To accommodate the vast antigenic exposure from both food components and commensal bacteria, the gut has evolved a naturally anti-inflammatory environment. We have recently shown that lactic acid bacteria (LAB), a major population of small intestinal microbiota and often found in fermented foods, contain a large amount of double-stranded RNA and capable of inducing interferon-β (IFN-β) production from dendritic cells (DCs) via the Toll-like receptor 3 (TLR3) pathway. It is a significant feature of LAB and was not observed in other bacteria tested. Moreover, IFN-β secreted in response to LAB prevented experimental colitis. These results identify TLR3 as a sensor to small intestinal commensal bacteria and contribute to anti-inflammatory mechanism. We also show that oral administration of β-glucan enhance intestinal and systemic immune response in dectin-1-dependent manner. Thus elucidation of "gut to systemic immune-homeostasis" mediated by innate signals will be valued for the development of gut-biology and science-based food immunology, with a focus on innovation in the health and medical industries.