**Author details**

276 Lactic Acid Bacteria – R & D for Food, Health and Livestock Purposes

**6. Conclusion** 

IgA ASC responses probably play a more important role in rotavirus protective immunity than the IFN-γ producing CD8+ T cell responses (Yuan et al., 1996; Yuan et al., 2008), the effect of LA on virus-specific ASC responses also need to be taken into consideration regarding the differences in the protection conferred by the AttHRV vaccine with high or low dose LA. Although the low dose LA enhanced IFN-γ producing CD8+ T cell responses, it had negative effects on the serum antibody and ASC responses induced by the AttHRV vaccine. To improve the AttHRV vaccine efficacy, a different dose of LA (possible an intermediate dose) or a different probiotic strain (i.e. LGG) may be optimal to promote a

Differential modulating effects on innate and adaptive immune responses by low dose versus high dose of the same LA NCFM strain were clearly demonstrated in gnotobiotic pigs. Low dose LA significantly enhanced the Th1 type effector T cell responses and decreased Treg cell functions in AttHRV-vaccinated pigs. Meanwhile, low dose LA resulted in a suppressed Th2 response, as evidenced by significantly reduced virus-specific ASC responses and serum antibody titers compared to the AttHRV only group. The dose effects of LA on IFN-γ producing T cell and CD4+CD25-FoxP3+ Treg cell immune responses were similar between the intestinal and systemic lymphoid tissues. Thus the same probiotic strain used in different doses can either increase or reduce mucosal and systemic immune responses induced by vaccines. These findings have significant implications in the use of probiotic lactobacilli as immunostimulatory versus immunoregulatory agents. Probiotic products are increasingly used to improve health, alleviate disease symptoms, and enhance vaccine efficacy. Our findings suggest that probiotics can be ineffective or even detrimental if not used at the optimal dosage for the appropriate purposes, highlighting the importance

The gnotobiotic pig model is a valuable animal model for study of probiotic-virus-host interaction because of the many similarities between human and porcine intestinal physiology and mucosal immune system (Meurens et al., 2012). The gnotobiotic status prevents confounding factors from commensal microflora that are present in conventionally reared animals or in humans. Unlike gnotobiotic mice, gnotobiotic pigs are devoid of maternal antibodies, thus providing an immunologically naïve background that allows clear identification of the immune responses to a single vaccine in hosts colonized with a qualitatively and quantitatively defined probiotic bacterial strain (Butler, 2009; Yuan & Saif, 2002). Although data from studies of gnotobiotic animal models may not be generalized directly to normal animals or humans, gnotobiotic animals provide a medium in which investigating the complex interrelationships of the host and its associated microbes become possible (Coates, 1975). Our findings provide a good starting point for identification of the optimal dosage of a probiotic strain. But nonetheless, the optimal dosage needs to be confirmed in conventionalized gnotobiotic pigs and in human clinical trials in order to

balanced Th1 and Th2 response without increasing Treg cell responses.

of not only strain but also dose selection in probiotic studies.

achieve the appropriate adjuvant effect for rotavirus and other vaccines.

Lijuan Yuan, Ke Wen, Fangning Liu and Guohua Li *Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University, USA* 
