Immunomodulation has been shown to be one of the major functions of probiotic bacteria. This review is presented to provide detailed information on the immunomodulatory properties of probiotics in various animal models and clinical practices. Probiotics can regulate helper T (Th) responses and release of cytokines in a strain-specific manner. For example, Lactobacillus rhamnosus GG can induce beneficial Th1 immunomodulatory effect in infants with cow's milk allergy and relieve intestinal inflammation in atopic children by promoting IL-10 generation. Mechanism of action of probiotics on antigen-presenting cells at gastrointestinal tract is also postulated in this review. Probiotic bacterial cells and their soluble factors may activate dendritic cells, macrophages, and to certain extent monocytes via toll-like-receptor recognition and may further provoke specific Th responses. They are speculated to elicit immunomodulatory effects on intestinal and systemic immunities.

Lactobacillus rhamnosus GG (LGG) cells have been shown to promote type-1 immune responsiveness; however knowledge of immunomodulation of soluble factors secreted by LGG is limited. This is the first study to investigate whether LGG soluble factors promote a comparable immune responsiveness as the bacterial cells. Both treatments − LGG conditioned medium with (CM + LGG) or without (CM)LGG cells, in this study increased expression of several toll-like receptors (TLRs) in all studied cell types and antigen presentation-associated receptor HLA-DR in macrophages and "intermediate" monocytes; but decreased that of activation markers on monocytes and macrophages and production of IL-10, IL-12 and TNFα in macrophages. In co-culture with mononuclear cells, CM increased Th1-type cytokine profile but not as pronounced as CM + LGG. This study suggests that LGG soluble factors exert similar immunomodulatory effects as the intact cells, but cells may be required for optimal type-1 immune responsiveness polarizing capacity of this probiotic strain.Conditioned medium of lactobacilli, which is cell-free supernatant containing soluble factors, has been shown to enhance lactobacilli but inhibit invasive Escherichia coli, adhere to intestinal epithelial cells, intestine mucus and gastric mucin 1,2 ; and elicit antibacterial activity against pathogens such as Salmonella species 3-5 . Soluble factors refer to metabolites, proteins, DNA and cell-wall constituents 2,6 . Lactobacillus rhamnosus GG (LGG) (ATCC 53103) is perhaps the most researched lactobacilli in the world; but some of its soluble factors have only been recently identified, for example, p75 and p40 proteins 7 , porcine serpine protease inhibitor, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), cell wall-associated hydrolase, transcriptional regulator and phosphoglycerate kinase 8 . These factors play an important role in the physiology of LGG [8][9][10][11][12] and have been found beneficial to the gut, for example, diminishing apoptosis of intestinal epithelium 7,13 , enhancing intestinal crypt survival 13 and preserving cytoskeletal integrity of intestine 14 . However, knowledge of the immunomodulatory effects exerted by LGG soluble factors is lacking. Our previous study shows that LGG cells activate antigen-presenting cells (APCs) of healthy blood donors to promote type-1 immune responsiveness 15 . Herein, this study aimed to investigate whether LGG soluble factors promote the same immune responsiveness as the cells, and if LGG cells alter the immunomodulatory properties of the soluble factors. Elucidating the immunomodulatory effects of LGG soluble factors will help to draw evidence-based guidelines of this strain for the treatment development for various diseases such as drug synthesis and vaccine development. ResultsTLR mRNA expression in DCs, macrophages and monocytes. TLR mRNA levels of DCs, macrophages and monocytes are shown in Fig. 1. They were detected after 24-hour incubation with CM or CM + LGG. Both CM and CM + LGG increased TLRs 1, 4, 5, 6, 7, 8 and 9 m...

This probiotic intervention targeting microbiota may be used in conjugation with other dietary supplements or drugs as part of prevention strategies for early-stage colon cancer, after further clinical validations in human.