Development Of Small Intestine Research Articles

PSIV-A-7 Effects of late gestational nutrient restriction of beef heifers on small intestinal crypt depth in neonatal calves

Abstract We hypothesized that late gestational nutrient restriction would impair small intestinal development in neonatal calves, including crypt cell depth and proliferation. Fall-calving crossbred beef heifers [body weight (BW) = 466 ± 30 (SD) kg; BCS: 5.4 ± 0.5] bred to a single sire were individually-fed 100% (control; n = 10) or 70% (nutrient restricted; n = 12) of NASEM metabolizable energy and metabolizable protein requirements for maintenance, pregnancy, and growth from d 160 of gestation to calving. Calves were removed from their dams immediately post-calving and fed artificial colostrum and milk replacer relative to body weight until euthanasia at 48.7 ± 0.4 h of age. The gastrointestinal tract was removed, and proximal jejunum samples were dissected from each calf and immersion-fixed in 10% neutral buffered formalin. Tissues were embedded in paraffin blocks and cut into 5-µm sections that were mounted on glass slides. Slides were incubated with Ki-67 (marker of nuclear proliferation) and counterstained with Hematoxylin using an autostainer. Images were taken at 5× magnification using an upright microscope. QuPath software was used to measure crypt depth, starting at the base of the crypt region and ending at the furthest cluster of Ki-67 positive cells, perpendicular to the base of the mucosa. For each calf, 10 crypt depth measurements were taken from 4 images, resulting in 40 crypt depth measurements that were averaged. Nutritional plane was a fixed effect in the model, and maternal sire, date of study initiation, and calf sex (when P < 0.25) were considered covariates. We previously reported that calves born to nutrient restricted dams weighed less (P ≤ 0.05) at birth and 48 h than calves born to control dams. Small intestinal mass tended to be less (P = 0.11) in offspring of nutrient restricted dams but was not affected (P = 0.58) when expressed relative to body weight. Calves born to nutrient restricted dams also tended to have less (P = 0.11) small intestinal mass relative to brain weight. Maternal nutrient restriction did not affect (P = 0.95) jejunal crypt depth. Additionally, crypt depth relative to body weight was not affected (P = 0.20) by nutrient restriction. Although crypt depth was not affected, further analysis of proliferation and morphology will help to understand the relationship between maternal nutrient restriction and small intestine development in neonatal calves.

Effects of tributyrin supplementation in calf starter on growth, blood parameters and development of rumen and small intestine in Holstein calves fed milk replacers with different fatty acid profile

The objective of this study was to evaluate the effects of tributyrin (TB) supplementation in calf starter on development of the rumen and small intestine for calves fed two milk replacers differing in fatty acid composition. Fifty-four Holstein calves (38 heifers and 16 bull calves) were assigned to one of the four treatments: (1) milk replacer containing 31 g/kg C8:0 and 29 g/kg C10:0 in total fatty acids (MR-) and calf starter without TB (ST-) (MR-ST-; n = 14), (2) MR- and calf starter with a TB supplement (600 g/kg TB and 400 g/kg silicon dioxide) at 6 g/kg of DM (ST+) (MR-ST+; n = 13), (3) milk replacer containing 26 g/kg C4:0, 57 g/kg C8:0, and 56 g/kg C10:0 in total fatty acids (MR+) and ST- (MR+ST-; n = 13), and (4) MR+ and ST+ (MR+ST+; n = 14). Milk replacers were offered at 600 g/d (powder basis) from 8 to 14 d, increased up to 1300 g/d from 15 to 21 d, 1400 g/d from 22 to 49 d, decreased down to 700 g/d from 50 to 56 d, and 600 g/d from 57 to 63 d, and then weaned at 64 d of age. Data and samples were collected until 91 d of age. All the calves were fed one of the calf starters and chopped hay ad libitum from 8 d of age. Bull calves were euthanized at weaning to determine weights of digestive organs and evaluate ruminal and small intestinal morphology. Calf starter and milk replacer treatments did not affect dry matter intake, growth performance, digestive organs weights (kg/100 kg of body weight), and rumen papillae length. However, calves fed ST+ had greater ratio of villus height to crypt depth (2.20 vs. 1.84; P < 0.01) in the ileum compared to those fed ST-. In addition, calves fed MR+ had less crypt depth (240 vs. 298 µm; P = 0.02) and greater ratio of villus height to crypt depth (2.22 vs. 1.91; P < 0.01) in the ileum compared to those fed MR-. A tendency for interaction between milk replacer and calf starter treatments was observed for the ratio of villus height to crypt depth in the jejunum, in which TB in calf starter increased the ratio only for calves fed MR-. Milk replacer treatment did not affect plasma glucagon-like peptide-2 (GLP-2) concentration. However, calves fed ST+ had greater plasma GLP-2 concentration compared to those fed ST- after weaning (1.16 vs. 0.80 ng/mL; P < 0.02). These results suggest that TB supplementation for dairy calves may affect small intestinal morphology at weaning, and increase plasma GLP-2 concentration after weaning.

Sodium butyrate administration improves intestinal development of suckling lambs.

This study was conducted to investigate the effects of sodium butyrate (SB) supplementation on growth performance, intestinal barrier functions, and intestinal bacterial communities in sucking lambs. Forty lambs of 7 d old, with an average body weight (BW) of 4.46 ± 0.45kg, were allocated into the control (CON) or SB group, with each group having five replicate pens (n = 5). Lambs were orally administered SB at 1.8mL/kg BW in the SB group or the same volume of saline in the CON group. Treatments were administered from 7 to 35 d of age, when one lamb from each replicate was slaughtered to obtain intestinal tissues and contents. The results showed that supplementation with SB tended to increase the BW (P = 0.079) and the starter intake (P = 0.089) of lambs at 35 d of age. The average daily gain of lambs in the SB group was significantly greater than that in the CON group (P < 0.05). The villus height of jejunum in the SB group was markedly higher (P < 0.05) than that in the CON group. In ileum, lambs in the SB group had lower (P < 0.05) crypt depth and greater (P < 0.05) villus-to-crypt ratio than those in the CON group. Compared with the CON group, the mRNA and protein expressions of Claudin-1 and Occludin were increased (P < 0.05) in the SB group. Supplementation with SB decreased the relative abundances of pathogenic bacteria, including Clostridia_UCG-014 (P = 0.094) and Romboutsia (P < 0.05), which were negatively associated with the intestinal barrier function genes (P < 0.05). The relative abundance of Succiniclasticum (P < 0.05) was higher in the SB group, and it was positively correlated with the ratio of villi height to crypt depth in the jejunum (P < 0.05). Compared with the CON group, the function "Metabolism of Cofactors and Vitamins" was increased in the SB group lambs (P < 0.05). In conclusion, SB orally administration during suckling period could improve the small intestine development and growth performance of lambs by inhibiting the harmful bacteria (Clostridia_UCG-014, Romboutsia) colonization, and enhancing intestinal barrier functions.

Acute and persistent effects of oral glutamine supplementation on growth, cellular proliferation, and tight junction protein transcript abundance in jejunal tissue of low and normal birthweight pre-weaning piglets.

Breeding for higher fertility has resulted in a higher number of low birthweight (LBW) piglets. It has been shown that LBW piglets grow slower than normal birthweight (NBW) littermates. Differences in growth performance have been associated with impaired small intestinal development. In suckling and weaning piglets, glutamine (Gln) supplementation has been associated with improved growth and intestinal development. This study was designed to examine the effects of oral Gln supplementation on growth and small intestinal parameters in LBW and NBW suckling piglets. At birth (day 0), a total of 72 LBW (1.10 ± 0.06 kg) and 72 NBW (1.51 ± 0.06) male piglets were selected. At day 1, litters were standardized to 12 piglets, and experimental piglets supplemented daily with either Gln (1 g/kg BW) or isonitrogenous amounts of Alanine (Ala) as control (1.22 g/kg BW) until day 12. Creep feed was offered from day 14 onward. Subgroups of piglets were euthanized at days 5, 12, and 26 for the analyses of jejunal morphometry, cellular proliferation, glutathione concentration and transcript abundance of tight junction proteins. From age day 11 to 21, Gln supplemented LBW (LBW-Gln) piglets were heavier than Ala supplemented LBW (LBW-Ala) littermates (P = 0.034), while NBW piglets were heavier until age day 26 compared to LBW littermates. Villus height was higher in LBW-Gln compared to LBW-Ala on age day 12 (P = 0.031). Sporadic differences among supplementation and birthweight groups were detected for jejunal cellular proliferation, cellular population and glutathione concentration, whereas age was the most dominant factor. These results show that Gln supplementation improved the growth of LBW piglets compared to LBW-Ala beyond the termination of Gln supplementation, but this was not associated with consistent effects on selected parameters of jejunal development.

Effects of Different Feeding Frequencies on Broiler Chickens’ Growth Performance and Intestinal Villus Development

This experiment was conducted to determine the effects of feeding frequency on growth performance and development of small intestine in broiler chickens from 1 to 14 days of age. Forty Aber acres broiler chicks at 1 day old were randomly assigned to 4 treatments as follows - T1: feeding once daily (100 % diet at 6:30), T2: feeding twice daily (50 % diet at 6:30 and 18:30), T3: feeding 4 times per day (25 % diet at 6:30, 11:30, 16:30 and 21:30) and T4: feeding 6 times per day (16.67 % diet at 6:30, 9:30, 12:30, 15:30, 18:30 and 21:30). Chickens were fed with commercial broiler rations for 14 days. Growth performance parameters including BW, BW gain, FI and FCR were determined. Changes in intestinal villus morphology were examined by hematoxylin and eosin (H&amp;E) dye staining. Results showed that chickens fed 4 and 6 times per day had lower (p &lt; 0.05) BW, BW gain and FI when compared with chickens fed once daily, from 1 to 7 days of age. However, at 14 days of age, there were no significant differences in all parameters of growth performance. There were no changes in gross anatomy of the small intestine. Fixed feeding 4 and 6 times per day resulted in the villus height of the jejunum and ileum being higher (p &lt; 0.05) than when feeding once a day. Feeding 6 times per day resulted in the highest villus density in jejunum among feed regimes. The results suggested that both once and multiple daily feedings were suitable approaches to achieve optimum growth performance for broiler chickens from 1 to 14 days of age. Fixed feeding 6 times per day being the most beneficial for improving intestinal villus development. HIGHLIGHTS Feeding frequency is one of feed restriction method in broilers management From 1 to 7 days of age feeding fed 4 and 6 times per day show lower growth performance than feeding once daily, but not for 14 days of age Fixed feeding 4 and 6 times per day present the villus height at jejunum and ileum higher than feeding once daily Fixed feeding 6 times per day is the most effective solution for enhancing intestinal villus development Here, the experiment demonstrates for the first time that the compensatory growth effects by frequently feeding is at least mediated through adaptation of villus morphology in the small intestine along with improved feed consumption GRAPHICAL ABSTRACT

Integrative genome-scale analyses reveal post-transcriptional signatures of early human small intestinal development in a directed differentiation organoid model

BackgroundMicroRNAs (miRNAs) are important post-transcriptional gene regulators controlling cellular lineage specification and differentiation during embryonic development, including the gastrointestinal system. However, miRNA-mediated regulatory mechanisms involved in early embryonic development of human small intestine (SI) remains underexplored. To explore candidate roles for miRNAs in prenatal SI lineage specification in humans, we used a multi-omic analysis strategy in a directed differentiation model that programs human pluripotent stem cells toward the SI lineage.ResultsWe leveraged small RNA-seq to define the changing miRNA landscape, and integrated chromatin run-on sequencing (ChRO-seq) and RNA-seq to define genes subject to significant post-transcriptional regulation across the different stages of differentiation. Small RNA-seq profiling revealed temporal dynamics of miRNA signatures across different developmental events of the model, including definitive endoderm formation, SI lineage specification and SI regional patterning. Our multi-omic, integrative analyses showed further that the elevation of miR-182 and reduction of miR-375 are key events during SI lineage specification. We demonstrated that loss of miR-182 leads to an increase in the foregut master marker SOX2. We also used single-cell analyses in murine adult intestinal crypts to support a life-long role for miR-375 in the regulation of Zfp36l2. Finally, we uncovered opposing roles of SMAD4 and WNT signaling in regulating miR-375 expression during SI lineage specification. Beyond the mechanisms highlighted in this study, we also present a web-based application for exploration of post-transcriptional regulation and miRNA-mediated control in the context of early human SI development.ConclusionThe present study uncovers a novel facet of miRNAs in regulating prenatal SI development. We leveraged multi-omic, systems biology approaches to discover candidate miRNA regulators associated with early SI developmental events in a human organoid model. In this study, we highlighted miRNA-mediated post-transcriptional regulation relevant to the event of SI lineage specification. The candidate miRNA regulators that we identified for the other stages of SI development also warrant detailed characterization in the future.

Intestinal-specific Hdac3 deletion increases susceptibility to colitis and small intestinal tumour development in mice fed a high fat diet.

High fat diets, and inflammation are risk factors for colon cancer, however the underlying mechanisms remain to be fully elucidated. The transcriptional co-repressor HDAC3 has recently emerged as a key regulator of intestinal epithelial responses to diet and inflammation with intestinal-specific Hdac3 deletion (Hdac3IKO) in mice increasing lipid oxidation genes and the rate of lipid oxidation in enterocytes. Hdac3IKO mice are also predisposed to experimentally induced colitis, however whether this is driven by the intestinal metabolic reprogramming, and whether this predisposes these mice to intestinal tumourigenesis is unknown. Herein, we examined the effects of intestinal-specific Hdac3 deletion on colitis-associated intestinal tumourigenesis in mice fed a standard (STD) or HF diet (HFD). Hdac3IKO mice were highly prone to experimentally induced colitis, which was further enhanced by a HFD. Hdac3deletion also accelerated intestinal tumour development, specifically when fed a HFD and most notably in the small intestine where lipid absorption is maximal. Expression of proteins involved in fatty acid metabolism and oxidation (SCD1, EHHADH) were elevated in the small intestine of Hdac3IKO mice fed a HFD, and these mice displayed increased levels of lipid peroxidation, DNA damage, and apoptosis in their villi, as well as extensive expansion of the stem cell and progenitor cell compartment. These findings reveal a novel role for Hdac3 in suppressing colitis and intestinal tumorigenesis, particularly in the context of consumption of a HFD, and reveal a potential mechanism by which HFDs may increase intestinal tumorigenesis by increasing lipid oxidation, DNA damage and intestinal epithelial cell turnover.

Glutamine boosts intestinal stem cell-mediated small intestinal epithelial development during early weaning: Involvement of WNT signaling.

Early weaning usually causes small intestine epithelial development abnormality, increasing the risk of gastrointestinal diseases. Glutamine (Gln), enriching in plasma and milk, is widely reported to benefit intestinal health. However, whether Gln affects intestinal stem cell (ISC) activity in response to early weaning is unclear. Here, both the early weaning mice and intestinal organoids were used to study the role of Gln in regulating ISC activities. Results showed that Gln ameliorated early weaning-induced epithelial atrophy and augmented the ISC-mediated epithelial regeneration. Gln deprivation disabled ISC-mediated epithelial regeneration and crypt fission invitro. Mechanistically, Gln augmented WNT signaling in a dose-dependent manner to regulate ISC activity, while WNT signaling blockage abolished the effects of Gln on ISCs. Together, Gln accelerates stem cell-mediated intestinal epithelial development associated with the augmentation of WNT signaling, which provides novel insights into the mechanism by which Gln promotes intestinal health.

Maternal acrylamide exposure changes intestinal epithelium, immunolocalization of leptin and ghrelin and their receptors, and gut barrier in weaned offspring

Acrylamide (ACR) is an amide formed as a byproduct in many heat-processed starchy-rich foods. In utero ACR exposure has been associated with restricted fetal growth, but its effects of postnatal functional development of small intestine is completely unknown. The current study investigated the time- and segment-dependent effects of prenatal ACR exposure on morphological and functional development of small intestine in weaned rat offspring. Four groups of pregnant female Wistar rats were exposed to ACR (3 mg/kg b.w./day) for 0, 5, 10 and 15 days during pregnancy. Basal intestinal morphology, immunolocalization of gut hormones responsible for food intake and proteins of intestinal barrier, activity of the intestinal brush border disaccharidases, apoptosis and proliferation in intestinal mucosa were analyzed in offspring at weaning (postnatal day 21). The results showed that in utero ACR exposure disturbs offspring gut structural and functional postnatal development in a time- and segment-depended manner and even a short prenatal exposure to ACR resulted in changes in intestinal morphology, immunolocalization of leptin and ghrelin and their receptors, barrier function, activity of gut enzymes and upregulation of apoptosis and proliferation. In conclusion, prenatal ACR exposure disturbed the proper postnatal development of small intestine.

Colostrum insulin supplementation to neonatal Holstein bulls affects small intestinal histomorphology, mRNA expression, and enzymatic activity with minor influences on peripheral metabolism

The objectives of this study were to evaluate how varying colostral insulin concentrations influenced small intestinal development and peripheral metabolism in neonatal Holstein bulls. Insulin was supplemented to approximately 5× (70.0 μg/L; n = 16) or 10× (149.7 μg/L; n = 16) the basal colostrum insulin (12.9 μg/L; BI, n = 16) concentration to maintain equivalent macronutrient intake (crude fat: 4.1 ± 0.06%; crude protein: 11.7 ± 0.05%; and lactose: 1.9 ± 0.01%) among treatments. Colostrum was fed at 2, 14, and 26 h postnatal and blood metabolites and insulin concentration were measured at 0, 30, 60, 90, 120, 180, 240, 360, 480, and 600 min postprandial respective to the first and second colostrum meal. At 30 h postnatal, a subset of calves (n = 8/treatment) were killed to excise the gastrointestinal and visceral tissues. Gastrointestinal and visceral gross morphology and dry matter and small intestinal histomorphology, gene expression, and carbohydrase activity were assessed. Insulin supplementation tended to linearly reduce the glucose clearance rate following the first meal, whereas after the second meal, supplementation linearly increased the rate of glucose absorption and nonesterified fatty acid clearance rate, decreased the time to maximum glucose concentrations, and decreased the time to reach minimum nonesterified fatty acid concentrations. Additionally, insulin clearance rate was linearly increased by insulin supplementation following the second colostrum feeding. However, there were no overall differences between treatments in the concentrations of glucose, nonesterified fatty acids, or insulin in plasma or serum. With respect to macroscopic intestinal development, dry rumen tissue mass linearly decreased when insulin was supplemented in colostrum, and supplementation linearly increased duodenal dry tissue density (g dry matter/cm) while tending to increase duodenal dry tissue weight. Increasing the colostrum insulin concentration improved small intestinal histomorphological development in the distal small intestine, as ileal villi height and mucosal-serosal surface area index were increased by supplementing insulin. Lactase enzymatic activity linearly increased in the proximal jejunum while ileal isomaltase activity linearly decreased with insulin supplementation. These data indicate that changes in colostrum insulin concentrations rapidly affect gastrointestinal growth prioritization and carbohydrase activity. The changes in gastrointestinal ontology result in minor changes in postprandial metabolite availability and clearance.

Protective effects of resveratrol on permethrin-induced fetotoxicity in rats

Synthetic pyrethroid insecticides have been widely used for years to prevent harmful effects of insects and control disease vectors. In this study, the effects of resveratrol against the potential toxicity of permethrin, an effective pyrethroid derivative, on the fetus were investigated. Accordingly, Wistar female rats were divided into four groups as Control, Sham, Permethrin, and Permethrin + Resveratrol. Lung, liver, kidney and small intestine of developing fetuses were evaluated histopathologically. Also, Bone Morphogenetic Protein-4 (BMP-4) in bone tissue development and Fibroblast Growth Factor-1 (FGF-1) expressions in lung were examined immunohistochemically. All structures in the Control and Sham groups were normal. Permethrin caused epithelial damage, regression in bronchial and primitive alveolar development in the lung; congestion, edema and sinusoidal dilatation around the central vein in the liver; tubular epithelial degeneration, regression in glomeruli and tubule formation in the kidney; epithelial degeneration and irregularity in the villus structure in the small intestine. Immunohistochemical results indicated that permethrin administration decreased BMP-4 levels in bone tissue and FGF-1 levels in lung. Resveratrol application was found to greatly alleviate histopathological and immunohistopathological variability in all tissues. Oral consumption of permethrin by pregnant rats caused growth retardation and tissue damage in many different tissues in offspring. Intake of resveratrol during pregnancy showed protective effects against fetotoxicity caused by permethrin.

Malnutrition of pregnant beef cows and the impact on passive immunity transfer to calves

Nutritional management in rangeland beef cattle systems prioritises optimal body condition scores at calving for improved fertility and reproductive success. However, this focus often overlooks short-term dietary deficiencies before calving, which can lead to adverse outcomes for neonatal calves. This review explores the effects of beef cow malnutrition during the periparturient period on colostrum production, lactation onset, and passive immunity transfer to calves. Additionally, it discusses the long-term impact of such malnutrition on the offspring. By understanding how nutritional interventions affect the transition from gestation to lactation, it becomes possible to enhance calf health and survival in arid tropical environments. Commonly occurring short-term dietary restrictions, particularly protein deficiencies, can disrupt the hormonal equilibrium, resulting in reduced colostrum volume and quality, hindering calf growth and increasing mortality risks. Furthermore, dietary restrictions during this period affect critical physiological processes such as mammary gland blood flow and fetal small-intestine development. The review explores how these constraints influence colostrum production and immunoglobulin absorption by neonatal calves. Additionally, it highlights the significance of addressing other common nutrient deficiencies such as phosphorus and water and investigates the potential benefits of supplementing microbial products to enhance rumen function and protect cows from inflammation. Ultimately, addressing malnutrition during pregnancy is essential to prevent negative impacts on offspring performance, including alterations in carcass composition and muscle marbling. Consequently, cattle producers who aim for superior muscle marbling in the carcass by using costly genetics should give priority to enhancing nutritional programs for late-pregnant cows. In conclusion, a comprehensive understanding of the effects of malnutrition during the periparturient period on colostrum production, passive immunity transfer, and overall calf health is crucial for developing effective nutritional interventions that improve colostrum production, passive immunity transfer, and overall calf health in rangeland beef cattle systems.

Evaluating Ruminal and Small Intestinal Morphology and Microbiota Composition of Calves Fed a Macleaya cordata Extract Preparation.

The objective was to determine the impact of feeding MCE on ruminal and intestinal morphology and microbiota composition of calves. A total of 10 male and 10 female crossbred (dairy × beef) calves (6 d of age) were assigned randomly to control (CTL; n = 10) or MCE-supplemented (TRT; n = 10) groups. The MCE was fed in the milk replacer and top-dressed on the calf starter during pre-weaning (6 to 49 d) and post-weaning (50 to 95 d) periods, respectively. Calves were slaughtered at 95 d to collect rumen and intestinal samples to determine volatile fatty acid (VFA) profile, mucosal morphology, and microbiota composition. The effects of MCE were analyzed by accounting for the sex and breed effects. Feeding MCE increased rumen papillae length (p = 0.010) and intestinal villus height: crypt depth (p < 0.030) compared to CTL but did not affect rumen VFA profile. The TRT had a negligible impact on microbial community composition in both the rumen and the jejunum. In conclusion, feeding MCE from birth through weaning can improve ruminal and small intestinal mucosa development of calves despite the negligible microbiota composition changes observed post-weaning.

Modified Sijunzi granule decreases post-weaning diarrhea in Rex rabbits via promoting intestinal development.

Traditional Chinese medicine (TCM) formulas can be adjusted on the basis of TCM basic theory to achieve the best curative effect, especially for diseases with complex pathogenesis, such as post-weaning diarrhea (PWD). Shugan Jianwei Sijunzi decoction (SJ-SJZD) can be recognized as modified Sijunzi Decoction (SJZD) supplemented with Astragalus mongholicus Bunge, Bupleurum chinense DC, Citrus × aurantium L., and Crataegus pinnatifida Bunge (fruit) in a fixed dosage ratio. The inactive ingredients were subsequently added to make granule, which was Shugan Jianwei Sijunzi granule (SJ-SJZG). Previous studies have confirmed the antagonism of SJ-SJZG to PWD. However, the mechanism of SJ-SJZG protective effects on small intestine in weaned Rex rabbits remained unclear. Animals were randomly divided into negative control (NC), low dose (LD), medium dose (MD), high dose (HD), and positive control (PC). SJ-SJZG significantly increased the intestinal length and the jejunum villi length. The SIgA level was statistically increased in duodenum and jejunum with the ELISA. Immunohistochemical detection showed that SIgA protein expression was also increased significantly in jejunum. Meanwhile, the relative expression of Zo1 in duodenum and jejunum of SJ-SJZG group increased significantly. SJ-SJZG significantly increased the relative expression of occludin in duodenum and jejunum as well. Moreover, real-time PCR results showed a significant increase in GLUT2 and SGLT1 relative expression in ileum. SJ-SJZG could also obviously enhance the expression of GLUT2 in jejunum and the expression of SGLT1 in duodenum. In conclusion, SJ-SJZG had been proven to be effective in promoting the development of small intestine and improving the immunity of small intestine. Moreover, SJ-SJZG could ensure the integrity of mucosal barrier and increase the ability of intestine to absorb glucose in small intestine.

Development of small intestine and sugar absorptive capacity in goslings during pre- and post-hatching periods

This study was conducted to investigate the development patterns of small intestine, intestinal morphology, disaccharidase activities, and sugar transporter gene expression in goslings during pre- and post-hatching periods. Small intestine was sampled on embryonic d 23 and 27, day of hatch, and d 1, 4, and 7 post-hatching. A total of 18 eggs with the breed of Jilin White geese were selected at each sampling timepoint for measuring relevant parameters. Three eggs were considered as a group, with 6 groups in each sampling timepoint. Rapid development of small intestine was observed around the hatching, of which jejunum and ileum had relatively higher development rates. Villus surface area from three intestinal segments started to increase on embryonic d 27, and kept relatively stable during day of hatch to d 1 post-hatching, and following increased till d 7 post-hatching. A high priority of villi enrichment was observed in duodenum and jejunum. The activity of disaccharidase increased before hatching and kept relatively high-level post-hatching, of which the activity of disaccharidase was highest in jejunum. The expression of sugar transporter gene increased prior to hatching and then decreased post-hatching, of which jejunum and duodenum were sites with high sugar transporter gene expression. Rapid development in intestinal morphology, disaccharidase activities, and sugar transporter gene expression around the hatching indicated that goslings have high potential to digest and/or assimilate carbohydrates during its early-life, which provided a preparation for further digestion of exogenous feed. This study provided a profile of development patterns for intestinal morphology, disaccharidase activities, and sugar transporter gene expression in goslings, which was beneficial to understanding the characteristics of nutrient absorption during the early-life of goslings.

Intestinal Apc-inactivation induces HSP25 dependency.

The majority of colorectal cancers (CRCs) present with early mutations in tumor suppressor gene APC. APC mutations result in oncogenic activation of the Wnt pathway, which is associated with hyperproliferation, cytoskeletal remodeling, and a global increase in mRNA translation. To compensate for the increased biosynthetic demand, cancer cells critically depend on protein chaperones to maintain proteostasis, although their function in CRC remains largely unexplored. In order to investigate the role of molecular chaperones in driving CRC initiation, we captured the transcriptomic profiles of murine wild type and Apc-mutant organoids during active transformation. We discovered a strong transcriptional upregulation of Hspb1, which encodes small heat shock protein 25 (HSP25). We reveal an indispensable role for HSP25 in facilitating Apc-driven transformation, using both invitro organoid cultures and mouse models, and demonstrate that chemical inhibition of HSP25 using brivudine reduces the development of premalignant adenomas. These findings uncover a hitherto unknown vulnerability in intestinal transformation that could be exploited for the development of chemopreventive strategies in high-risk individuals.

Regulatory role of phosphoproteins in the development of bovine small intestine during early life.

The small intestine is the primary site of nutrient digestion and absorption, which plays a key role in the survival of neonatal calves. A comprehensive assessment of the phosphoproteomic changes in the small intestine of neonatal calves is unavailable; therefore, we used phosphopeptide enrichment coupled with liquid chromatography-tandem mass spectrometry to investigate the changes in the phosphoproteome profile in the bovine small intestine during the first 36 h of life. Twelve neonatal male calves were assigned to one of the following groups: (1) calves not fed colostrum and slaughtered approximately 2 h postpartum (n = 3), (2) calves fed colostrum at 1 to 2 h and slaughtered 8 h postpartum (n = 3), (3) calves fed 2 colostrum meals (at 1-2 and 10-12 h) and slaughtered 24 h postpartum (n = 3), (4) calves fed 3 colostrum meals (at 1-2, 10-12, and 22-24 h) and slaughtered 36 h postpartum (n = 3). Mid-duodenal, jejunal, and ileal samples of the calves were collected after slaughter. We identified 1,678 phosphoproteins with approximately 3,080 phosphosites, which were mainly Ser (89.9%), Thr (9.8%), and Tyr (0.3%) residues; they belonged to the prodirected (52.9%), basic (20.4%), acidic (16.6%), and Tyr-directed (1.7%) motif categories. The regional differentially expressed phosphoproteins included zonula occludens 2, sorting nexin 12, and protein kinase C, which are mainly associated with developmental processes, intracellular transport, vesicle-mediated transport, and immune system process. They are enriched in the endocytosis, tight junction, insulin signaling, and focal adhesion pathways. The temporal differentially expressed phosphoproteins included occludin, epsin 1, and bridging integrator 1, which were mainly associated with macromolecule metabolic process, cell adhesion, and growth. They were enriched in the spliceosomes, adherens junctions, and tight junctions. The observed changes in the phosphoproteins in the tissues of small intestine suggest the protein phosphorylation plays an important role in nutrient transport and immune response of calves during early life, which needs to be confirmed in a larger study.

Long-term chemically protected sodium butyrate supplementation in broilers as an antibiotic alternative to dynamically modulate gut microbiota

Chemically protected sodium butyrate (CSB) is a new kind of sodium butyrate. Our previous study found that 1,000 mg/kg of CSB had the potential capacity of improving growth performance and promoting early development of small intestine in broilers. This study aimed to investigate the effect of long-term antibiotics or CSB supplementation for intestinal microflora dynamical regulation in broilers. One hundred ninety-two 1-day-old Arbor Acres male broilers were randomly allocated into 3 dietary treatment (8 replicates per treatment) and fed with a basal diet (CON), a diet supplemented with the antibiotics (enramycin, 8 mg/kg and aureomycin, 100 mg/kg) (ANT), or a diet supplemented with 1,000 mg/kg of CSB, respectively. Results showed that dietary supplementation of CSB or ANT treatment elevated the weight gain and feed conversion ratio (FCR; P < 0.05), as compared with control (CON) group. Additionally, CON, CSB, or ANT administration dynamically altered the gut microbiota composition as time goes on. The increased presence of potential pathogens, such as Romboutsia and Shuttleworthia, and decreased beneficial bacteria such as Alistipes, Akkermansia, and Bacteroides were verified in new gut homeostasis reshaped by long-term antibiotics treatment, which has adverse effects on intestinal development and health of broilers. Conversely, CSB supplementation could dynamically enhance the relative abundance of Bacteroides, and decrease Romboutsia and Shuttleworthia in new microflora, which has positive effects on intestinal bacteria of broilers compared with CON group. Meanwhile, CSB supplementation was significantly increased the concentration of propionic acid and total short chain fatty acids (total SCFA; P < 0.05) in comparison with CON and ANT groups. Moreover, CSB treatment significantly increased anti-inflammatory and antioxidative capacities (P < 0.05) of broilers compared with ANT group. Taken together, we revealed characteristic structural changes of gut microbiota throughout long-term CSB or ANT supplementation in broilers, which provided a basic data for evaluating the mechanism of action affecting intestinal health by CSB or ANT administration and CSB as an alternative to antibiotics in the broilers industry.

Effects of in ovo feeding of methionine and/or disaccharide on post-hatching breast development, glycogen reserves, nutrients absorption parameters, and jejunum antioxidant indices in geese.

We investigated the effects of in ovo injection of methionine (Met) and/or disaccharide (DS) on breast muscle and small intestine development, and the aspect of the glycogen contents, digestive enzymes activities, and jejunal antioxidant parameters in geese after incubation. A total of 600 fertilized eggs were used in this study to be employed in a 2 × 2 factorial experiment. Eggs were randomly assigned to 4 groups, 6 replicates per group, and 25 eggs per replicate. Factors in four groups included non-injection, Met injection (5 g/L Met dissolved in 7.5 g/L NaCl), DS injection (25 g/L maltose and 25 g/L sucrose dissolved in 7.5 g/L NaCl), and DS plus Met injection (25 g/L maltose, 25 g/L sucrose, and 5 g/L Met dissolved in 7.5 g/L NaCl). As a result, birth weight, relative weight of breast muscle, diameter of myofiber, glycogen contents, jejunal villus and surface area, and jejunal digestive enzymes activities improved, while liver glucose-6-phosphatase activity decreased, by DS injection. Additionally, DS administration upregulated the expression of myogenic factor-5 (Myf-5) from breast muscle and sodium/glucose cotransporter protein-1 (SGLT-1) from jejunum. In ovo delivery of DS has long-term effects on the improvement of jejunal glucose transporter-2 (GLUT-2) and sucrase-isomaltase expression. In ovo feeding of Met improved the relative weight of breast muscle and small intestine, diameter of myofiber, length of small intestine, jejunal villus width, jejunal sucrase, Na+/K+ATPase and alkaline phosphatase activities, and jejunal glutathione (GSH) concentration, and decreased the jejunal glutathione disulfide (GSSH) and the ratio of GSSG to GSH, in early-life post-hatching. The breast muscle Myf-5 and myostatin expression, jejunal villus height and surface area, jejunal glutathione peroxidase concentration, and the expression of GLUT-2 in jejunum long-term improved by in ovo delivery of Met. Moreover, in ovo feeding of DS plus Met mixture synergistically improved the diameter of myofiber, jejunal villus height and width, jejunal sucrase, and alkaline phosphatase activities in early-life post-hatching, but long-term upregulated the expression of jejunal GLUT-2. Therefore, we concluded that in ovo injection of Met plus DS is an effective way to improve the development of gosling during post-hatching stages.

Prevalence of Small Intestinal Bacterial Overgrowth Syndrome in Patients with Irritable Bowel Syndrome who Have Suffered COVID-19

Aim. To study the prevalence of the small intestinal bacterial overgrowth syndrome in patients with irritable bowel syndrome with diarrhea who have had COVID-19 infection.Materials and methods. 60 patients with irritable bowel syndrome with diarrhea were examined. In 30 patients, irritable bowel syndrome was diagnosed after COVID-19 infection (main group). The comparison group consisted of 30 patients with classical stress-induced irritable bowel syndrome. The small intestinal bacterial overgrowth syndrome was diagnosed using a hydrogen breath test with lactulose loading in all patients.Results. In main group the small intestinal bacterial overgrowth syndrome was diagnosed in 93.3 % patients, which was statistically significantly higher (p &lt; 0.01) relative to the comparison group — 60.0 % patientsConclusion. Irritable bowel syndrome in patients who have undergone COVID-19 occurs against the background of the small intestinal bacterial overgrowth syndrome development.