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Fecal microbiota transplant is novel approach for circoviruses

Research Review: FMT may be an alternative to antimicrobials in swine production through improving nutrient digestion and immune response during respiratory infections.

December 24, 2018

6 Min Read
piglets in farrowing stall
Fecal microbiota transplantation is a potential disease control method, where pigs with diverse and beneficial gut microbiota have fewer health challenges.National Pork Board

Researchers: Megan C. Niederwerder, Laura A. Constance, Raymond R.R. Rowland and Maureen A. Sheahan, Kansas State University College of Veterinary Medicine Department of Diagnostic Medicine/Pathobiology; Waseem Abbas, Samodha C. Fernando and Thomas E. Burkey, University of Nebraska-Lincoln Department of Animal Science; Megan L. Potter, Abilene Animal Hospital PA; and Richard A. Hesse and Ada G. Cino-Ozuna, Kansas State University College of Veterinary Medicine Department of Diagnostic Medicine/Pathobiology and Veterinary Diagnostic Laboratory
The most recent analysis of the cost of porcine reproductive and respiratory syndrome virus to the United States alone is $664 million annually. Since its introduction into the United States nearly 30 years ago, the PRRS virus has cost the nation’s swine industry an estimated $14 billion in production losses.

Additionally, PRRS virus is a major contributor to animal health costs in swine production and increased antimicrobial usage in affected herds.

With increasing pressure to eliminate antimicrobial usage in food animal production, the U.S. swine industry is searching for other ways to battle such devastating viruses.

Research project at KSU
A group of researchers from Kansas State University, University of Nebraska-Lincoln and the Abilene (Kan.) Animal Hospital has discovered that fecal microbiota transplantation from sows with several high health characteristics provided significant benefits to weaned piglets co-infected with PRRS virus and porcine circovirus type 2. The principal effect of FMT in the co-infection model was to decrease the number of pigs affected by porcine circovirus associated disease.

Specifically, a 70% reduction in mortality of transplanted pigs was demonstrated. Additionally, parenteral antimicrobial treatments prescribed for clinical disease were reduced by 60% in the FMT group. Microbiome composition in transplanted pigs demonstrated an increase in several microbial families considered beneficial for gut health.

Ten pairs of barrow siblings (n = 20; 24 days of age upon arrival) were obtained at weaning from a single high-health commercial source negative for PRRS virus, Mycoplasma hyopneumoniae and porcine epidemic diarrhea virus. Sibling pairs were from 10 different sows and the piglets were not vaccinated for PCV-2. No prophylactic or therapeutic antibiotics were administered at weaning or within one week of arriving at KSU. All pigs were housed in two identical environmentally controlled rooms at the KSU Large Animal Research Center and maintained under biosafety level 2 conditions.

Each sibling pair was divided into either the control or FMT group; the two groups were balanced according to arrival weight. Pigs were housed in groups of 10 in a 9.1-square-meter pen with raised slatted flooring. All pigs were given approximately 24 hours to acclimate to their new environment prior to FMT or mock transplant treatment. Pigs were given access to food and water ad libitum.

2 donor sows
Two sows from a commercial farrow-to-wean farm in Kansas were selected as donors for the transplant material. This herd was negative for PRRS virus and had recently undergone a M. hyopneumoniae elimination program.

The two sows were selected based on several characteristics, including older age (average age 4.8 years), high parity (nine and 12 litters born prior to donation), large litters with a high percentage of born alive piglets (15.1 ± 2.0 total born; 95% born alive), low pre-weaning mortality, no history of fetal mummification and no antibiotic treatment received within at least the last 15 months prior to donation.

Pre-weaning mortality in these two sows was primarily attributed to crushing injuries. Lifetime number of weaned pigs was 101 and 131 for each sow, respectively.

For this study, feces were collected during lactation, and sows had not yet weaned their respective litters at the time. Feces were initially screened and confirmed as negative for gastrointestinal parasites using a fecal float qualitative exam by the KSU Veterinary Diagnostic Laboratory.

To prepare the FMT, fresh feces were collected naturally during defecation or manually from the rectum of the two sows. Feces were collected on a single time and day, and mixed and processed within about three hours after collection, during which the fecal microbiota was concentrated and stored.

FMT or control administered
About 24 hours after arriving at KSU, pigs were administered a fecal microbiota transplant or a mock transplant (control). Mock transplants were made of 10% glycerol in sterile saline. Transplants or mock transplants were administered as 5-ml doses delivered once daily for seven consecutive days prior to co-infection.

To administer the FMT or mock transplant, 5-ml doses were delivered through flexible dispensing tips. Solutions were delivered slowly on the tongue or in the cheek pouch, letting the pig chew on the tip and naturally consume the material over a period of 30 seconds to one minute.

At 32 days of age, all 20 pigs were infected with PRRS virus and PCV-2. Body weights of individual pigs were collected upon arrival (–8) and on –7, 0, 7, 14, 21, 24, 28, 32, 35 and 42 days postinfection. Blood samples were collected from all pigs on –7, 0, 4, 7, 11, 14, 21, 28, 35, and 42 dpi. Fecal samples were collected from all 20 pigs on –7 and 0 dpi.

In addition to these planned sample collection times, blood, feces and weights were collected on the day of death or euthanasia. Pigs were humanely euthanized under the direction of the attending laboratory animal veterinarian if (1) pigs had greater than or equal to 20% weight loss; (2) pigs were moribund or nonresponsive to veterinary treatment; or (3) pigs had severe dyspnea or clinical disease that compromised animal welfare. At 42 dpi, all remaining pigs were humanely euthanized, and complete necropsies were performed.

This study provides evidence of the significant relationship between the gut microbiome and outcome following systemic viral infections in swine. Most importantly, novel insight is provided into our ability to modulate the microbiome via FMT to improve the clinical outcome of pigs to common pathogens. Future research is needed to understand the mechanism of this relationship and how large-scale microbiome modulation could be adapted to increase the health of PRRS-virus-positive herds in the field.

Effective against PRRS virus
FMT is a potential alternative disease control method, where pigs with diverse and beneficial gut microbiota have fewer health challenges, including those predisposed by PRRS virus infections. Furthermore, FMT may be an alternative to antimicrobials in swine production through improving nutrient digestion and immune response during respiratory infections.

Additionally, FMT reduced morbidity, mortality and virus replication through an enhanced immune response, as indicated by increased antibody production. FMT is a novel disease control tool to improve the health and welfare of swine with respiratory infections. Overall, fecal transplantation from high-health sows within the herd is likely an underused, widely available and inexpensive tool for improving the health and response to disease in pigs.

This research was originally published in the journal Frontiers in Microbiology on July 23, 2018, doi: 10.3389/fmicb.2018.01631.

For further information, contact Megan Niederwerder.

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