Source: UNIV OF CONNECTICUT submitted to NRP
EFFECTS OF IN-OVO PROBIOTIC SUPPLEMENTATION ON MUSCLE GROWTH AND PERFORMANCE IN BROILERS
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
COMPLETE
Funding Source
Reporting Frequency
Annual
Accession No.
1021834
Grant No.
2020-67016-30817
Cumulative Award Amt.
$200,000.00
Proposal No.
2019-05870
Multistate No.
(N/A)
Project Start Date
May 15, 2020
Project End Date
May 14, 2024
Grant Year
2020
Program Code
[A1231]- Animal Health and Production and Animal Products: Improved Nutritional Performance, Growth, and Lactation of Animals
Recipient Organization
UNIV OF CONNECTICUT
438 WHITNEY RD EXTENSION UNIT 1133
STORRS,CT 06269
Performing Department
Animal Science
Non Technical Summary
Over the last few decades, there has been an increasing demand for poultry meat as a good protein source in the diet. To meet this demand, the poultry industry initiated several strategies to increase broiler meat production. One among them was the inclusion of antibiotics in the broiler diet. In effect, use of antibiotics as growth promoters (AGPs) helped improve bird health, growth and performance. However, use of antibiotics as feed additives led to concerns of antibiotic resistant pathogens and their implications to human health. Consequently, the FDA has curbed the use of AGPs in food animals including poultry. This restriction led to problems with performance, increased production costs and rise in diseases in poultry. Therefore, there is a need to develop effective alternatives to help promote health and performance in broilers. Among the different alternatives tested, feeding probiotics to chickens was shown to improve body weight gain and feed conversion ratio in chickens. In modern-day broilers, the period of embryonic growth accounts for almost half of the lifespan. Also, this period of development is critical to chick performance following hatch. Hence, any approach that can support and promote embryo growth is expected to have a positive impact on performance in broilers. Specifically, this study will apply probiotics on eggs and study their effect on embryonic growth and performance in broilers. Additionally, this study will focus on muscle growth since muscle mass is directly related to meat production. It is expected that this study will help demonstrate the potential for targeting broiler embryos to improve production in these birds. Overall, use of probiotics to improve growth and their application on eggs may serve as a novel and effective strategy for raising broilers in light of the AGP ban.
Animal Health Component
40%
Research Effort Categories
Basic
60%
Applied
40%
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
30532201020100%
Knowledge Area
305 - Animal Physiological Processes;

Subject Of Investigation
3220 - Meat-type chicken, live animal;

Field Of Science
1020 - Physiology;
Goals / Objectives
Increasing concerns over antibiotic use in food animals and the emergence of antibiotic-resistant pathogens led to the FDA directive curbing AGP use in poultry production. Thus, there is a critical need for an effective alternative to promote poultry health and performance. Several researchers have demonstrated the potential for dietary supplementation of probiotics in day-old chicks on improving growth performance in broiler chicken. However, the period of embryonic and neonatal development accounts for almost 50% of the productive life of modern broilers and is critical to attaining quality performance at marketing. Hence, the overall goal of this study is to promote embryonic growth as a means to improve post-hatch growth in broilers.The specific objectives of this study are:1. To determine the effects of early probiotic administration on muscle growth and performance in broiler chickens.2. Identify candidate genes and pathways mediating the beneficial effects of probiotic supplementation on muscle growth in broilers.
Project Methods
Probiotic cultures: Probiotic strains (L. paracasei DUP 13076 - Lp and L. rhamnosus NRRL-B-442 - Lr) will be cultured separately in de Mann, Rogosa, Sharpe broth at 37°C for 24 h. Appropriate dilutions of the single strains in PBS will be used to obtain the desired level of inoculum (8 log CFU/egg).Experimental design, egg incubation and hatching: The study will be performed at the UConn poultry research unit. Ross 308 eggs (n=1100) will be obtained from a local commercial farm. All settable eggs will be weighed (starting egg weight), numbered and randomly assigned to the treatment groups (360 eggs/group). Group 1: Eggs sprayed with PBS (vehicle control), Group 2: Eggs sprayed with Lp, Group 3: Eggs sprayed with Lr. Eggs will be sprayed with 200 μl of the probiotic treatment strain (~8 log CFU/egg) or PBS (solvent control) on ED 0. Sprayed eggs will be incubated for 18 days at 37.5-37.8°C and 55-60% RH (Upadhyaya et al., 2015). On day 18, eggs will be transferred to the hatcher (36.8 to 37°C and 65 to 70% RH) for 3 days or until hatch. Throughout the study, eggs in different groups will be placed in separate incubators to avoid cross-contamination.Embryo morphometric measurements: Thirty-five eggs per group will be randomly sampled on ED 7, 10, 14, and 18. The eggs will be weighed and opened through the blunt end. Starting on ED 14, the embryos will be euthanized by cervical dislocation and dissected to obtain embryo weight, yolk sac weight, breast muscle weight and cross-sectional area (de Oliveira et al., 2014). Relative embryo and yolk weights will be normalized to the starting egg weight.Embryo sexing: Leg muscle sections will be collected at each sampling time for RNA extraction and qRT-PCR. Relative quantification of CHD-Z specific sequence and CHD-ZW common sequence will be normalized to the GAPDH gene. Males (ZZ) and females (ZW) will be identified based on the expression level ratio of CHD-ZW/CHD-Z. Sexual identity of the embryo will be matched back to the egg number and incorporated as metadata for statistical analysis.Hatchling morphometric measurements: On day of hatch (day 21), percent hatchability will be recorded. Thirty-five hatchlings from each group will be sacrificed and live weight, total breast muscle CSA and relative breast weight will be recorded (Aravind et al., 2003; Scheuermann et al., 2004).Broiler chicken management: Hatchlings (n=160/ group) will be sexed, weighed and tagged. Broiler chicks will be started on a 23% CP, 3000 kcal/kg ME ration and then placed on a 20% CP, 3200 kcal/kg grower/finisher ration at 3 weeks of age. Prior to feeding, individual body weights will be obtained on weeks 1-5. Feed consumed will be recorded daily on a per pen basis, uneaten food will be collected once daily before morning feeding and FCR will be calculated (Kalavathy et al., 2003).Breast weight and carcass yield percentages: On d 3, 7 (wk 1), 21 (wk 3) and 35 (wk 5) post-hatch, 35 birds from each group will be sacrificed. Head and feet will be removed, followed by defeathering and evisceration so that the carcass will be in a ready to cook (RTC) state. Dressing percentage, total breast muscle CSA, relative breast weight and relative leg weight will be recorded (Sarangi et al., 2016). Muscle collection and processing: At each sampling time [ED 10 to wk 5], breast muscle sections (n=35/embryos/birds per group) will be collected, embedded in Tissue-Tek OCT and frozen in dry ice-cooled isopentane (Al-Musawi et al., 2011; Reed et al., 2014). Additionally, samples for transcriptome analysis will be flash frozen in liquid nitrogen (Kong et al., 2017; Li et al., 2019). All samples will be stored at -80°C until further use.Muscle histology and immunostaining: Breast muscles samples (ED 10 to wk 5) embedded in OCT will be cut to 10μm thickness using a microtome cryostat and mounted to glass slides (Reed et al., 2014). Muscle sections will be immunostained using a mouse monoclonal antibody against chicken Pax7 and rabbit polyclonal antibody against laminin followed by Alexa Fluor 488 goat anti-mouse IgG and Alexa Fluor 546 goat anti-rabbit IgG, allowing visualization of Pax7(+) satellite cells and fiber membranes. Nuclei will be detected with Hoechst 33258 (Kawakami et al., 1997; Day et al., 2009). At least 25 images will be obtained from 5 different sections of each muscle sample to quantify muscle fiber density (Scheuermann et al., 2004; Halevy et al., 2004; Reed et al., 2014; Liu et al., 2010). Fiber CSA will be measured as the region within the fiber boundary using the area measurement tool in ImageJ. Total myofiber number will be calculated by multiplying the average MFD per animal by the overall muscle CSA. The number of Pax7+ nuclei associated with the myofiber and the total number of Hoechst-stained myonuclei will be counted to determine satellite cell and total nuclei numbers (Halevy et al., 2004).Statistical analysis: A completely randomized design with factorial treatment structure will be followed. Data from morphometric measurements and muscle analysis will be sorted by age and sex and analyzed using the PROC MIXED procedure of SAS followed by Tukey post hoc test to examine statistical differences between means of different groups. Significant difference will be determined at P ≤ 0.05.RNA extraction and transcriptome sequencing: At each sampling time (ED 10 to wk 5), breast muscle sections will be harvested from 12 embryos/chicks (6 male and 6 female) per treatment group for transcriptome analysis. Briefly, RNA will be extracted from the harvested samples and their quality assessed on an Agilent 2100 Bioanalyzer (Li et al., 2019; Kong et al., 2017; Hoffman et al., 2016). For transcriptome sequencing, total cellular RNA will be rRNA-depleted, fragmented and whole transcriptome library will be constructed using the the Illumina Tru-seq paired-end (PE) RNA-seq kit. Each library will be sequenced on the Illumina NextSeq 500 (in house). We will perform PE reads of 75bp x 35bp for each library and run each on one flow lane to obtain ~80 million mappable reads (~160 million paired) per sample to ensure capture of transcripts to 0.006 copy sensitivity. We will perform biological replicates (12 eggs/hatchlings per treatment) at each time point, including validation and downstream sequencing, to strengthen statistical support for differential transcription.Transcriptome analysis: Briefly, low quality bases and duplicate reads will be removed using PRINSEQ (Schmieder and Edwards, 2011). The reads will be mapped to the chicken reference transcriptome using HISAT2 (Kim et al., 2015). Transcript abundance levels will be estimated using the IsoEM2 expectation-maximization algorithm (Nicolae et al., 2011) and differentially expressed genes will be identified using the IsoDE2 bootstrapping framework developed by Dr. Mandoiu (Mandric et al., 2017). Additionally, Database for Annotation, Visualization, and Integrated Discovery (DAVID) will be used to identify gene functional annotation terms that are significantly enriched in particular gene lists with the whole chicken genome as the background (Huang et al., 2009). DAVID will calculate a modified Fishers Exact P-value to demonstrate Gene Ontology (GO) and KEGG molecular pathway enrichment, where P-values less than 0.05 after Benjamini multiple test correction will be considered to be strongly enriched in the annotation category. Differential expression will be confirmed by RT-qPCR on a selection of 10-20 regulated transcripts (two-fold or more vs. respective control) to validate transcriptional profile across datasets.

Progress 05/15/20 to 05/14/24

Outputs
Target Audience:The target audiences for this project included undergraduate and graduate students, poultry producers, poultry industry and the scientific community. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?As part of this project, graduate students were engaged in conducting poultry trials, necropsy, sample collection, tissue processing for histology and transcriptome sequencing. In addition to the wet lab experiments, the graduate student also performed statistical analysis on the data. Additionally, an undergraduate student was trained in muscle sectioning, staining and imaging procedures. Besides lab work, graduate student was also training on scientific communication (writing, oral), grant writing, experimental design and project management. The student also had the opportunity to present their research to the poultry community including industry, academia, students and regulators. How have the results been disseminated to communities of interest?Results from the study were shared with academics, regulators and the poultry industry through presentations at PSA Annual meetings and with the scientific community through publication of a peer-reviewed manuscript. What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? Increasing concerns over antibiotic use in food animals and the emergence of antibiotic resistant pathogens led to the FDA directive curbing AGP use in poultry production. Thus, there is a critical need for an effective alternative to promote poultry health and performance. In this regard, in-feed probiotic supplementation serves as an effective alternative to AGPs. However, the period of embryonic development is critical to attaining optimum production efficiency. Therefore, in-ovo probiotic supplementation could be a potential alternative to promote growth and performance in broiler chicken. Towards this, the present study investigated the effect of sustained probiotic supplementation on muscle growth and performance in broilers throughout their life span. Performance trial: Our results demonstrate that sustained probiotic supplementation significantly improved post-hatch performance in broilers (p<0.05). Specifically, L. rhamnosus and L. paracasei supplementation improved body weight gain by 15-20%, RTE (ready to eat) weight by 18-23%, breast weight by 21-27% and leg weight by 15-17% when compared to the control. In addition, probiotics also significantly lowered FCR by 4-6%. Further, we did not observe any impact of probiotic supplementation on meat quality including color, pH and cook loss. Overall, sustained supplementation of LR and LP could be used to enhance the overall growth and performance in broiler chicken. As the next step to understand how probiotics might be supporting musclr growth and meat production, we investigated myogenesis in broilers starting across the lifespan starting with developing embryos followed by chick and market-age birds. In chickens, muscle development during embryonic growth is predominantly by myofiber hyperplasia. Following hatch, muscle growth primarily occurs via hypertrophy of the existing myofibers. Since myofiber number is set at hatch, production of more muscle fibers during embryonic growth would provide a greater myofiber number at hatch and potential for post-hatch muscle growth by hypertrophy. Myogenesis in the developing embryo: We observed that in-ovo probiotic supplementation significantly improved embryo weight, breast weight and leg weight (P <0.05). Further, histological analysis of the pectoralis major muscle (PMM) revealed a significant increase in muscle fiber density (MFD) and nuclei number in the probiotic-treated embryos when compared to the control (P < 0.05). In 18-day old broiler embryos, myofibers in the treatment group had a significantly smaller cross section area (CSA; LP: 95.27 ± 3.28 μm2, LR: 178.84 ± 15.1 μm2) when compared to the control (211.41 ± 15.67 μm2). This decrease in CSA was found to be associated with a concomitant increase in MFD (fibers/mm2) in the LP (13647 ± 482.15) and LR (13957 ± 463.13) group when compared to the control (7680 ± 406.78). Myogenesis post-hatch: Our results demonstrate that sustained probiotic supplementation significantly improved muscle development throughout the post-hatch phase (p<0.05). Specifically, at hatch and week 1 post hatch, we observed significantly higher MFD in the probiotic-treated chicks. For instance, at week 1 post-hatch, PMM from LR and LP supplemented chicks had a 34-52% higher MFD when compared to the control. As the grow-out period progressed, we observed an increase in muscle growth as evidenced by hypertrophy and increase muscle fiber CSA. At market age (week 6), myofiber CSA in the probiotic groups was ~10% larger than in the control. Additionally, this increase in myofibrillar hyperplasia (in-ovo) and hypertrophy (post-hatch) in the treatment groups was associated with upregulation in the expression of key genes regulating muscle growth including MYF5, MYOD, MYOG and IGF-1. In summary, sustained probiotic supplementation promoted overall embryo growth, muscle development and performance in broilers.

Publications

  • Type: Journal Articles Status: Published Year Published: 2023 Citation: Muyyarikkandy, M.S., Schlesinger, M., Ren, Y., Gao, M., Liefeld, A., Reed, S. and Amalaradjou, M.A., 2023. In ovo probiotic supplementation promotes muscle growth and development in broiler embryos. Poultry Science, 102(7), p.102744.


Progress 05/15/22 to 05/14/23

Outputs
Target Audience:The target audiences for this project include students in agricultural sciences who will be mentored throughout the duration of the project, the poultry industry and the scientific community. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?During this reporting period, graduate students were engaged in conducting the poultry trials, necropsy, sample collection and tissue processing for histology and transcriptome sequencing. In addition to the wet lab experiments, the graduate student also performed statistical analysis on the data. Additionally, currently an undergraduate student is being trained on muscle sectioning, staining and imaging procedures. How have the results been disseminated to communities of interest?Results from the study were shared with academics, regulators and the poultry industry through presentations at the 2022 PSA Annual meeting and with the scientific community through publication of a peer-reviewed manuscript. What do you plan to do during the next reporting period to accomplish the goals?In continuation of the proposed research activities, additional muscle sections (post-hatch) will also be processed and imaged to study muscle growth in terms of fiber number, fiber diameter and nuclear density. Further, muscle sections will be subjected to transcriptome sequencing to characterize gene level changes in muscle growth as influenced by the probiotic supplementation.

Impacts
What was accomplished under these goals? During this report period, 180 one-day old Ross 308 chicks were randomly assigned to three groups (104 birds/group). The probiotic groups received a daily in-feed supplementation of either L. paracasei (LP) or L. rhamnosus (LR; 9 log CFU/g feed) for the entire duration of the study while the control received none. On day of hatch, week 1, week 3, and week 6, ten birds were sacrificed, breast yield was recorded and pectoralis major muscle (PMM) was collected for histology. Muscle sections were stained and imaged to quantify muscle fiber density (MFD, MF/mm2), myofiber cross-sectional area (CSA), and nuclei density. The study was set out as a completely randomized design and data were analyzed using GraphPad (Version 9.3.1) with p<0.05 considered as significantly different. Our results demonstrate that sustained probiotic supplementation significantly improved muscle growth and breast muscle yield throughout the post-hatch phase (p<0.05). Specifically, at market age, LR and LP supplementation improved breast weight by 21-27% when compared to the control. In addition, probiotic supplementation consistently resulted in smaller CSA and increased MFD and nuclei number in the PMM of these birds. For instance, in the hatchling, myofiber density in the probiotic groups was 67-71 MF/mm2 when compared to 52 MF/mm2 in the control. In summary, probiotics promoted muscle growth and development thereby improving meat yield in broilers.

Publications

  • Type: Journal Articles Status: Awaiting Publication Year Published: 2023 Citation: Muyyarikkandy MS, Schlesinger M, Ren Y, Gao M, Leifeld A, Reed S, Amalaradjou MA. 2023. In ovo probiotic supplementation promotes muscle growth and development in broiler embryos. Poult Sci. In Press. https://doi.org/10.1016/j.psj.2023.102744.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2022 Citation: Yuying Ren, Mairui Gao, Ragini Reddyvari, Si Lu, Mary Anne Amalaradjou. 2022. Sustained probiotic supplementation promotes growth and performance in broiler chickens. 2022 Annual Meeting Abstracts - Poultry Science Vol. 101 (E-suppl. 1). https://poultryscience.org/files/galleries/2022_Abstract_Book.pdf


Progress 05/15/21 to 05/14/22

Outputs
Target Audience:The target audiences for this project include students in agricultural sciences who will be mentored throughout the duration of the project, the poultry industry and the scientific community. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?During this reporting period, graduate students were engaged in conducting the poultry trials, necropsy, sample collection and tissue processing. In addition to the wet lab experiments, the graduate student also performed statistical analysis on the data. Additionally, currently an undergraduate student is being trained on muscle sectioning, staining and imaging procedures. How have the results been disseminated to communities of interest? Nothing Reported What do you plan to do during the next reporting period to accomplish the goals?In continuation of the proposed research activities, additional experiments will be set up to evaluate the efficacy of probiotic supplementation on muscle growth and performance. Additionally, tissue samples will be processed for embryo sexing via PCR. Muscle sections (Post-hatch) will also be processed and imaged to study muscle growth in terms of fiber number, fiber diameter and nuclear density. Further, muscle sections will be subjected to transcriptome sequencing to characterize gene level changes in muscle growth as influenced by the probiotic supplementation.

Impacts
What was accomplished under these goals? During this report period, in vivo trial was conducted to evaluate the effect of in ovo probiotic application on broiler growth and performance. Fertile eggs for the trial were obtained through help with our collaborator at Aviagen. Probiotics were sprayed on to eggs and set up for incubation and hatching. Hatchlings were then transferred to floor pens and reared until week 6 with/ without in-feed supplementation of the respective probiotic treatments. Overall, early and sustained probiotic supplementation was associated with an increase in weight gain and muscle mass and improvement in FCR. Also, at this time we have processed muscle samples from broiler embryos from d14 to d18 of embryonic growth. This data indicates that in-ovo probiotic supplementation increased muscle fiber number in the treated embryos when compared to the control. This is indicative of the growth promoting ability of the probiotics with specific relevance to muscle growth.

Publications


    Progress 05/15/20 to 05/14/21

    Outputs
    Target Audience:During this reporting period, graduate students were trained in conducting poultry trials, necropsy, sample collection and tissue processing. Changes/Problems:The impact of COVID and research ramp down led to a significant delay in the study. Specifically, inability of research personnel to come to campus delayed project initiation and research progress. What opportunities for training and professional development has the project provided?During this reporting period, graduate students were engaged in conducting the poultry trials, necropsy, sample collection and tissue processing. In addition to the wet lab experiments, the graduate student also performed statistical analysis on the data. How have the results been disseminated to communities of interest? Nothing Reported What do you plan to do during the next reporting period to accomplish the goals?In continuation of the proposed research activities, additional experiments will be set up to evaluate the efficacy of probiotic supplementation on muscle growth and performance. Additionally, tissue samples will be processed for embryo sexing via real time qPCR. Muscle sections will also be processed and imaged to study muscle growth in terms if fiber number, fiber diameter and nuclear density.

    Impacts
    What was accomplished under these goals? During this report period, in vivo trial was conducted to evaluate the effect of in-ovo probiotic application on broiler growth and performance (obj.1). Fertile eggs for the trial were obtained through help with our collaborator at Aviagen. Probiotics were sprayed on to eggs and set up for incubation and hatching. Hatchlings were then transferred to floor pens and reared until week 5 with/ without in-feed supplementation of the respective probiotic treatments. Overall, early and sustained probiotic supplementation was associated with an increase in hatchability, improved muscle area, RTC, breast and leg weight and FCR.

    Publications