Source: TEXAS A&M UNIVERSITY submitted to NRP
MODULATION OF BENEFICIAL GUT MICROBIOTA IN POULTRY BY PHOTOPERIOD AND MONOCHROMATIC LIGHTING
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
COMPLETE
Funding Source
Reporting Frequency
Annual
Accession No.
1015997
Grant No.
(N/A)
Cumulative Award Amt.
(N/A)
Proposal No.
(N/A)
Multistate No.
(N/A)
Project Start Date
May 11, 2018
Project End Date
Sep 30, 2020
Grant Year
(N/A)
Program Code
[(N/A)]- (N/A)
Recipient Organization
TEXAS A&M UNIVERSITY
750 AGRONOMY RD STE 2701
COLLEGE STATION,TX 77843-0001
Performing Department
Poultry Science
Non Technical Summary
It has been well documented that microbiota acquired in early life plays an outsized role in establishing the gut health trajectory in later life. Therefore, approaches to manipulate and "seed" the early gut microbiota, including probiotic usage, have been of great interest. To date, no cost-effective microbiota-modulators have been discovered that can replace antibiotic growth promoters (AGPs). Furthermore, future solutions need to consider both human health concerns (antibiotic-resistant strains), and social considerations (ethical treatment of animals, welfare) even as we strive towards sustainable animal production.Therefore, there is a desperate need for solutions that offer scientifically-backed solutions that are economical and scalable. Modulation of the gut microbiota colonization by photoperiods, or using monochromatic light is, therefore, potentially important and crucial avenues. And especially if gut microbiota profiles modulated this way can be used as a means to control or influence the outcomes of intestinal infections, such as necrotic enteritis.In our previous work, we showed that chicken raised under different photoperiods acquire significantly different microbiota. However, that study only examined the first three weeks of life - a period where colonization of the gut is ongoing. However, our previous work did not answer whether such differences in microbiota are sustained beyond the early life, colonization period and if so whether they translate into benefits for fighting against intestinal pathogens. In this current study, we will compare the trajectories of broiler gut microbiota beyond the first three weeks and will span almost the entire life of modern broilers leading up to slaughter (7-8 weeks).
Animal Health Component
30%
Research Effort Categories
Basic
50%
Applied
30%
Developmental
20%
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
3113299108050%
3073299110350%
Goals / Objectives
A healthy gut microflora is recognized for its crucial role in maintenance of gut health, metabolic, and immune homeostasis. As poultry production has moved to antibiotic-free models, approaches to sustain gut health are desperately needed. One of the long term goals of our research program is to enable innovative solutions for improved poultry health through modulation of the gut microbiota. Towards this end, we have conducted studies to evaluate the role of photoperiods in establishing and maintaining beneficial gut microflora. Our short term goals are to identify photoperiod regimens and monochromatic light as a means to promote the colonization of beneficial gut microbiota. This is based on emerging studies, and also our preliminary data, which show that normal photoperiods promote strong circadian rhythms, and enable colonization by beneficial bacteria, compared extended photoperiods. Our central hypothesis is that photoperiods and light frequencies can be used to modulate the membership of the microflora early in life, which sets the tone for improved gut health in later life. To address this hypothesis, we will test two specific objectives.Objective 1: To characterize the gut microbiota under normal versus extended photoperiods, in association with necrotic enteritis occurrence in broilers. We will raise three replicate broiler flocks under two photoperiod regimens and characterize cecal microbiota using 16s rRNA amplicon sequencing.Objective 2: To characterize gut microbiota colonization in broilers exposed to monochromatic light. Hatch-day broilers will be raised under white versus blue monochromatic light in 12-hour light-dark photoperiods to determine their influence on gut microbiota colonization and diversity. We will also evaluate these treatments and their relationship to occurrence of necrotic enteritis.
Project Methods
We will achieve our objectives through a combination of live-animal trials under different photoperiods, in combination with molecular approaches to characterize gut microbiota membership, as well as occurrence of necrotic enteritis. The live animal studies, sampling of birds for microbiota analysis will be designed, coordinated and carried out by the Athrey lab (PI). Tissues collected for analysis of necrotic enteritis diagnosis will be carried out by the lab of Dr. Audrey McElroy (co-I). All live-animal work will be carried out at the Texas A&M Poultry Research and Education center, whereas molecular and computational work will be carried out in the department of poultry science labs at the Kleberg building.If as we hypothesize, the colonization of beneficial microbiota can be modulated by photoperiods, we would expect to see a) significantly different microbiota communities between normal (beneficial) and extended photoperiods (not-beneficial), and b) that beneficial gut microbiota composition is associated with lower incidence of necrotic enteritis.Objective 1: To characterize the gut microbiota under normal versus extended photoperiods, in association with necrotic enteritis occurrence in broilers. Study design: We will raise two replicate flocks of 36 commercial broilers for each of three photoperiod treatments, namely - 12L/12D, 18L/6D, and 23L/1D, starting with hatch-day old chicks. The birds will be placed on identical ad libitum feed (commercial broiler feed), on a three phase diet (starter, grower finisher). Daylight conditions will be replicated by using dimmable LED lamps. The beginning and end of a light period, the lights will be dimmed to 500 lux for 10 minutes prior to complete darkness, while daylight intensity at 1300 lux. We will sample birds from three time points (3 week, 5 week and 7 week), to assay the gut microbiota and to assess occurrence of necrotic enteritis. Ten birds from each replicate pen will be euthanized at every sampling time points (10 birds x 2 replicates x 3 treatments x 3 time points = 180 birds) and included in analyses. With this approach we will have 20 individual microbiota profiles per treatment and time point, which will provide us with sufficient power to distinguish community differences (40).Microbiota analyses: We will isolate DNA from cecal content using the MoBio PowerFecal kit according to the manufacturer's instructions. 20 ng of purified DNA will be used for PCR amplification of bacterial 16S rRNA gene sequences, using Q5â High-Fidelity DNA polymerase (NEBNextâ High-Fidelity 2X PCR Master Mix, New England BioLabs, Ipswich, MA). A nested PCR design will be used to amplify the V4 variable region of the 16s rRNA gene, followed by addition of Illumina sequencing primersand Illumina indexes. The amplicons will be sequenced on an Illumina MiSeq platform (Illumina, San Diego, CA) using the paired-end mode. Raw data will be processed and analyzed using the Mothur tool (41) for microbiota analysis.Necrotic Enteritis diagnosis: Diagnosis of necrotic enteritis will be performed on tissue from the small intestine (ileum/jejunum). Diagnosis will be based on presence of gross lesions, and gram stained smear of the mucosal lining. As these tissues will be collected upon planned euthanasia, we can assure that the tissue and lesions are not artefacts of degradation (42). These diagnoses will be performed by the lab of Dr. McElroy.Objective 2: To characterize gut microbiota colonization in broilers exposed to monochromatic light. Study design: We will raise two replicate flocks of 36 commercial broilers for each of three light treatments, namely - standard white lighting at 1300 lux, and blue light (450-480nm), both on a 12/12 LD rotation, and a third blue light treatment with a photoperiod of 18/6 LD. It has been shown that blue light helps chicken stay calm, and may provide welfare benefits (34). The birds will be placed on identical ad libitum feed (commercial broiler feed), on a three phase diet (starter, grower finisher). We will sample birds from three time points (3 week, 5 week and 7 week), to assay the gut microbiota and to assess occurrence of necrotic enteritis. Ten birds from each replicate pen will be euthanized at every sampling time points (10 birds x 2 replicates x 3 treatments x 3 time points = 180 birds) and included in analyses. With this approach we will have 20 individual microbiota profiles per treatment and time point, which will provide us with sufficient power to distinguish community differences (40).Analysis of circadian rhythms: From the euthanized birds, we will isolate peripheral brain tissue to assay the expression of circadian genes (CLOCK, BMAL1, and PER3) to determine if white and blue light are equivalent in their ability to reinforce circadian rhythms, and hence have a similar basis for regulating host homeostasis. Microbiota analyses: We will isolate DNA from cecal content using the MoBio PowerFecal kit according to the manufacturer's instructions. 20 ng of purified DNA will be used for PCR amplification of bacterial 16S rRNA gene sequences, using Q5â High-Fidelity DNA polymerase (NEBNextâ High-Fidelity 2X PCR Master Mix, New England BioLabs, Ipswich, MA). A nested PCR design will be used to amplify the V4 variable region of the 16s rRNA gene, followed by addition of Illumina sequencing primersand Illumina indexes. The amplicons will be sequenced on an Illumina MiSeq platform (Illumina, San Diego, CA) using the paired-end mode. Raw data will be processed and analyzed using the Mothur tool (41) for microbiota analysis.Necrotic Enteritis diagnosis: Diagnosis of necrotic enteritis will be performed on tissue from the small intestine (ileum/jejunum). Diagnosis will be based on presence of gross lesions, and gram stained smear of the mucosal lining. As these tissues will be collected upon planned euthanasia, we can assure that the tissue and lesions are not artefacts of degradation (42). These diagnoses will be performed by the lab of Dr. McElroy.Analysis of data:Following generation of data on Necrotic Enteritis occurrence, and microbiota profiles, we will carry out multivariate analyses to determine if and how microbiota membership are associated with enteritis outcomes. Example analyses will include the estimating the odds that the presence or absence of a certain taxon (or Operational Taxonomic Unit) is associated with risk of necrotic enteritis. We will use a model selection approach to determine whether the presence/absence, or the abundance of specific taxa are influential on NE outcomes. Finally, we will also test the hypothesis of whether necrotic enteritis selects for a certain microbiota community, which would indicate that occurrence of NE influences microbiota structure instead of vice versa. Our temporal data will help resolve if and when such changes are occurring.

Progress 05/11/18 to 09/30/20

Outputs
Target Audience: Poultry producers, poultry veterinarians, gut health researchers, and the broader biomedical science community. Changes/Problems: Our original plans were slightly altered due to difficulties getting reliable instances of necrotic enteritis in our model. However, we proceeded with the planned work and generated other insights that were possible with the full extent of the data. We also extended the studies beyond the original scope by carefully designing our experiments and this led to new insights about the role of monochromatic lighting on modulating gut microbiota and immune responses. What opportunities for training and professional development has the project provided? Overall, these funds were used in the training of three PhD students in my lab, and indirectly in the dissertation projects of two other PhD students. In all these cases, multiple undergraduate researchers participated in circadian experiments and obtained valuable live-animal and lab based training. How have the results been disseminated to communities of interest? Results were published in peer-reviewed journals and presented at international conferences. What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? These studies led to new knowledge and valuable information about the maturation and modulation of the chicken gut microbiota. 1. We verified that chicken gut microbiota assembly is influenced by the photoperiod. 2. We were unable to obtain high-quality data on necrotic enteritis, but regardless, these studies helped investigate various new aspects of chicken gut microbiota and immune development. 3. We performed lighting experiments (replicated) which show that the monochromatic lighting has a differential impact on splenic gene expression in chicken embryos, which translated into differential microbiota assembly post-hatch, and in turn the were associated with different responses to vaccination. 4. We were able to use part of the funds to perform other chicken microbiota studies, which were successfully completed and published.

Publications


    Progress 10/01/19 to 09/30/20

    Outputs
    Target Audience:Poultry producers, poultry veterinarians, gut health researchers, and the broader biomedical science community. Changes/Problems:Our original plans were slightly altered due to difficulties getting reliable instances of necrotic enteritis in our model. However, we proceeded with the planned work and generated other insights that were possible with the full extent of the data. What opportunities for training and professional development has the project provided?Overall, these funds were used in the training of three PhD students in my lab, and indirectly in the dissertation projects of two other PhD students. In all these cases, multiple undergraduate researchers participated in circadian experiments and obtained valuable live-animal and lab based training. How have the results been disseminated to communities of interest?Results were published in peer-reviewed journals and presented at international conferences. One manuscript is under review and one more is in preparation. What do you plan to do during the next reporting period to accomplish the goals?Wrap up the remaining manuscript and submit for publication.

    Impacts
    What was accomplished under these goals? These studies led to new knowledge and valuable information about the maturation and modulation of the chicken gut microbiota. 1. We verified that chicken gut microbiota assembly is influenced by the photoperiod. 2. We were unable to obtain high quality data on necrotic enteritis, but regardless, these studies helped investigate various new aspects of chicken gut microbiota and immune development. 3. We performed lighting experiments (replicated) which show that the monochromatic lighting has differential impact on splenic gene expression in chicken embryos, which translated into differential microbiota assembly post-hatch, and in turn the were associated with different responses to vaccination. 4. We were able to use part of the funds go perform other chicken microbiota studies, which were successfully completed and published.

    Publications

    • Type: Journal Articles Status: Published Year Published: 2019 Citation: Hubert SM, Al-Ajeeli M, Bailey CA, Athrey G (2019) The role of housing environment and dietary protein source on the gut microbiota of chicken. Animals?: an open access journal from MDPI, 9.
    • Type: Journal Articles Status: Published Year Published: 2020 Citation: Nelson JR, Ibrahim M, Sobotik EB, Athrey G, Archer GS (2020a) Effects of yeast fermentate supplementation on cecal microbiome, plasma biochemistry and ileal histomorphology in stressed broiler chickens. Livestock science, 104149.
    • Type: Journal Articles Status: Published Year Published: 2020 Citation: Williams T, Athrey G (2020) Cloacal Swabs Are Unreliable Sources for Estimating Lower Gastro-Intestinal Tract Microbiota Membership and Structure in Broiler Chickens. Microorganisms.
    • Type: Journal Articles Status: Published Year Published: 2018 Citation: Hieke A-SC, Hubert SM, Athrey G (2019) Circadian disruption and divergent microbiota acquisition under extended photoperiod regimens in chicken. PeerJ, 7, e6592.


    Progress 10/01/18 to 09/30/19

    Outputs
    Target Audience: Nothing Reported Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?The student working on this project (Mohamed Ibrahim)was trained to perform all aspects of the lab and computational steps for the analysis. The student was trained by another senior student (Shawna Hubert) who graduated in 2019. She was supported breifly these funds.This approach benefited both the students - by offering a mentoring experience to Dr. Hubert and to Mr. Ibrahim. Mr. Ibrahim has been able to use this new expertise and apply to his own PhD research (on monochromatic lighting). he presented one of his studies at the Poultry Science Association meeting in Montreal in summer 2019. 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?We plan to finalize the analysis and synthesis of results from Objective1 and prepare the data for dissemination. We plan to complete the remaining steps for generating the data for Objective 2 (sequencing and analysis) and will be completing these aspects as well in this project year.

    Impacts
    What was accomplished under these goals? At this time, we havecompleted live animal studies to address both the objectives in this study. The samples generated from both these studies were collected as described in the study protocols and stored for the microbiota assays. For objective 1, the samples collected were processed - first by isolation of DNA from cecal samples. High-quality DNA isolates were then used in amplification reactions targeting the 16S rRNA gene (V4 region). The amplicon pools were then submitted to sequencing and the data was received late in 2019. Graduate student Mohamed Ibrahim is performing the data analysis and we hope to have results synthesized and written up for publication in early 2020. For objective 2, the samples have been collected and stored and are being processed. Once all the samples have been processed, they will be assayed and analyzed using the same molecular and computational approaches as applied for Objective 1.

    Publications

    • Type: Journal Articles Status: Published Year Published: 2019 Citation: Hieke AC, Hubert SM, Athrey G. 2019. Circadian disruption and divergent microbiota acquisition under extended photoperiod regimens in chicken. PeerJ 7:e6592 https://doi.org/10.7717/peerj.6592
    • Type: Conference Papers and Presentations Status: Published Year Published: 2019 Citation: Mohamed Ibrahim*1,2, Jill Nelson1, Greg Archer1, and Giri Athrey1. Effects of monochromatic lighting and In ovo vaccination on the splenic transcriptome profiles of chicken.


    Progress 05/11/18 to 09/30/18

    Outputs
    Target Audience: Nothing Reported Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Undergraduate students have been trained with experiments. Graduate students Shawna Hubertand Mohamed Ibrahim have been supported through this grant and Mohamed Ibrahim has been working on the experiments and being trained in all the downstream protocols (RNA isolation, library preparation, 16s data analysis). 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 the next reporting period, we will complete the analysis of the data from the first live animal experiment we ran. Also in the next reporting period, we will perform the second live animal study and begin synthesizing the results.

    Impacts
    What was accomplished under these goals? This is a new project started in April. Still awaiting results from initial experiments.

    Publications