Immunologic effects of probiotics against respiratory viral infections
PhD student: Katrine Damgaard Winther
THE PROJECT
Probiotics are live microorganisms that may confer health benefits to the host and are used as dietary supplements for both humans and animals. Being a dietary supplement administered orally, probiotics have been thought to exert their effects by interacting with the intestinal barrier, the immune cells of the intestine or the microbiota, but increasing amount of research suggest that probiotics may elicit functions beyond the intestine e.g., in the lungs during respiratory infections (i.e. the ‘Gut-lung axis’). Several clinical and animal studies indicate that probiotics can reduce the risk or duration of respiratory tract infections (RTI) and that some probiotics have antiviral effects; however, the antiviral properties of probiotics are unclear. Several modes of actions have been proposed, including modulation of the immune system, and thereby promoting systemic immune responses and/or enhancing cellular immunity. Probiotics are thought to modulate the activity of immune cells, which can then enter circulation and modulate the immune response in the lungs during a respiratory challenge.
PURPOSE
The overall aim of this thesis was to investigate if and how specific probiotic strains can modulate responses in immune cells, and whether they will have beneficial effects against respiratory viruses through stimulation of local and/or systemic immune responses when administered in vivo to mice and pigs.
The primary objectives were as follows:
- Screening of probiotic candidate strains in relevant in vitro assays
- In vivo challenge trial with two candidate strains against Influenza A in mice
- In vivo challenge trial with a probiotic strain against Influenza A in pigs
RESULTS
In summary, the PhD project investigated the immunomodulatory properties of 14 probiotic strains. The results revealed that most strains displayed a synergistic effect when co-incubated with poly(I:C) (which mimics a viral response), leading to increased secretion of IL-6 and TNF-α from a macrophage cell line. Importantly, this synergistic effect was found to be independent of TLR-2. Notably, only strains belonging to the Bacillus genus were able to induce this effect in alveolar macrophages (AMs). In conclusion, our findings demonstrate that probiotic bacterial strains possess strain-dependent immunomodulatory properties revealing strain-dependent effects.
Based on the screening study, two probiotic strains, Enterococcus faecium-669 and Bacillus subtilis-597, were assessed for their impact on the outcome of infection in mice challenged with influenza A. The first study showed reduced mortality and lower viral loads while the second study showed a reduction in viral load in the B. subtilis-597 group compared to the positive control group. However, this reduction in viral load did not result in reduced mortality.
Further studies with Bacillus subtilis-597 in pigs hinted at a potential to possibly mitigate lung damage during swine influenza infection, with observed anti-inflammatory effects independent of the gastrointestinal microbiota. However, further studies with larger cohorts of animals will be needed to substantiate this. These findings underscore the potential of specific probiotic strains, notably Bacillus subtilis-597, to modulate host immune responses and alleviate the severity of respiratory viral infections.
winther.katrine@gmail.com