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Dietary supplementation with sodium gluconate improves the growth performance and intestinal function in weaned pigs challenged with a recombinant Escherichia coli strain

BMC Veterinary Research volume 18, Article number: 303 (2022) Cite this article

Abstract

Background

The purpose of this research is to determine the effects of sodium gluconate (SG) on the growth performance and intestinal function in weaned pigs challenged with a recombinant Escherichia coli strain expressing heat-stable type I toxin (STa).

Results

Pigs (n = 24, 21 days of age) were randomly allocated to three treatments: Control group (pigs were fed basal diet), STa group (pigs were fed basal diet and challenged with a recombinant E. coli strain expressing STa), and SG group (pigs were fed basal diet supplemented with 2500 mg/kg sodium gluconate and challenged with a recombinant E. coli strain expressing STa). The trial period lasted for 15 days. On days 12 and 13, pigs in the STa and SG groups were orally administered with the recombinant Escherichia coli strain, while those in the control group were orally administered with normal saline at the same volume. On day 15, blood, intestinal tissues and colonic contents were collected for further analysis. Results showed that dietary SG supplementation had a tendency to increase average daily gain, and reduced (P < 0.05) feed to gain ratio, plasma glucose concentration, and mean corpuscular hemoglobin concentration as compared with control group on days 0-10 of trial. Additionally, dietary SG supplementation attenuated(P < 0.05) the morphological abnormalities of small intestinal and the increase of the number of eosinophils in blood of pigs challenged with the recombinant Escherichia coli strain on day 15 of trial. Compared with control group, diarrhea rate and the number of eosinophils in blood and the concentrations of malondialdehyde in the jejunum were increased (P < 0.05). The height, width and surface area of the villi of the duodenum, the width and surface area of villi of jejunum and the height and width of villi of ileum were decreased (P < 0.05) in pigs challenged with the recombinant Escherichia coli strain in the STa group compared with those in control group on day 15 of trial. However, these adverse effects were ameliorated (P < 0.05) by SG supplementation in the SG group on day 15 of trial. Furthermore, dietary SG supplementation could reduce (P < 0.05) the total bacterial abundance in the colon, but SG did not restore the recombinant Escherichia coli-induced microbiota imbalance in colon.

Conclusions

In conclusion, dietary supplementation with SG could improve piglet growth performance and alleviate the recombinant Escherichia coli-induced intestinal injury, suggesting that SG may be a promising feed additive for swine.

Peer Review reports

Background

The intestine, as the first line of defense against infections, is an important immune organ in the host, which is always exposed to a large number of toxins and antigens [1]. The mucosal barrier is the host first line of defense against the external environment [2]. Since many pathogens invade the host through the intestinal mucosa, the damage of the intestinal mucosal barrier will cause inflammation and sepsis [3, 4]. Weaning stress can be easily triggered due to poor digestion and stress resistance in weanling pigs, which leads to significant changes in intestinal morphology including severe villus atrophy, accelerated crypt cell division, and significant reduction in villus ratio, severely affecting the normal function of pig intestine [5, 6]. The intestinal structural damage induced by weaning stress causes reduced appetite, digestive disorders, diarrhea, slow growth, low feed utilization, poor mental state and appearance performance, which elicits great losses to pig industry [1, 7,8,9].

Nutritional measures are extensively employed to reduce weaning stress except controlling environmental conditions [10, 11]. Although in-feed antibiotics, high zinc, and high copper can effectively prevent pig diarrhea, widespread concerns have arisen on the antibiotic resistance and environmental pollution problems [12, 13]. Therefore, safe and environmentally friendly feed additives, such as probiotics, prebiotics, glutamine, antibacterial peptides and acidifiers, are gradually being valued in porcine production [14,15,16,17]. So far, many new feed additives have been developed, which can effectively improve growth performance and reduce diarrhea by improving intestinal function and immunity in the pigs [18,19,20]. Although many valuable feed additives have been studied, in order to promote the healthy development of the pig industry, more effective feed additives need to be developed. Because there are various problems that plague the healthy growth of piglets. The development of feed additives for different problems of piglet healthy growth will be more conducive to the efficient development of the pig industry. Meanwhile, the research reports on the effects of different potential feed additives can be used as a reference for other researchers, which will help them study more potential effective feed additives. Therefore, the effects of more potential feed additives on the growth performance of piglets need to be continuously studied. Sodium gluconate (SG) is different from the feed additives on the market including probiotics, amino acids and plant extracts, which is an organic compound. As a potential feed additive, SG has stable properties and is easy to industrialize. However, there is limited research on SG as a potential feed additive. Therefore, it is meaningful to study SG as a feed additive on the performance of piglets.

SG is also called gluconic acid, sodium salt, the chemical formula for which is C6H11NaO7 (Molecular weight: 218.14). SG is a beige solid organic compound that is chemically stable at room temperature. SG can effectively prevent hyponatremia syndrome, regulate the acid-base balance of the body and restore normal nerve activity. SG, as a new food additive that has attracted much attention, which has the advantages of abundant raw materials, better stability and so on [21]. The supplementation of SG in feed is safe and stable, and SG is easily absorbed in the intestine. In addition, SG can improve feed quality by preventing protein degradation and masking undesirable bitterness and astringency [22,23,24]. Previous studies have shown that dietary SG supplementation (2% SG contained in the diets, w/w) could improve the growth performance, the utilization of phytate phosphorus and the tibia ash content in chicks [25]. Moreover, SG (0.5% SG contained in the diets, w/w) could improve fecal odor index, hydrogen sulfide and ammonia production, enhance the growth of animals and prevent the Escherichia coli (E. coli) infection [26]. However, studies on dietary supplementation of SG to improve the growth performance of animals infected with pathogens are still very limited. Because the invasion of pathogens into intestinal epithelium is complex and the heat-stable type I (STa), one of enterotoxins produced by enterotoxigenic Escherichia coli, can impair intestinal function, our lab has established a pig diarrhea model induced by a recombinant E. coli strain expressing STa (LMG194-STa strain) to study the ability of feed additives to resist pathogenic infection in piglet intestine [27]. Therefore, the effects of dietary SG supplementation on the growth performance and intestinal function in pigs challenged by recombinant STa-expressing E. coli will be studied in this study.

Results

Growth performance

During days 0-10 of the trial, dietary supplementation with SG had a tendency to increase the average daily gain (ADG) (Fig. 1A). Dietary supplementation with SG did not affect the average daily feed intake (ADFI) (Fig. 1B). Dietary supplementation with SG reduced (P < 0.05) the feed to gain (F/G) ratio (Fig. 1C). Dietary supplementation with SG did not affect the diarrhea rate (DR) (Fig. 1D). On day 15 of the trial, the recombinant E. coli challenge increased (P < 0.05) the DR (Fig. 1E) of pigs in STa group. Dietary supplementation with SG had a tendency to reducethe increase inDR of pigs challenged with recombinant E. coli in SG group (Fig. 1E).

Fig. 1
figure 1

Effects of SG on the growth performance of piglets. The ADG (A), ADFI (B), F/G (C) and DR (D) on days 0-10 (before infection); The DR (E) on days 13-14 (post infection). CP: Control group; STa: STa group; SG: SG + STa group. Values are means and SD, n = 8. a, b, Values within a column not sharing a common superscript letter indicate significant difference at P < 0.05

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Blood biochemical and hematological parameters

The biochemical and hematological parameters are presented in Fig. 2. On day 10 of the trial, the concentration of blood glucose (Fig. 2A) and the mean corpuscular hemoglobin concentration (MCHC) (Fig. 2B) were decreased (P < 0.05) by SG supplementation. On day 15 of the trial, the recombinant E. coli challenge did not affect blood biochemical parameters (Fig. 2C). However, the recombinant E. coli challenge reduced (P < 0.05) the number of white cells and neutrophils in the blood, while increasing (P < 0.05) the number of eosinophils (EOS) in the blood (Fig. 2D) of pigs. Dietary supplementation of SG could restore (P < 0.05) the number of eosinophils in pigs challenged with the recombinant E. coli to normal levels (Fig. 2D).

Fig. 2
figure 2

Effects of SG on blood biochemical and hematological parameters in pigs. The blood biochemical parameters (A) and hematological parameters (B) on day 10 (before infection); blood biochemical parameters (C) and hematological parameters (D) on day 15 (post infection). CP: Control group; STa: STa group; SG: SG + STa group. Values are mean and SD, n = 8. a, b, Values within a column not sharing a common superscript letter indicate significant difference at P < 0.05

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Effects of SG supplementation on intestinal morphology

As illustrated in Fig. 3, the recombinant E. coli challenge reduced (P < 0.05) the villus height of the duodenum and ileum, which could be mitigated (P < 0.05) by dietary supplementation of SG (Fig. 3A). The recombinant E. coli challenge decreased (P < 0.05) the villus width of the duodenum, jejunum and ileum, while dietary supplementation of SG could alleviate (P < 0.05) the reduction in the villus width of the jejunum and ileum in pigs challenged with the recombinant E. coli strain (Fig. 3B). The recombinant E. coli challenge increased (P < 0.05) the ileal crypt depth, but decreased (P < 0.05) the colonic crypt depth (Fig. 3C). However, dietary SG supplementation could inhibit (P < 0.05) the decrease in colonic crypt depth induced by the recombinant E. coli challenge (Fig. 3C). Additionally, recombinant E. coli challenge induced (P < 0.05) the reductions in the villus surface area of the duodenum and jejunum, which could be restored (P < 0.05) by dietary supplementation of SG (Fig. 3D).

Fig. 3
figure 3

Effects of SG supplementation on intestinal morphology of pigs. CP: Control group; STa: STa group; SG: SG + STa group. Values are mean and SD, n = 8. a, b, c, Values within a column not sharing a common superscript letter indicate significant difference at P < 0.05

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Effects of SG supplementation on intestinal redox status

As shown in Fig. 4, compared with the pigs of the control group, the recombinant E. coli-challenged pigs exhibited an increase (P < 0.05) in MDA concentration in the jejunum (Fig. 4A). Dietary supplementation of SG decreased (P < 0.05) the concentration of MDA in the jejunum in SG group (Fig. 4A). The recombinant E. coli-challenged or dietary supplementation of SG pigs did not exhibited difference in CAT activity in the jejunum and colon (Fig. 4B). Dietary supplementation of SG decreased (P < 0.05) the activity of MPO in the jejunum of pigs challenged with recombinant E. coli in SG group (Fig. 4C). The recombinant E. coli-challenged or dietary supplementation of SG pigs did not exhibited difference in T-SOD activity in the jejunum and colon (Fig. 4D).

Fig. 4
figure 4

Effects of SG on intestinal redox status in piglets. CP: Control group; STa: STa group; SG: SG + STa group. Values are mean and SD, n = 8. a, b, Values within a column not sharing a common superscript letter indicate significant difference at P < 0.05

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Abundance of intestinal bacteria

Compared with the control group, recombinant E. coli infection increased (P < 0.05) the number of E. coli, Enterobacteriaceae family, Enterococcus genus, Lactobacillus genus and Clostridium coccoides, but reduced (P < 0.05) the number of Bifidobacterium genus in the colon of pigs. Dietary SG supplementation did not restore the changes in the number of E. coli, Enterobacteriaceae family, Enterococcus genus, Lactobacillus genus, Clostridium coccoides and Bifidobacterium genus caused by recombinant E. coli challenge. However, dietary SG supplementation reduced (P < 0.05) the number of the total bacterial abundance in the colon of pigs in SG group (Fig. 5).

Fig. 5
figure 5

Effects of dietary SG supplementation on colon bacteria of pigs after recombinant E. coli challenge. CP: Control group; STa: STa group; SG: SG + STa group. Values are mean and SD, n = 8. a, b, c, Values within a column not sharing a common superscript letter indicate significant difference at P < 0.05

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Discussion

In order to cope with the impaired growth, diarrhea and other diseases in weaning pigs, antibiotics are widely used as feed additives [28, 29]. However, long-term use of antibiotics in feed leads to antibiotic resistance, which disrupts the microecological balance in the intestines, induces secondary infections, and makes the treatment of bacterial infections more difficult. So far, antibiotic resistance has received widespread public concern [30, 31]. Antibiotics in feed are considered a risk factor for animal food safety in the world [32, 33]. China, the European Union, South Korea, the United States and other countries ban the addition of preventive antibiotics to feed [34]. To address the problem of antibiotic resistance, many potential antibiotic alternatives have been studied. These alternatives focus on reducing piglet diarrhea, lowering the crude protein and increasing the crude fiber in the piglet’s diet [35, 36]. In recent years, a variety of additives that may replace antibiotics have been extensively studied, including prebiotics, plant extracts, acidifiers, etc. [37]. In this study, we found that dietary SG supplementation had a tendency to increase the ADG (Fig. 1A) of pigs during days 0-10 of the trial. This result was consistent with that of Kang et al. (2014), who reported that dietary supplementation with 0.5% proline had a tendency to increase ADG [38]. Previous study has reported that Enterococcus faecium R1 can improve piglet growth performance by significantly reducing DR and F/G [18]. In agreement with previous research results [18], our findings exhibited that dietary SG supplementation reduced (P < 0.05) the F/G (Fig. 1C) during days 0-10 of the trial. Although dietary SG supplementation had no effect on the DR (Fig. 1D) of pigs before infection, it had a tendency to reduce the increase in DR (Fig. 1E) in pigs challenged with recombinant E. coli. These results suggested that dietary SG supplementation could improve the growth performance of piglets by increasing ADG and reducing F/G and exert beneficial effect in combating diarrhea in piglets caused by E. coli infection. Moreover, SG may have similar functions with Enterococcus faecium R1 and proline in improving the growth performance of piglets.

Although dietary SG supplementation improved the growth performance of pigs including the increased ADG and reduced F/G, it is remained unclear whether dietary supplementation of SG could enhance the ability of pigs to resist pathogenic infections. So far, weaned pig diarrhea induced by pathogenic microorganisms has greatly restricted the healthy development of pig farming and causes tremendous economic losses to the pig industry every year [39]. As a major cause of piglet diarrhea, enterotoxigenic E. coli colonizes the small intestine and then expresses the heat-stable enterotoxin. Pig diarrhea caused by the heat-stable enterotoxin can last for 3-5 days. Pig infected with enterotoxigenic E. coli will have mild diarrhea in the early stage and severe diarrhea causing dehydration in the later stage. In order to develop eco-friendly feed additives against enterotoxigenic E. coli infection, suitable and reliable animal models of infection are required. In previous studies, naturally infected pigs were often used as a model to evaluate the effectiveness of potential eco-friendly feed additives [40,41,42,43]. In the latest research, a piglet diarrhea model induced by recombinant E. coli was established, which can be used for nutritional and mechanistic studies of intestinal dysfunction [27]. Therefore, in this study, a piglet diarrhea model induced by recombinant E. coli was used to determine the ability of the dietary SG supplementation to resist enterotoxigenic E. coli infection in pigs.

Early weaning of pigs will cause changes in blood indicators, which can reflect the status of health, the level of metabolism, and cell permeability [44]. It is worth noting that dietary SG supplementation can reduce (P < 0.05) blood glucose (Fig. 2A) and MCHC (Fig. 2B) levels of pigs, but their values are still within the normal range. White blood cells play an important role in the host resistance to pathogen invasion, which are regarded as the important defense lines of the host defense system. When the host is infected by pathogens, the number and proportion of white blood cells will be changed [45]. Eosinophils quickly swallow pathogens that invade the host, such as bacteria and parasites. Neutrophils play a crucial part in the host innate immune system, which can engulf and kill pathogens [46]. In this study, the number of eosinophils was increased (P < 0.05), but the number of white blood cells and neutrophils was reduced (P < 0.05) in the STa group (Fig. 2D). Contrary to the previous research that dietary Lactobacillus rhamnosus LB1 supplementation significantly increased the number of eosinophils (P < 0.05) in pigs challenged with E. coli [47]. Our result showed that dietary SG supplementation attenuating the increase of the number of eosinophils (P < 0.05) in pigs challenged with recombinant E. coli (Fig. 2D). These results suggested that recombinant E. coli infection could cause immunological stress and dietary supplementation of SG could alleviate the host immunological stress.

The small intestine is the most important nutrient absorption organ in the animal body. Early weaning leads to mucosal atrophy, villus shortening, and crypt deepening in the small intestine [1, 48]. The surface area and width of villi reflect the ability of the small intestine to absorb nutrients. Some studies showed that the digestion and absorption of nutrients was closely related to the morphology of intestinal villi [49]. Under normal physiological conditions, the small intestine can effectively absorb nutrients. When E. coli infection impaired the mucosal morphology, the small intestinal dysfunction occurred [50]. Previous study reported that dietary N-Acetylcysteine supplementation improved the decrease of villus height in piglets challenged with porcine epidemic diarrhea virus [6]. In this study, these results showed that dietary SG supplementation not only exhibited an increase (P < 0.05) in the villus height of the duodenum and ileum (Fig. 3A), but also exhibited the elevation (P < 0.05) in the villus width of the duodenum, jejunum and ileum (Fig. 3B) and the increase (P < 0.05) in the villus surface area of the duodenum and jejunum in piglets challenged with recombinant E. coli. (Fig. 3D). These results suggested that dietary SG supplementation exhibited better effectsin repairing small intestinal injury caused by pathogenic microorganisms.. It is also suggested that dietary SG supplementation can reduce the increase of diarrhea in piglets challenged with recombinant E. coli by improving the small intestinal morphology.

As an active protease, SOD is a scavenger of oxygen free radicals in the body, which can prevent lipid peroxidation from damaging the structure and function of cell membranes. It is an important antioxidant enzyme in the organism, which can remove various metabolic wastes in tissues and cells, and maintain the antioxidant capacity of the host [51]. MDA is the final metabolite of lipid peroxidation in the body through ROS chain reaction. The degree of membrane oxidation can be determined based on the content of MDA, thereby assessing the degree of damage to the cell membrane [52]. CAT, an anti-oxidative enzyme, can catalyze the reduction of H2O2 to water [51,52,53]. Myeloperoxidase (MPO), as a rich granule enzyme, is a heme-containing peroxidase expressed mainly in neutrophils, which can catalyze the production of potent ROS [53]. MPO activity is related to the normal function and activation of neutrophils. Elevated levels of MPO are also associated with pathology such as coronary artery disease and endemic arsenic poisoning. In agreement with previous research results that dietary N-Acetylcysteine supplementation significantly reduced the increase of the content of MDA and the activity of MPO in jejunum in piglets challenged with β-conglycinin [54]. Our results showed that dietary SG supplementation reduced (P < 0.05) the content of MDA (Fig. 4A) and the activity of MPO (Fig. 4C) in the jejunum of pig challenged with recombinant E. coli. These results suggested that dietary SG supplementation could protect pig jejunal mucosae from oxidative stress by decreasing the content of MDA and the activity of MPO.

Some intestinal microbes can improve the host immune function and enhance the ability to resist infection [55]. Once intestinal flora homeostasis is disrupted, a large number of pathogenic bacteria will proliferate and damage intestinal mucosal, causing diarrhea and even sepsis. The intestinal mucosa and epithelial cells constitute the first biological barrier, which regulates the balance of the inherent flora and resists pathogens [4]. Lactobacillus genus can regulate the immune function development of pigs and resist inflammation caused by foreign antigens [56]. Lactobacillus genus can also enhance the activity of macrophages, and increase the number of WBC and serum protein content to improve the host immunity [57]. Bifidobacterium genus is an anaerobic gram-positive bacteria, which will be decreased in the intestine with age and can effectively treat diarrhea. Bifidobacterium genus could activate the macrophages, which functions in the host innate immune response. Metabolites of Bifidobacterium genus, such as protein and hydrogen peroxide, can inhibit or even kill pathogenic bacteria [58]. Clostridium coccoides is an anaerobic gram-positive bacillus, which can cause enteritis. Although Enterococcus genus is considered to have a positive role in cheese technology, it is regarded as an unreliable bacteria. This study showed that the recombinant E. coli infection caused the elevation (P < 0.05) in the number of E. coli, Enterobacteriaceae family, Enterococcus genus, Lactobacillus genus and Clostridium coccoides in the colon of pigs (Fig. 5), leading to a significant imbalance of the colon flora. Dietary SG supplementation cannot change the flora imbalance caused by pathogenic microorganisms, which was in agreement with previous research results that dietary puerarin supplementation cannot change the flora imbalance in the colon caused by pathogenic microorganisms [32]. Dietary puerarin supplementation significantly reduced the total bacterial abundance in the colon [32]. In this study, dietary SG supplementation reduced (P < 0.05) the total bacterial abundance in the colon. (Fig. 5). These results showed that recombinant E. coli challenge significantly increased the abundance of the dominant flora including Escherichia coli, Enterobacteriaceae family, Enterococcus genus, Lactobacillus genus and Clostridium coccoides. The dietary SG supplementation cannot affect the increase of the abundance of the dominant flora. However, the dietary SG supplementation significantly reduced the total bacterial abundance in the colon. These results suggested that SG may lead to a decrease in the total bacterial abundance by reducing the abundance of non-dominant flora in the colon.

Conclusions

In conclusion, dietary SG supplementation could improve the growth performance of pigs and alleviated the recombinant E. coli-induced intestinal injury in pigs. This research provides an important implication for the application of SG in the pig industry.

Materials and methods

Animals and experimental design

The animal experiment was approved by the Animal Care and Use Committee at Wuhan Polytechnic University (No. WPU202011003). Twenty-four healthy female crossbred pigs (Duroc×Landrace×Yorkshire) with similar body weight (5.56 Kg) were weaned at 21 days of age. All pigs were housed individually in stainless steel metabolic cages (1.20 × 1.10 m2), maintained at an ambient temperature of 22-25 °C in an environmentally controlled room by air-conditioning and acclimatized for 3 days. In order to avoid diarrhea caused by overfeeding in weaned pigs, this study adopted the restrict feeding. Pigs were fed 5 times a day at 8:00, 12:00, 15:00, 18:00, and 21:00, respectively. The corn- and soybean meal-based diet was formulated to meet National Research Council (NRC, 2012)-recommended requirements for all nutrients (Table 1) [18]. All piglets were randomly divided into three treatment groups (8 pigs per group): (1) control group, (2) STa group, and (3) SG group, which were fed the basal diet during the 3-day adaptation period. At 24 days of the age, Pigs in the control group and the STa group were fed a basal diet, and those in the SG group were fed the basal diet supplemented with 2500 mg/kg SG (Sigma-Aldrich-S2054). During days 1-10 of the trial, the growth performance of pigs in each group was analyzed by recording the body weight, the feed intake and diarrhea. To determine average daily gain (ADG), average daily fed intake (ADFI) and feed/gain ratio (F/G), individual piglets were weighed on days 1 and 10 of the trial, daily fed intake was the actual daily feed intake of weaned piglets. ADG (Kg/day) = gain (Kg, 8 piglets per treatment group)/10. ADFI (Kg/day) = total feed intake (Kg, 8 piglets per treatment group)/10. F/G (%) = total feed intake (Kg)/ gain (Kg, 8 piglets per treatment group) × 100. To determine the diarrhea rate, individual piglets were examined for diarrhea four times per day. Diarrhea was quantified by the following equation for each pig. Diarrhea rate (DR) (%) = total diarrhea incidences/8 × 100. The recombinant STa-expressing E. coli strain was grown at 37 °C in Luria-Bertani (LB) medium. After 8 hours of cultivation, the recombinant E. coli (OD600 = 0.8) strains were collected by centrifuging the bacterial cultures at 5000 rpm for 10 min at room temperature. Subsequently, the bacterial cells were suspended in physiological saline (1.0 × 109 CFU/mL). On days 12 and 13 of the trial, pigs in the STa and the SG groups were orally administered with the recombinant STa-expressing E. coli strain (10 mL) twice a day. Pigs in the control group were orally administered with the same volume of saline. During days 12-15 of the trial, the effects of SG on the growth performance in pigs challenged with the recombinant E. coli strain were analyzed by recording the feed intake, diarrhea, the body weight and average daily fed intake. On day 15 of the trial, all pigs were killed and dissected under anesthesia with an intravenous injection of pentobarbital sodium (50 mg/kg BW) to obtain intestinal tissues and contents by the previously described with minor modifications [33]. First, the abdominal cavity of the slaughtered pig was immediately opened with a scalpel to expose the whole gastrointestinal tract. Subsequently, the intestine was separated from the mesentery by using surgical scissors and immediately the separated intestine was placed on a frozen stainless steel tray. Finally, the 5-cm and 10-cm intestinal segments were separately collected from the distal duodenum, mid-jejunum, mid-ileum, and mid-colon. For morphological measurements, the 5-cm intestinal segments were washed gently with ice-cold normal saline and then fixed with 4% paraformaldehyde. The contents were carefully flushed with ice-cold normal saline from the 10-cm segments opened longitudinally. Mucosa was scraped and collected by using a sterile glass microscope slide at 4 °C from the 10-cm segments opened longitudinally without contents. The intestinal mucosae and contents collected were rapidly frozen in liquid nitrogen and stored at − 80 °C until analysis.

Table 1 Ingredients and contents of energy and nutrients of the basal diet (air-dry basis)
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Blood sample collection

On days 10 and 15 of the trial, blood was collected from the anterior vena cava of each piglet by using 10 mL heparinized vacuum tubes. After standing at room temperature for 15 min, the blood samples were centrifuged at 3500 rpm for 15 min to separate plasma, which was further aliquoted in centrifuge tubes and stored at -80 °C until analysis. Plasma biochemical parameters (including alanine transaminase, ALT; aspartate transaminase, AST; total bilirubin, TBIL; total protein, TP; albuminuria, ALB; cholesterol, CHOL; triglyceride, TG; blood urea nitrogen, BUN; alkaline phosphatase, ALP; creatinine, Crea; glucose, GLU; chloride, CL; glutamyl transferase, GGT) were measured with corresponding kits using a Hi-tachi 7020 Automatic Biochemical Analyzer (Hitachi, Tokyo, Japan). Theses kits used for plasma biochemical parameters were purchased from Hitachi Hi Tech Co., Ltd. Before starting to measure samples, the relevant parameters of different plasma biochemical parameters have been input into the system according to the instructions. Automatic blood analyzer (ADVIA® 2120/2120i, Siemens Healthcare Diagnostics Inc.) was used to measure hematological parameters. The test tube containing the sample was gently shaken to fully mix the blood sample, and then placed the test tube under the sampling needle. Then, the instrument was started running and analysis results were collected.

Measurement of intestinal morphology

To measure intestinal morphology, the paraformaldehyde-fixed 5-cm segments of duodenum, jejunum, ileum, and colon was taken, respectively. 5-cm segment of duodenum was collected from the front of the distal 15-cm of the duodenum. 5-cm segments of jejunum, ileum and colon were collected from the front of the middle 15 cm of the jejunum, ileum and colon, respectively. Subsequently, the segments of duodenum, jejunum, ileum and colon were separately dehydrated and embedded in paraffin. The intestinal sections were cut and then stained with hematoxylin and eosin stain. Intestinal morphology was measured by using a light microscope (Leica, Solms, Germany) as previously described with minor modifications [15]. Crypt depth (the distance from the crypt mouth to the base), villus width (the distance of the widest villi) and height (the distance from the villus tip to the crypt mouth) were measured using a linear ocular micrometer with a computer-assisted morphometric system (Leica, Solms, Germany). Villi and crypts that were only vertically oriented were measured. The surface area of the villus is equal to the height of the villus multiplied by the width of the villus.

Determination of the redox status in the intestinal mucosae

In order to obtain the mucosa, the collected intestinal segment was cut longitudinally, exposing the inside of the intestine. Then the cut intestines were spread flat on ice, with the intestine inner side facing up, and a thin glass slide was use to scrape the mucosa from the inside of the intestine. The collected mucosa was wrapped in tin foil and then frozen in liquid nitrogen until use. After grinding the frozen intestinal mucosa samples, the samples were well mixed in a nine-fold volume of pre-cooled saline. The mixture was then centrifuged at 3500 rpm for 15 min at 4 °C, and the supernatant was collected and frozen at -80 °C. Total superoxide dismutase (T-SOD), catalase (CAT), myeloperoxidase (MPO) and malondialdehyde (MDA) in the intestinal mucosae were determined by using commercially available kits including Total Superoxide Dismutase (T-SOD) assay kit (Hydroxylamine method), Catalase (CAT) assay kit (Ultraviolet), Myeloperoxidase assay kit, and Malondialdehyde (MDA) assay kit (TBA method) (Nanjing Jiancheng Bioengineering Institute, Nanjing, China).

Determination of intestinal microflora in colon digesta

The colon was placed on ice, and then a segment of intestine containing digesta was taken. The digesta was taken out as described above, placed in a sterile tube, stirred evenly and then stored in liquid nitrogen for the determination of microorganisms in the colon. The determination method for the number of total eubacteria, E. coli, Enterobacteriaceae family, Enterococcus genus, Clostridium coccoides, Lactobacillus genus, and Bifidobacterium genus in colon chyme was described briefly as follows. First of all, the intestinal contents were evenly ground in liquid nitrogen, and then 180-220 mg of uniformly ground intestinal contents were weighed and placed in a 1.5 mL centrifuge tube. Subsequently, the microbial DNA in colon chyme was extracted by using QIAamp™Fast DNA Stool Mini Kit (Cat. No.51604) as described by Yi et al. [29]. Finally, the aforementioned microorganisms in the colon chyme were determined by quantitative RT-PCR (qRT-PCR). Microbial samples were normalized by using the average cycle threshold (Ct) of 16S rDNA [29, 30] as a reference. Results were analyzed by using the 2 −ΔΔCt method [29, 30]. Primer sequences used for qRT-PCR are listed in Table 2. Each biological sample was run in triplicate.

Table 2 Sequences of the primers [25, 26] used for quantitative RT-PCR analysis
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Statistical analysis

Data was analyzed by one-way analysis of variance, expressed as mean values ± SEM. All statistical analyses were performed by using SPSS (Version 17.0, SPSS Inc., Chicago, IL, USA). Each pig was the experimental unit. Differences among treatment means were determined by Duncan’s multiple comparison test. Additionally, differences in the means of blood biochemical and hematological parameters on day 10 of trial and the growth performance (ADG, F/G ratio and DR) was determined by the Student’s paired t test. Possibility values < 0.05 was considered statistically significant.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

References

  1. Pluske JR, Hampson DJ, Williams IH. Factors influencing the structure and function of the small intestine in the weaned pig: a review. Livest Prod Sci. 1997;51:215–36.

    Article  Google Scholar 

  2. Richter JM, Schanbacher BL, Huang H, Xue JJ, Bauer JA, Giannone PJ. Lipopolysaccharide binding protein enables intestinal epithelial restituti. J Pediatr Gastroenterol Nutr. 2012;54:639–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Ritchie JM, Rui HP, Zhou XH, Iida T, Kodoma T, Ito S, et al. Inflammation and disintegration of intestinal villi in an experimental model for Vibrio parahaemolyticus-induced diarrhea. PLoS Pathog. 2012;8:e1002593.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Snel J, Harmsen HJM, Wielen PWJJ, Williams BA, Blok MC, Vahl HA, et al. Dietary strategies to influence the gastro-intestinal microflora of young animals, and its potential to improve intestinal health. J Chem Phys. 2002;65:5083–92.

    Google Scholar 

  5. Argenzio RA, Liacos JA, Levy ML, Meuten DJ, Lecce JG, Powell DW. Villous atrophy, crypt hyperplasia, cellular infiltration, and impaired glucose-Na absorption in enteric cryptosporidiosis of pigs. Gastroenterology. 98(5):1129–40. https://doi.org/10.1016/0016-5085(90)90325-u.

  6. Wang L, Zhou J, Hou YQ, Yi D, Ding BY, Xie JQ, et al. N-acetylcysteine supplementation alleviates intestinal injury in piglets infected by porcine epidemic diarrhea virus. Amino Acids. 2017;49:1931–43.

    Article  CAS  PubMed  Google Scholar 

  7. Zheng L, Duarte ME, Sevarolli Loftus A, Kim SW. Intestinal health of pigs upon weaning: challenges and nutritional intervention. Front Vet Sci. 2021;8:628258.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Wei X, Tsai T, Howe S, Zhao J. Weaning induced gut dysfunction and nutritional interventions in nursery pigs: a partial review. Animals (Basel). 2021;11(5):1279.

    Article  Google Scholar 

  9. Moeser AJ, Pohl CS, Rajput M. Weaning stress and gastrointestinal barrier development: implications for lifelong gut health in pigs. Anim Nutr. 2017;3(4):313–21.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Ji FJ, Wang LX, Yang HS, Hu A, Yin YL. Review: the roles and functions of glutamine on intestinal health and performance of weaning pigs. Animal. 2019;13:2727–35.

    Article  CAS  PubMed  Google Scholar 

  11. Upadhaya SD, Laguna FB, Bertaud B, Kim IH. Multi-strain yeast fraction product supplementation can alleviate weaning stress and improve performance and health of piglets raised under low sanitary conditions. J Sci Food Agric. 2019;99:6076–83.

    Article  CAS  PubMed  Google Scholar 

  12. Köck R, Cuny C. Multidrug-resistant bacteria in animals and humans. Med Klin Intensivmed Notfmed. 2020;115:189–97.

    Article  PubMed  Google Scholar 

  13. Yun J, Olkkola S, Hänninen ML, Oliviero C, Heinonen M. The effects of amoxicillin treatment of newborn piglets on the prevalence of hernias and abscesses, growth and ampicillin resistance of intestinal coliform bacteria in weaned pigs. PLoS One. 2017;15(12):e0172150.

    Article  CAS  Google Scholar 

  14. Xuan ZN, Kim JD, Heo KN, Jung HJ, Lee JH, Han YK, et al. Study on the development of a probiotics complex for weaned pigs. Asian Australas J Animal Sci. 2001;14:1425–8.

    Article  CAS  Google Scholar 

  15. Singh VP, Sharma J, Babu S, Rizwanulla SA. Role of probiotics in health and disease: a review. J Pak Med Assoc. 2013;63:253–7.

    PubMed  Google Scholar 

  16. Hou Y, Wang L, Zhang W, Yang Z, Ding B, Zhu H, et al. Protective effects of N-acetylcysteine on intestinal functions of piglets challenged with lipopolysaccharide. Amino Acids. 2012;43:1233–42.

    Article  CAS  PubMed  Google Scholar 

  17. Bhandari SK, Xu B, Nyachoti CM, Giesting DW, Krause DO. Evaluation of alternatives to antibiotics using an Escherichia coli K88+ model of piglet diarrhea: effects on gut microbial ecology. J Anim Sci. 2008;86:836–47.

    Article  CAS  PubMed  Google Scholar 

  18. Zhang YY, Wu T, Chen ZQ, Meng YX, Zhu ZK, Wang Q, et al. Dietary supplementation with Enterococcus faecium R1 attenuates intestinal and liver injury in piglets challenged by lipopolysaccharide. Animals. 2021;11:1424.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Bon ML, Davies HE, Glynn C, Thompson C, Madden M, Wiseman J, et al. Influence of probiotics on gut health in the weaned pig. Livest Sci. 2010;133:179–81.

    Article  Google Scholar 

  20. Wang JQ, Yin FG, Zhu C, Yu H, Niven SJ, DeLange CFM, et al. Evaluation of probiotic bacteria or their effects on the growth performance and intestinal microbiota of newly-weaned pigs fed fermented high-moisture maize. Livest Sci. 2012;145:79–86.

    Article  Google Scholar 

  21. Wang M, Pan, Hongchun, Liu, & Hong, et al. Physicochemical properties, characterization, and antioxidant activity of sodium ferric gluconate complex. Food Sci Technol Res. 2016;22(5):639–46.

    Article  CAS  Google Scholar 

  22. Guo Y, Shi Y, Li F, Chen J, Zhao Z. Effects of sodium gluconate and phytase on performance and bone characteristics in broiler chickers. Anim Feed Sci Technol. 2009;150:270–82.

    Article  CAS  Google Scholar 

  23. Junqueira OM, Duarte KF, Garcia EA, Sgavioli S, Molino ADB. Effect of sodium gluconate on performance，carcass characteristics, and intestinal morphometry of broilers from 22 to 42 days of age. Acta Scientiarum Animal Sci. 2012;34:35–40.

    CAS  Google Scholar 

  24. Hiroyuki T, Ryouko K. Sodium gluconate and potassium gluconate as substitutes for sodium chloride in bread making. Food Sci Technol Res. 2002;8:75–9.

    Article  Google Scholar 

  25. Rafacz-Livingston KA, Parsons CM, Jungk RA. The effects of various organic acids on phytate phosphorus utilization in chicks. Poult Sci. 2005;84:1356.

    Article  CAS  PubMed  Google Scholar 

  26. Koyama H, Okada M, Okumura T, Mishiba T, Yamada K, Tsukahara T, et al. Effect of dietary sodium gluconate on growth, prevention of Escherichia coli infection and fecal malodor of piglets. J Animal Hygiene. 2003;29:113–22.

    Google Scholar 

  27. Wu T, Lv Y, Li XN, Zhao D, Yi D, Wang L, et al. Establishment of a recombinant Escherichia coli-induced piglet diarrhea model. Front Biosci (Landmark Ed). 2018;23:1517–34.

    Article  CAS  Google Scholar 

  28. Spreeuwenberg MA, Verdonk JM, Gaskins HR, Verstegen MW. Small intestine epithelial barrier function is compromised in pigs with low feed intake at weaning. J Nutr. 2001;131:1520–7.

    Article  CAS  PubMed  Google Scholar 

  29. Yi D, Li BC, Hou YQ, Wang L, Zhao D, Chen HB, et al. Dietary supplementation with an amino acid blend enhances intestinal function in piglets. Amino Acids. 2018;50:1089–100.

    Article  CAS  PubMed  Google Scholar 

  30. Wu MJ, Zhang Q, Yi D, Wu T, Chen HB, Guo SS, et al. Quantitative proteomic analysis reveals antiviral and anti-inflammatory effects of puerarin in piglets infected with porcine epidemic diarrhea virus. Front Immunol. 2020;11:169.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Davies J, Davies D. Origins and evolution of antibiotic resistance. Microbiol. Mol. Biol. Rev. 74(3):417–33. https://doi.org/10.1128/MMBR.00016-10.

  32. Wu MJ, Yi D, Zhang Q, Wu T, Yu K, Peng M, et al. Puerarin enhances intestinal function in piglets infected with porcine epidemic diarrhea virus. Sci Rep. 2021;11:6552.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Wang L, Hou Y, Yi D, Ding B, Zhao D, Wang Z, et al. Beneficial roles of dietary oleum cinnamomi in alleviating intestinal injury. Front. Biosci. (Landmark Ed.). 2015;20:814–28.

    Article  CAS  Google Scholar 

  34. Westendorp WF, Vermeij JD, Zock E, Hooijenga IJ, Kruyt ND, Bosboom HJL, et al. The preventive antibiotics in stroke study (PASS): a pragmatic randomised open-label masked endpoint clinical trial. Lancet. 2015;385:1519–26.

    Article  CAS  PubMed  Google Scholar 

  35. Kong XF, Wu GY, Liao YP, Hou ZP, Liu HJ, Yin FG, et al. Dietary supplementation with Chinese herbal ultra-fine powder enhances cellular and humoral immunity in early-weaned piglets. Livest Sci. 2007;108:94–8.

    Article  Google Scholar 

  36. Hao Y, Piao X, Piao X. Saikosaponin-d inhibits β-conglycinin induced activation of rat basophilic leukemia-2H3 cells. Int Immunopharmacol. 2012;13:257–63.

    Article  CAS  PubMed  Google Scholar 

  37. Windisch W, Schedle K, Plitzner C, Kroismayr A. Use of phytogenic products as feed additives for swine and poultry. J Anim Sci. 2008;86:14018.

    Article  Google Scholar 

  38. Kang P, Zhang L, Hou Y, Ding B, Yi D, Wang L, et al. Effects of L-proline on the growth performance, and blood parameters in weaned lipopolysaccharide (LPS)-challenged pigs. Asian-Australas J Anim Sci. 2014;27(8):1150–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Zhao ZP, Yang Z, Lin WD, Wang WY, Yang J, Jin WJ, et al. The rate of co-infection for piglet diarrhea viruses in China and the genetic characterization of porcine epidemic diarrhea virus and porcine kobuvirus. Acta Virol. 2016;60:55–61.

    Article  PubMed  Google Scholar 

  40. Makino S, Watarai M, Tabuchi H, Shirahata T, Furuoka H, Kobayashi Y, et al. Genetically modified Shiga toxin 2e (Stx2e) producing Escherichia coli is a vaccine candidate for porcine edema disease. Microb Pathog. 2001;31:1–8.

    Article  CAS  PubMed  Google Scholar 

  41. Macleod DL, Gyles CL, Wilcock BP. Reproduction of edema disease of swine with purified Shiga-like toxin-II variant. Vet Pathol. 1991;28:66–73.

    Article  CAS  PubMed  Google Scholar 

  42. Oanh TKN, Nguyen VK, Greve HD, Goddeeris BM. Protection of piglets against edema disease by maternal immunization with Stx2e toxoid. Infection & Immunity. 2012;80:469–73.

    Article  CAS  Google Scholar 

  43. Johansen M, Andresen LO, Jorsal SE, Thomsen LK, Waddell TE, Gyles CL. Prevention of edema disease in pigs by vaccination with verotoxin 2e toxoid. Revue Canadienne De Recherche Vétérinaire. 1997;61:280–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Wu T, Li K, Yi D, Wang L, Zhao D, Lv Y, et al. Dietary supplementation with trihexanoin enhances intestinal function of weaned piglets. Int J Mol Sci. 2018;19:3277.

    Article  PubMed Central  CAS  Google Scholar 

  45. Han J, Liu YL, Fan W, Chao J, Hou YQ, Yin YL, et al. Dietary L-arginine supplementation alleviates immunosuppression induced by cyclophosphamide in weaned pigs. Amino Acids. 2009;37:643–51.

    Article  CAS  PubMed  Google Scholar 

  46. Liu Y, Jing L, Shi J, Hou Y, Zhu H, Zhao S, et al. Increased expression of the peroxisome proliferator-activated receptor γ in the immune system of weaned pigs after Escherichia coli lipopolysaccharide challenge. Vet Immunol Immunopathol. 2008;124:82–92.

    Article  CAS  PubMed  Google Scholar 

  47. Wu T, Shi Y, Zhang Y, Zhang M, Zhang L, Ma Z, et al. Lactobacillus rhamnosus LB1 alleviates Enterotoxigenic Escherichia coli-induced adverse effects in piglets by improving host immune response and anti-oxidation stress and restoring intestinal integrity. Front Cell Infect Microbiol. 2021;11:724401.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Jin LZ, Marquardt RR, Zhao X. A strain of Enterococcus faecium (18C23) inhibits adhesion of enterotoxigenic Escherichia coli K88 to porcine small intestine mucus. Appl Environ Microbiol. 2000;66(10):4200–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Thomson ABR, Keelan M, Thiesen A, Clandinin MT, Ropeleski M, Wild GE. Small bowel review diseases of the small intestine. Digestive Dis Sci. 2001;46:2555–66.

    Article  CAS  Google Scholar 

  50. Pluske JR, Williams IH, Aherne FX. Maintenance of villous height and crypt depth in piglets by providing continuous nutrition after weaning. Anim Sci. 2010;62:131–44.

    Article  Google Scholar 

  51. Huth ME, Ricci AJ, Cheng AG. Mechanisms of aminoglycoside ototoxicity and targets of hair cell protection. Int J Otolaryngol. 2011;937861.

  52. Fang YZ, Yang S, Wu G. Free radicals, antioxidants, and nutrition. Nutrition. 2002;18:872–9.

    Article  CAS  PubMed  Google Scholar 

  53. Reumaux D, Boer M, Meijer AB, Duthilleul P, Roos D. Natural and disease associated anti-myeloperoxidase (MPO) autoantibodies. Autoimmun Rev. 2008;7:421–5.

    Article  CAS  Google Scholar 

  54. Wang H, Li C, Peng M, Wang L, Zhao D, Wu T, et al. N-Acetylcysteine improves intestinal function and attenuates intestinal autophagy in piglets challenged with β-conglycinin. Sci Rep. 2021;11(1):1261.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Mitsuoka T. Intestinal flora and human health. Asia Pac J Clin Nutr. 1996;5:2–9.

    CAS  PubMed  Google Scholar 

  56. Heeney DD, Gareau MG, Marco ML. Intestinal Lactobacillus in health and disease, a driver or just along for the ride? Curr Opin Biotechnol. 2018;49:140–7.

    Article  CAS  PubMed  Google Scholar 

  57. Suzuki K, Fagarasan S. How host-bacterial interactions lead to IgA synthesis in the gut. Trends Immunol. 2008;29(11):523–31.

    Article  CAS  PubMed  Google Scholar 

  58. Orrhage K, Nord CE. Bifidobacteria and lactobacilli in human health. Drugs Under Exp Clin Res. 2000;26(3):95–111.

    CAS  Google Scholar 

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Acknowledgments

We thank our students and technicians for their contributions to this research.

Funding

This work was jointly supported by the National Key R&D Program of China (grant number 2016YFD0501210), National Natural Science Foundation of China (32072762), Hubei Provincial Key R&D Program (2019ABA083), and the Program of National Agricultural Research Outstanding Talents of China (2015).

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Author notes

  1. Yanyan Zhang, Dan Yi and Haiwang Xu contributed equally to this work and should be considered co-first authors.

Authors and Affiliations

  1. Hubei Key Laboratory of Animal Nutrition and Feed Science; School of animal science and nutrition engineering, Wuhan Polytechnic University, Wuhan, 430023, China

    Yanyan Zhang, Dan Yi, Haiwang Xu, Zihan Tan, Yuxuan Meng, Tao Wu, Lei Wang, Di Zhao & Yongqing Hou

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  1. Yanyan Zhang
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Contributions

YZ, YD and YH planned the project and designed the experiments. HX conducted the experiments. ZT, YZ and YM carried out the data analysis. TW, LW and DZ contributed reagents preparation and samples collection. YZ, DY and YH wrote the manuscript. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Yongqing Hou.

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Ethics approval and consent to participate

This study was approved by the Animal Care and Use Committee at Wuhan Polytechnic University (Approval code: WPU202011003). All animal experiments were conducted following the guidelines of the Research Ethics Committee of the College of Animal Science and Nutritional Engineering, Wuhan Polytechnic University. The experiments were also carried out in accordance with relevant guidelines and regulations and the study was carried out in compliance with the ARRIVE guidelines (https:// arriv eguid elines.org/).

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Zhang, Y., Yi, D., Xu, H. et al. Dietary supplementation with sodium gluconate improves the growth performance and intestinal function in weaned pigs challenged with a recombinant Escherichia coli strain. BMC Vet Res 18, 303 (2022). https://doi.org/10.1186/s12917-022-03410-5

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Keywords

  • Weaned pig
  • Growth performance
  • Sodium gluconate
  • Recombinant Escherichia coli strain
  • Intestinal function

BMC Veterinary Research

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