A stage-by-stage combined feed additive for improving sow production performance and application thereof

Abstract

The present application relates to the technical field of biology, and particularly relates to a staged combined feed additive for improving the production performance of sows and application thereof. The present application can effectively relieve the perinatal stress of sows, reduce embryo death, reduce the incidence of IUGR piglets, improve the uniformity of the average birth weight of piglets in a litter, shorten the labor process, and improve the oxytocin and prolactin levels in sows, promote postpartum recovery, and enhance lactation function by combining three different strains in different gestation stages of sows. The present application significantly improves the production performance of sows by precise nutritional regulation in different stages.

Description

Technical Field

[0001] This invention relates to the field of biotechnology, and in particular to a staged combined feed additive for improving sow reproductive performance and its application. Background Technology

[0002] In recent years, with the rapid development of intensive pig farming, large-scale pig farms have been continuously reducing production costs while pursuing high output, and fully tapping the reproductive performance of sows has become a key link in reducing costs and increasing efficiency.

[0003] Currently, most feed additives are chemically synthesized drugs, including hormones and antibiotics. While these additives can improve sow productivity in the short term, their drawbacks cannot be ignored: antibiotics, while inhibiting harmful bacteria, can disrupt the intestinal microecological balance, thereby weakening digestive function; hormones may accumulate along the food chain, forming residues in animal-derived products and posing a potential threat to human health. Against this backdrop, microbial preparations, with their green and safe characteristics, are increasingly attracting widespread attention from the industry as an important alternative to chemical additives. Summary of the Invention

[0004] In view of this, the present invention proposes a staged combined feed additive for improving sow reproductive performance and its application.

[0005] The technical solution of this invention is implemented as follows:

[0006] In a first aspect, the present invention provides a staged combined feed additive for improving the reproductive performance of sows, the staged combined feed additive comprising a stage one feed additive and a stage two feed additive.

[0007] The Phase 1 feed additive includes Bacillus pumilus preparations and Streptococcus thermophilus preparations; the Phase 2 feed additive includes Bacillus amyloliquefaciens preparations.

[0008] Phase 1 refers to the period from day 1 to day 84 of pregnancy, and Phase 2 refers to the period from day 85 of pregnancy to delivery.

[0009] The preservation number of the Bacillus amyloliquefaciens is CCTCC NO: M2015359.

[0010] Furthermore, the viable count in the Bacillus pumilus preparation is ≥6.0 × 10⁻⁶. 9 CFU / g, the viable count in the thermophilic streptococcal preparation is ≥6.0×10⁻⁶. 9 CFU / g. Furthermore, the amount of the *Bacillus pumilus* preparation added to the feed is 150 mg / kg; the amount of the *Streptococcus thermophilus* preparation added to the feed is 150 mg / kg.

[0011] Furthermore, the viable count in the Bacillus amyloliquefaciens preparation is ≥6.0 × 10⁻⁶. 9 CFU / g. Furthermore, the dosage of the Bacillus amyloliquefaciens preparation added to the feed is 300 mg / kg.

[0012] Secondly, the present invention provides the application of the feed additive in the preparation of feed that improves the reproductive performance of sows. Further, the improvement of sow reproductive performance includes the following aspects:

[0013] (1) Improve the birth weight and uniformity of piglets;

[0014] (2) Reduce IUGR rate and stillbirth rate; IUGR rate is the incidence of intrauterine growth restriction (IUGR);

[0015] (3) Shorten labor and enhance lactation.

[0016] It should be noted that the present invention is a natural result of improving production performance through nutrition and feeding management methods, and is not intended to diagnose or treat any disease in sows.

[0017] Thirdly, the present invention provides a staged combined feed to improve the reproductive performance of sows, the staged combined feed including a stage one feed and a stage two feed.

[0018] The Phase 1 feed consists of the following components: 0.015% of the total feed weight of Bacillus pumilus preparation, 0.015% of the total feed weight of Streptococcus thermophilus preparation, and the remainder of corn-soybean meal diet.

[0019] The Phase 2 feed consists of the following components: 0.03% of the total feed weight of Bacillus amyloliquefaciens preparation, and the remainder of a corn-soybean meal diet;

[0020] Phase 1 refers to the period from day 1 to day 84 of pregnancy, and Phase 2 refers to the period from day 85 of pregnancy to delivery.

[0021] The preservation number of the Bacillus amyloliquefaciens is CCTCC NO: M2015359.

[0022] Fourthly, the present invention provides a method for feeding pregnant sows according to the said feed.

[0023] In the first stage, the animal was fed the first stage feed at a rate of 1.5 kg / head per day.

[0024] In Phase Two, the animal is fed Phase Two feed at a rate of 2.5 kg / head per day.

[0025] The feed additives involved in this invention are sourced from the following sources:

[0026] The *Bacillus amyloliquefaciens* of this invention was deposited on June 4, 2015, at the China Center for Type Culture Collection (CCTCC) at Wuhan University, Wuhan, Hubei Province, with accession number CCTCCNO: M2015359. This biological material has been published in Chinese Patent CN113229398A. It is available to the public from the CCTCC or purchased from Hubei Huada Ruier Technology Co., Ltd.

[0027] Streptococcus thermophilus and Bacillus pumilus are conventional commercially available preparations. In this invention, both Streptococcus thermophilus and Bacillus amyloliquefaciens were produced by Hubei Huada Ruier Technology Co., Ltd.

[0028] The beneficial effects of the present invention include at least the following:

[0029] This invention, through the combined application of three different bacterial strains at different stages of sow gestation, effectively alleviates peripartum physiological stress in sows, reduces embryonic mortality, thereby lowering the incidence of IUGR piglets, improving the uniformity of birth weight within litters, significantly shortening the duration of farrowing, increasing oxytocin and prolactin levels in sows, promoting postpartum recovery, and enhancing lactation. Furthermore, by employing differentiated feed additive combinations at different gestation stages, this invention achieves precise nutritional regulation, effectively improving the overall reproductive performance of sows. Detailed Implementation

[0030] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions of this invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of this invention, not all embodiments. Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this invention. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer shall be followed. Reagents or instruments whose manufacturers are not specified are all conventional products that can be purchased commercially.

[0031] Example

[0032] 1. Laboratory animals and group feeding

[0033] Eighty-eight healthy Landrace × Large White crossbred sows of the same parity were selected and randomly divided into 11 groups. The control group was fed a corn-soybean meal diet. This diet was prepared by Jingzhou Haida Feed Co., Ltd., and its formula is as follows:

[0034] Table 1: Composition and nutrient levels of the experimental diets

[0035]

[0036] Note:

[0037] 1) The premix provides VA 12000IU, VE 24IU, VK3 2.0mg, thiamine 2.0mg, riboflavin 6.0mg, pyridoxine 4.0mg, VB12 24μg, niacin 30mg, pantothenic acid 20mg, folic acid 3.6mg, and biotin 0.4mg per kilogram of feed.

[0038] 2) Dry matter, crude protein, crude fiber, calcium, and total phosphorus are measured values, while other nutrient levels are calculated values;

[0039] 3) The proportions and contents mentioned are all mass percentages (wt%).

[0040] Other groups received corresponding probiotic supplements in their basal diets using a restricted feeding method. In the first phase, the supplement was 1.5 kg / head / day, fed twice a day at 8:00 AM and 4:00 PM, with each feeding being 0.75 kg / head. In the second phase, the supplement was 2.5 kg / head / day, fed twice a day at 8:00 AM and 4:00 PM, with each feeding being 1.25 kg / head. During the experiment, all groups had free access to water, were managed according to routine immunization and deworming programs, and the health status of postpartum sows was observed.

[0041] Table 2 Feeding details for the experimental groups

[0042]

[0043] 2. Testing of sow reproductive performance

[0044] The specific performance indicators of sows in all experimental and control groups are as follows:

[0045] Total number of piglets born: The total number of piglets born to a sow at the time of farrowing.

[0046] Live piglets: Piglets that are born with independent breathing, heartbeat, or the ability to move.

[0047] Stillbirth count: The number of stillborn babies who had no vital signs (no breathing, heartbeat, or voluntary movement) at the time of delivery.

[0048] Stillbirth rate (%) = (number of stillbirths / total number of piglets born) × 100%.

[0049] Number of IUGR pigs per litter: Piglets with a birth weight < 1.1 kg are defined as IUGR (intrauterine growth restriction) pigs, and the number of IUGR pigs per litter is recorded.

[0050] IUGR pig birth rate (%) = (Number of IUGR pigs / Total number of piglets born) × 100%.

[0051] Immediately after birth, wipe the mucus off the bodies of all live piglets, weigh them at birth (kg), and calculate the average birth weight and litter weight (kg) of each litter (i.e., the sum of the birth weights of all live piglets in that litter).

[0052] Coefficient of variation (CV, %) = (Standard deviation of birth weight per litter / Average birth weight of piglets in the litter) × 100%. All data were recorded per litter, and each sow (i.e., each litter) was used as an experimental unit for subsequent statistical analysis.

[0053] The experimental results were initially processed using Excel 2010, followed by one-way ANOVA using SPSS 22.0 statistical software. If significant differences were found, Duncan's method was used for multiple comparisons. The experimental results are expressed as mean ± standard error.

[0054] The sow reproductive performance results are shown in Table 3:

[0055] Table 3 Results of sow reproductive performance

[0056]

[0057] Note: Different lowercase letters in the same column indicate significant differences (p < 0.05, Duncan multiple comparisons); the same letter indicates no significant difference (p > 0.05). Each treatment group has n=8. CV represents the degree of variation in birth weight among piglets within the same litter.

[0058] The results showed that experimental group 8 ranked first or second best among all treatment groups in key indicators such as number of live piglets, litter weight, birth weight, stillbirth rate, IUGR rate and uniformity of piglets. Moreover, the coefficient of variation of weight within the litter of piglets was the lowest, indicating that this treatment had the best overall effect in improving sow productivity and piglet uniformity.

[0059] The gestation period of sows can be divided into two physiological stages: Early gestation (days 1-84): This stage focuses on embryo implantation, placental development, and fetal organ differentiation. The mother needs to maintain an anti-inflammatory, stress-resistant, and stable uterine environment. Late gestation (days 85 to farrowing): During this stage, the fetus experiences exponential weight gain, mammary gland development and colostrum synthesis begin, and the demand for high feed digestibility, high nutrient absorption, and enhanced immunity increases significantly.

[0060] The feeding regimen for experimental group 8 provided in this application achieves targeted matching of the above two stages: In the early stage, 150 mg / kg of *Bacillus pumilus* and 150 mg / kg of *Streptococcus thermophilus* were added to the diet. *Bacillus pumilus* secretes antimicrobial lipopeptides, exerting an anti-inflammatory effect; *Streptococcus thermophilus* produces lactic acid, regulating intestinal pH. The two work synergistically to inhibit the colonization of harmful bacteria in the intestine, reducing the risk of intrauterine infection, thereby reducing embryonic death caused by infection and subsequent stillbirth and IUGR. A stable maternal intrauterine environment also helps reduce polarization in fetal weight, laying the foundation for subsequent uniform growth. In the later stage, 300 mg / kg of *Bacillus amyloliquefaciens* was added to the diet. This strain produces high levels of amylase, protease, and lipase, significantly improving the digestibility and absorption of feed nutrients to meet the nutritional needs of rapid fetal weight gain. The high dose maximizes its enzyme production potential, breaking down cellulose, starch, and protein into easily absorbed small molecules and directly supplying them to the fetus. Meanwhile, the bacitracin and other metabolites produced by Bacillus amyloliquefaciens can enhance the immunity of pregnant sows, reduce stress response, promote balanced nutrient absorption by all fetuses, and avoid litter weight differences caused by uneven distribution of maternal nutrition.

[0061] In experimental group 7, the lack of synergistic effect of single strains with Streptococcus thermophilus in the early stage resulted in insufficient anti-inflammatory effect; the later compounding may have led to metabolic competition between strains, resulting in lower absorption efficiency than the high-dose single-strain strategy of experimental group 8, and poorer uniformity. In experimental group 10, the long-term coexistence of the three strains may have caused metabolic antagonism, and the dosage added per feed was relatively low, resulting in weaker enzyme production capacity in the later stage compared to group 8. Therefore, litter weight, live birth rate, and uniformity were slightly inferior to group 8. In experimental groups 4-6, no high doses of amylolytic single strains were used in the later stage, and the absence or insufficient dosage of a certain strain in the early and late stages of the combination led to weaker nutrient absorption capacity in the later stage or weaker anti-inflammatory capacity in the early stage compared to group 8, with significantly poorer indicators.

[0062] 3. Detection of sow blood parameters and farrowing process

[0063] Blood parameters and labor progress were measured in all sows in the experimental and control groups. Timing was started immediately after the sow gave birth to the first piglet (start of labor), and blood was collected from the ear vein at the same time.

[0064] After collecting blood samples and allowing them to stand for 30 min, the samples were centrifuged at 3000 r / min for 15 min at 4℃ to separate the serum, which was then stored at -20℃ for later testing. The levels of oxytocin (purchased from Shanghai Kechengwei Biotechnology Co., Ltd., product code: KCW21239) and prolactin (purchased from Shanghai Kechengwei Biotechnology Co., Ltd., product code: KCW21590) in the serum were determined using an ELISA kit.

[0065] Stop timing when all piglets are born and the placenta is completely expelled; record this moment as the end of the labor process. Labor duration (min) = End of labor time - Start of labor time.

[0066] The blood parameters and farrowing results of the sows are shown in Table 4:

[0067] Table 4. Blood parameters and farrowing results of sows

[0068]

[0069] Note: Different lowercase letters in the same column indicate significant differences (p < 0.05, Duncan multiple comparisons); the same letter indicates no significant difference (p > 0.05). Each treatment group has n=8.

[0070] The results showed that the experimental group of 8 pairs of sows exhibited the best effects in increasing serum oxytocin and prolactin levels and shortening labor. In the early stage, the combination of *Bacillus pumilus* and *Streptococcus thermophilus* allowed *Bacillus pumilus* to secrete antimicrobial lipopeptides, directly inhibiting low-grade inflammation in the intestines and system, reducing inflammatory factor levels, and thus protecting the synthesis and reserves of oxytocin and prolactin. *Streptococcus thermophilus* produced lactic acid, regulating intestinal pH, promoting the proliferation of beneficial bacteria, improving intestinal mucosal barrier function, and reducing endotoxin (LPS) entry into the bloodstream, creating a favorable internal environment for normal prolactin secretion. In the later stage, high-dose *Bacillus amyloliquefaciens* provided sufficient amino acid precursors and reduced labor stress; both combined to promote the large-scale synthesis and release of oxytocin and prolactin. High levels of oxytocin enhanced the rhythmic contractions of uterine smooth muscle, accelerating fetal expulsion and significantly shortening labor. Simultaneously, the increase in prolactin prepared the body for postpartum lactation.

[0071] Results from other experimental groups showed that in group 10, where the three bacteria were used in combination throughout the entire process, long-term coexistence may have led to metabolic antagonism, resulting in insufficient anti-inflammatory effects in the early stage and insufficient absorption promotion in the later stage. In groups 4-7, the pattern of key strains was missing in at least one stage, resulting in higher maternal stress levels in the early stage, suppression of hypothalamic-pituitary axis function, insufficient hormone secretion potential in the later stage, limited improvement in feed nutrient digestibility and absorption, and insufficient supply of hormone synthesis precursors. At the same time, metabolic competition among the bacteria further weakened the absorption promotion effect.

[0072] In summary, the phased targeted strategy adopted in experimental group 8 (adding 150 mg / kg Bacillus pumilus and 150 mg / kg Streptococcus thermophilus to the diet in the early stage, and adding 300 mg / kg Bacillus amyloliquefaciens to the diet in the later stage) can more effectively activate the neuroendocrine function of the mother, thereby optimizing serum oxytocin and prolactin levels and significantly shortening the labor process. At the same time, this strategy also achieved the best overall balance among the treatment groups in key production performance indicators such as live piglet count, litter weight, birth weight, stillbirth rate, IUGR rate, and piglet uniformity.

[0073] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A staged combined feed additive for improving sow reproductive performance, characterized in that, The phased combined feed additives include a phase one feed additive and a phase two feed additive. The Phase 1 feed additive includes Bacillus pumilus preparations and Streptococcus thermophilus preparations; the Phase 2 feed additive includes Bacillus amyloliquefaciens preparations. Phase 1 refers to the period from day 1 to day 84 of pregnancy, and Phase 2 refers to the period from day 85 of pregnancy to delivery. The preservation number of the Bacillus amyloliquefaciens is: CCTCC NO: M2015359.

2. The staged combined feed additive as described in claim 1, characterized in that, The viable count of the Bacillus pumilus preparation is ≥6.0 × 10⁻⁶. 9 CFU / g, the viable count in the thermophilic streptococcal preparation is ≥6.0×10⁻⁶. 9 CFU / g.

3. The staged combined feed additive as described in claim 1, characterized in that, The viable count of the Bacillus amyloliquefaciens preparation is ≥6.0 × 10⁻⁶. 9 CFU / g.

4. The staged combined feed additive as described in claim 2, characterized in that, The dosage of the Bacillus pumilus preparation in feed is 150 mg / kg; the dosage of the Streptococcus thermophilus preparation in feed is 150 mg / kg.

5. The staged combined feed additive as described in claim 3, characterized in that, The dosage of the Bacillus amyloliquefaciens preparation added to the feed is 300 mg / kg.

6. The use of a feed additive according to any one of claims 1-5 in the preparation of feed to improve the reproductive performance of sows.

7. The application as described in claim 6, characterized in that, The improvement of sow reproductive performance includes the following aspects: (1) Improve the birth weight and uniformity of piglets; (2) Reduce IUGR rate and stillbirth rate; (3) Shorten labor and enhance lactation.

8. A staged combined feed for improving sow reproductive performance, characterized in that, The phased combined feed includes a phase one feed and a phase two feed; The Phase 1 feed consists of the following components: 0.015% of the total feed weight of Bacillus pumilus preparation, 0.015% of the total feed weight of Streptococcus thermophilus preparation, and the remainder of corn-soybean meal diet. The Phase 2 feed consists of the following components: 0.03% of the total feed weight of Bacillus amyloliquefaciens preparation, and the remainder of a corn-soybean meal diet; Phase 1 refers to the period from day 1 to day 84 of pregnancy, and Phase 2 refers to the period from day 85 of pregnancy to delivery. The preservation number of the Bacillus amyloliquefaciens is CCTCC NO: M2015359.

9. The method for feeding pregnant sows with the feed according to claim 8, characterized in that, In the first stage, the animal was fed the first stage feed at a rate of 1.5 kg / head per day. In Phase Two, the animal is fed Phase Two feed at a rate of 2.5 kg / head per day.

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