Species- or genus-dependent immunostimulatory effects of gut-derived potential probiotics.

The immune regulatory effects of probiotics have been widely recognized to be strain-specific. However, it is unknown if there is a species- or genus-dependent manner. In this study, we use an in vitro mesenteric lymph node (MLN) model to systematically evaluate the immunostimulatory effects of gut-derived potential probiotics. The results exhibit an obvious species or genus consensus immune response pattern. RNA-seq shows that T cell-dependent B cell activation and antibody responses may be inherent to this model. Of the five tested genera, Akkermansia spp. and Clostridium butyrium directly activate the immune response in vitro, as indicated by the secretion of interleukin-10. Bifidobacterium spp. and Bacteroides spp. activate immune response with the help of stimuli (anti-CD3 and anti-CD28 antibodies). Lactobacillus spp. blunt the immune response with or without stimuli. Further investigations show that the cell surface protein of A. muciniphila AH39, which may serve as a T cell receptor cognate antigen, might evoke an in vitro immune activation. In vivo, oral administration of A. muciniphila AH39 influences the proportion of T regulatory cells (Tregs) in MLNs and the spleen under homeostasis in both specific pathogen-free and germ-free mice. All these findings indicate the distinct effects of different genera or species of potential gut-derived probiotics on intestinal and systemic immunity.