Dr. Sebastiano Busato, Associate Research Scientist at United Animal Health, Samanta Fensterseifer, DVM, MS, Staff Research Scientist at United Animal Health, and Beth Galbraith, MS, Research Manager at Microbial Discovery Group
Viral outbreaks in the livestock industry can be particularly challenging to control. In the case of diseases for which no vaccination protocol exists, producers must rely on supportive care, increased biosecurity measures and, in extreme cases, culling of infected animals to mitigate infection spread. While viral infection alone can impact animal health and performance, host immune factors as well as secondary challenges with suppressed feed and water intakes, increased inflammation and exposure to opportunistic secondary pathogens can compound disease severity (Figure 1).
As strategies are developed to manage viral infections, understanding the interplay of pathogens in coinfection disease syndromes can further assist in developing management approaches. Preventative measures can go hand in hand with dietary intervention, and new research supports the role of probiotics in reducing disease incidence and progression in livestock.
MULTIPLE PATHOGENS CREATE COMPLEX DISEASE SYNDROMES
Through United Animal Health’s PathKinex™ microbial surveillance platform, insights into pathogen synergies in animals exhibiting clinical disease can become clearer (Figure 2).
Meta-analyses revealed that 58% of cows exhibiting clinical enteric disease harbored more than one pathogen, a state known as coinfection. While severity of disease is influenced by multiple pathogens, PathKinex data also showed that disease incidence is strongly correlated with the presence of multiple pathogens (Figure 3). For example, cows testing positive for both pathogenic E. coli and Salmonella had a ~54% higher likelihood of presenting clinical symptoms, compared with animals only infected with E. coli.
Further, coinfection can happen across domains of life: not only multiple bacterial pathogens, but also bacteria and fungi, or bacteria and viruses. In the case of avian influenza virus, studies in poultry have demonstrated that co-infection with other viral or bacterial pathogens can impact viral shedding, viral replication, and clinical outcomes [1].
Managing disease complexes associated with multiple pathogens requires a multi-pronged approach, including interventions that aid in disrupting pathogenic synergies. Considerations includes tools that protect gut integrity, promote innate immunity, and reduce pathogen presence and quantities contributing to the clinical picture.
PROBIOTICS AND VIRAL INFECTIONS: AN UNLIKELY COMBINATION?
Initial research on probiotics (also known as DFMs – direct-fed microbials) focused primarily on production performance and control of bacterial pathogens. It is well established that DFMs can lead to greater milk yield and increase in milk components, as well as inhibition of pathogens such as Streptococcus and Salmonella [2]. The latter can be achieved by direct interaction between the probiotics and the pathogen, such as through the production of antimicrobial compounds and the competition for nutrients and adhesion sites in the gut mucosa. However, DFMs can also combat pathogens indirectly: by improving gut barrier function, reducing intestinal permeability, and stimulating the immune response in the host [2]. All of these functions would allow probiotics to exert a protective role against multiple pathogenic taxa, including viruses. Fittingly, a 2021 meta-review highlighted a positive effect of probiotics against multiple respiratory and digestive viruses, including influenza (H1N1, H3N2), RSV, PIV 1-2, rotavirus and norovirus in mouse, human and in vitro studies [3].
Recent research from United Animal Health, in collaboration with Dr. Federico Zuckermann at University of Illinois, supports this theory [4]. In a 2022 study published in Infection and Immunity, weanling pigs were subjected to infection with either a bacterial challenge (Salmonella enterica serotype Cholerasuis), a viral challenge (Porcine reproductive and respiratory syndrome virus – PRRSV), or both (Figure 4).
Half of the pigs in each group were also receiving ProVent ECL, a direct-fed microbial containing six strains of Bacillus subtilis, throughout the duration of the trial. While the dually challenged animals had poorer health and production outcomes than either the unchallenged or single-challenged animals, pigs receiving ProVent ECL showed a marked reduction in lung lesions, and a 10-fold lower viral load in the lung, compared to animals not receiving the DFM (Figure 5). Furthermore, animal fed ProVent ECL were less likely to display Salmonella colonization in the lung, indicating a protective role against both pathogens in the study – bacterial and viral (Figure 6).
While the nature of this effect is not completely clear, the authors argue that the DFM had a modulatory effect on the immune response, which was also measured in the study. Data supports this theory, as pigs receiving ProVent ECL had increased expression of the cytokines IL-1 and IL-8 (Figures 7 & 8), as well as the receptors NOD-2 and TREM-1, which suggest that the DFM had a systemic effect on the immune system.
PROBIOTICS AS A TOOL AGAINST COINFECTION
Promoting resilience in the face of stacked stressors is critical to protecting health and maximizing genetic potential. While there are no silver bullets, using multiple interventions that decouple pathogenic synergies through lowering pathogen load, increasing innate immunity and promote gut integrity may lead to greatest successes. This can include tools such as effective Bacillus-based solutions. To learn more on coinfections, pathogen surveillance and United Animal Health’s Bacillus-based solutions, visit UnitedAnH.com/Strateris or talk to a United Animal Health account manager today.
REFERENCES
[1] A. Samy and M.M. Naguib, “Avian Respiratory Coinfection and Impact on Avian Influenza Pathogenicity in Domestic Poultry: Field and Experimental Findings,” Vet Sci. vol. 5, no.1, p. 23, Feb 2018, doi: 10.3390/vetsci5010023.
[2] Y. Ban and L. L. Guan, “Implication and challenges of direct-fed microbial supplementation to improve ruminant production and health,” Journal of Animal Science and Biotechnology, vol. 12, no. 1, p. 109, Oct. 2021, doi: 10.1186/s40104-021-00630-x.
[3] A. Lopez-Santamarina et al., “Probiotic Effects against Virus Infections: New Weapons for an Old War,” Foods, vol. 10, no. 1, Art. no. 1, Jan. 2021, doi: 10.3390/foods10010130.
[4] F. A. Zuckermann et al., “Bacillus-Based Direct-Fed Microbial Reduces the Pathogenic Synergy of a Coinfection with Salmonella enterica Serovar Choleraesuis and Porcine Reproductive and Respiratory Syndrome Virus,” Infection and Immunity, vol. 90, no. 4, pp. e00574-21, Mar. 2022, doi: 10.1128/iai.00574-21.
