochemisty, reverse transcription (RT) PCR and quantitative real-time RT-PCR assays. Five-day-old suckling Sprague-Dawley rats (n = 15 for each group) were orally gavaged with 105 Nouzilly isolate (NoI) oocysts. Rats then received 50 μg/kg/day of octreotide by intraperitoneal injection from day 10 to day 17 post-infection. Animals were sacrificed on days 7 and 14 post-infection for immunohistochemical analysis and on days 14, 35 and 50 for mRNA expression analysis of SSTR subtypes. Histological analysis of jejunum tissues demonstrated infection of C. parvum along the villus brush border on day 7 post-infection and infection clearance by day 14 post-infection. Real-time PCR analysis indicated that in the inflamed jejunum, a significant increase in SSTR1 and SSTR2 expression was observed on day 14 post-infection. Octreotide therapy down-regulated the expression of SSTR2 on day 37 post-infection but significantly increased expression of SSTR1, SSTR2 and SSTR3 on day 50 post-infection. The results indicate that specific SSTRs may regulate the inflammatory pathway in the rat intestinal inflammation model.

Gut microbiota contributes to human health. Plenty of studies demonstrate that antibiotics can disrupt gut ecosystem leading to dysbiosis. Little is known about the microbial variation of appendix and its up/downstream intestine after antibiotic treatment. This study aimed to investigate the microbiome and mucosal morphology of jejunum, appendix, and colon of rats in health and dysbiosis. A rodent model of antibiotic-induced dysbiosis was employed. Microscopy was used to observe mucosal morphological changes. 16S rRNA sequencing was performed for identifying bacterial taxa and microbiome structure. The appendices of dysbiosis were found enlarged and inflated with loose contents. Microscopy revealed the impairment of intestinal epithelial cells. High-throughput sequencing showed the Operational Taxonomic Units changed from 361 ± 33, 634 ± 18, 639 ± 19 in the normal jejunum, appendix, colon to 748 ± 98, 230 ± 11, 253 ± 16 in the disordered segments, respectively. In dysbiosis, Bacteroidetes translocated inversely from the colon and appendix (0.26%, 0.23%) to the jejunum (13.87% ± 0.11%); the relative abundance of all intestinal Enterococcaceae increased, while Lactobacillaceae decreased. Several bacterial clusters were found correlated to the normal appendix, whereas nonspecific clusters correlated to the disordered appendix. In conclusion, species richness and evenness reduced in the disordered appendix and colon; similar microbiome patterns were shared between the appendix and colon regardless of dysbiosis; site-specific bacteria were missing in the disordered appendix. Appendix is likely a transit region involving in upper and lower intestinal microflora modulation. The limitation of this study is all the data were derived from rats. We must be cautious about translating the microbiome results from rats to humans.

Deoxynivalenol (DON), a frequent mycotoxin worldwide, impairs human and animal health. The response of microRNAs, small non-coding RNAs, to DON has been scarcely investigated, but holds remarkable potential for biomarker applications. Hence, we aimed to investigate DON-induced changes in the microRNA expression in porcine liver, jejunum and serum by combining targeted and untargeted analyses. Piglets received uncontaminated feed or feed containing 900 µg/kg and 2500 µg/kg DON for four weeks, followed by a wash-out period. In tissue, only slight changes in microRNA expression were detected, with ssc-miR-10b being downregulated in liver of DON-exposed piglets. In serum, several microRNAs were differentially expressed upon DON exposure, four of which were validated by qPCR (ssc-miR-16, ssc-miR-128, ssc-miR-451, ssc-miR-205). The serum microRNA response to DON increased over time and declined after removal of contaminated diets. Receiver operating curve analyses for individual microRNAs were significant, and a combination of the four microRNAs increased the predictive capacity for DON exposure. Predicted microRNA target genes showed enrichment of several pathways including PIK3-AKT, Wnt/β-catenin, and adherens junctions. This study gives, for the first time, a comprehensive view of the porcine microRNA response to DON, providing a basis for future research on microRNAs as biomarkers for mycotoxins.

The gut microbiome (GMB), comprising the commensal microbial communities located in the gastrointestinal tract, has co-evolved in mammals to perform countless micro-ecosystem services to facilitate physiological functions. Because of the complex inter-relationship between mammals and their gut microbes, the number of studies addressing the role of the GMB on mammalian health is almost exclusively limited to human studies and model organisms. Furthermore, much of our knowledge of wildlife-GMB relationships is based on studies of colonic GMB communities derived from the feces of captive specimens, leaving our understanding of the GMB in wildlife limited. To better understand wildlife-GMB relationships, we engaged hunters as citizen scientists to collect biological samples from legally harvested black bears (Ursus americanus) and used 16S rRNA gene amplicon sequencing to characterize wild black bear GMB communities in the colon and jejunum, two functionally distinct regions of the gastrointestinal tract. We determined that the jejunum and colon of black bears do not harbor significantly different GMB communities: both gastrointestinal sites were dominated by Firmicutes and Proteobacteria. However, a number of bacteria were differentially enriched in each site, with the colon harboring twice as many enriched taxa, primarily from closely related lineages.

Side effects associated with nonsteroidal anti-inflammatory drugs (NSAIDs) treatment are a serious limitation of their use in anti-inflammatory therapy. The negative effects of taking NSAIDs include abdominal pain, indigestion nausea as well as serious complications such as bleeding and perforation. The enteric nervous system is involved in regulation of gastrointestinal functions through the release of neurotransmitters. The present study was designed to determine, for the first time, the changes in pituitary adenylate cyclase-activating polypeptide (PACAP), substance P (SP) and galanin (GAL) expression in porcine jejunum after long-term treatment with aspirin, indomethacin and naproxen. The study was performed on 16 immature pigs. The animals were randomly divided into four experimental groups: control, aspirin, indomethacin and naproxen. Control animals were given empty gelatin capsules, while animals in the test groups received selected NSAIDs for 28 days. Next, animals from each group were euthanized. Frozen sections were prepared from collected jejunum and subjected to double immunofluorescence staining. NSAIDs supplementation caused a significant increase in the population of PACAP-, SP- and GAL-containing enteric neurons in the porcine jejunum. Our results suggest the participation of the selected neurotransmitters in regulatory processes of the gastrointestinal function and may indicate the direct toxic effect of NSAIDs on the ENS neurons.

Cell surface receptor-mediated viral entry plays a critical role in this infection. Well-established SARS-CoV-2 receptors such as ACE2 and TMPRSS2 are highly expressed in the gastrointestinal tract. In fact, there are evidences that SARS-CoV-2 infects epithelial cells from the digestive system. However, emerging research has identified novel mediators such as DPP9, TYK2, and CCR2, all playing a critical role in inflammation. We evaluated the expression of SARS-CoV-2 receptors in peripheral leukocytes (n = 469), jejunum (n = 30), and colon (n = 37) of three independent cohorts by real-time PCR, RNA-sequencing, and microarray transcriptomics. We also performed HPCL-MS/MS lipidomics and metabolomics analyses to identify signatures linked to SARS-CoV-2 receptors. We found markedly higher peripheral leukocytes ACE2 expression levels in women compared to men, whereas the intestinal expression of TMPRSS2 was positively associated with BMI. Consistent lipidomics signatures associated with the expression of these mediators were found in both tissues and peripheral leukocytes involving n-3 long-chain PUFAs and arachidonic acid-derived eicosanoids, which play a key role in the regulation of inflammation and may interfere with viral entry and replication. Medium- and long-chain hydroxy acids, which have shown to interfere in viral replication, were also liked to SARS-CoV2 receptors. Gonadal steroids were also associated with the expression of some of these receptors, even after controlling for sex. The expression of SARS-CoV2 receptors was associated with several metabolic and nutritional traits in different cell types. This information may be useful in the design of potential therapies targeted at coronavirus entry.

Background and Aims: Cholera toxin (CT)-induced hypersecretion requires activation of secretomotor pathways in the enteric nervous system (ENS). AH neurons, which have been identified as a population of intrinsic sensory neurons (ISNs), are a source of excitatory input to the secretomotor pathways. We therefore examined effects of CT in the intestinal lumen on myenteric and submucosal AH neurons. Methods: Isolated segments of guinea pig jejunum were incubated for 90 min with saline plus CT (12.5 μg/ml) or CT + neurotransmitter antagonist, or CT + tetrodotoxin (TTX) in their lumen. After washing CT away, submucosal or myenteric plexus preparations were dissected keeping circumferentially adjacent mucosa intact. Submucosal AH neurons were impaled adjacent to intact mucosa and myenteric AH neurons were impaled adjacent to, more than 5 mm from, and in the absence of intact mucosa. Neuronal excitability was monitored by injecting 500 ms current pulses through the recording electrode. Results: After CT pre-treatment, excitability of myenteric AH neurons adjacent to intact mucosa (n = 29) was greater than that of control neurons (n = 24), but submucosal AH neurons (n = 33, control n = 27) were unaffected. CT also induced excitability increases in myenteric AH neurons impaled distant from the mucosa (n = 6) or in its absence (n = 5). Coincubation with tetrodotoxin or SR142801 (NK3 receptor antagonist), but not SR140333 (NK1 antagonist) or granisetron (5-HT3 receptor antagonist) prevented the increased excitability induced by CT. Increased excitability was associated with a reduction in the characteristic AHP and an increase in the ADP of these neurons, but not a change in the hyperpolarization-activated inward current, Ih . Conclusions: CT increases excitability of myenteric, but not submucosal, AH neurons. This is neurally mediated and depends on NK3, but not 5-HT3 receptors. Therefore, CT may act to amplify the secretomotor response to CT via an increase in the activity of the afferent limb of the enteric reflex circuitry.

The purpose of this study was to explore the effects of curcumin on IUGR jejunum damage. A total of 24 IUGR and 12 normal-birth weight (NBW) female crossbred (Duroc × Landrace × Large White) piglets were randomly assigned into three groups at weaning (26 days): IUGR group, NBW group, and IUGR + CUR group, which were fed diets containing 0 mg/kg (NBW), 0 mg/kg (IUGR) and 200 mg/kg (IUGR + CUR) curcumin from 26 to 115 days of age. Results showed that dietary supplementation with 200 mg/kg curcumin significantly increased the total superoxide dismutase (T-SOD) activity and decreased the malondialdehyde (MDA) content in the jejunum of IUGR pigs (p < 0.05). Results of real-time PCR showed that the IUGR + CUR group significantly increased the gene expression of NF-E2-related factor 2 (Nrf2) (p < 0.05), and increased the glutamate-cysteine ligase catalytic subunit (GCLC), superoxide dismutase 1 (SOD1), glutamate-cysteine ligase modifier subunit (GCLM), and NAD(P)H quinone dehydrogenase 1 (NQO1) mRNA expression compared with the IUGR group (p < 0.05). Western blot results showed that dietary supplementation with 200 mg/kg curcumin significantly increased the protein levels of Nrf2 and NQO1. Compared with the IUGR group, pigs in IUGR + CUR group showed significantly decreased the levels of tumor necrosis factor-α (TNFα), interleukin-6 (IL-6), and interferon gamma (IFNγ) (p < 0.05), and increased the interleukin-2 (IL-2) level (p < 0.05). Dietary supplementation with 200 mg/kg curcumin significantly reduced cysteinyl aspartate specific proteinase 3 (caspase3), BCL2-associated X protein (bax), B-cellCLL/lymphoma 2 (bcl2), and heat-shock protein 70 (hsp70) mRNA expression, and increased occludin (ocln) mRNA expression (p < 0.05). In conclusion, dietary supplementation with 200 mg/kg curcumin can alleviate jejunum damage in IUGR growing pigs, through Nrf2/Keap1 pathway.

Major depressive disorder (MDD) is the leading cause of disability worldwide. Of individuals with MDD, 30% to 50% are unresponsive to common antidepressants, highlighting untapped causal biological mechanisms. Dysfunction in the microbiota-gut-brain axis has been implicated in MDD pathogenesis. Exposure to chronic stress disrupts blood-brain barrier integrity; still, little is known about intestinal barrier function in these conditions, particularly for the small intestine, where absorption of most foods and drugs takes place.