Co-culture systems of lactic acid bacteria and yeasts for bioproduction are described with two typical examples. A novel control method exploiting microbial interaction in the co-culture system is introduced as the first example. In order to control pH in an antimicrobial peptide (nisin) production process by Lactococcus lactis subsp. lactis (ATCC 11454), microbial interaction between L-lactate production by L. lactis and its assimilation by Kluyveromyces marxianus was utilized. A cascade pH controller coupled with DO control was newly developed and the specific lactate consumption rate of K. marxianus was controlled by changing the dissolved oxygen (DO) concentration. pH and lactate were kept at constant levels and nisin accumulated in medium to high levels, compared with other pH control strategies, such as processes without pH control and with pH control by addition of alkali. The second example is polysaccharide kefiran production by co-culture of Lactobacillus kefiranofaciens and Saccharomyces cerevisiae. Productivity of kefiran was increased in the co-culture system of S. cerevisiae under an aerobic condition. Not only the effect of removal of lactic acid but also the additional effect of S. cerevisiae are discussed through the simulation of the system.

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Many works on the biological functions of dairy lactic acid bacteria (LAB) have contributed to the application of LAB in functional foods and supplements in the global market. More recently, the new term “immunobiotics”, has been proposed to identify probiotic bacteria that promote health through activation of intestinal immunity from those with strictly local immunity, and expected for an appropriate evolutionary development. We have studied specific effector molecules and their receptor targets. Recently, we found that immunostimulatory AT oligonucleotide (AT-ODN), but not CpG ODN, from Lactobacillus gasseri JCM 1131^T triggered. immune responses via Toll-like receptor 9 (TLR9), which has been identified as a particular receptor for bacterial DNA containing the specific sequence pattern of unmethylated CpG dinucleotide. Through the discovery of TLR9, possible molecular mechanisms in immune responses through bacterial DNA have been rapidly revealed in mice. Recently, we found that ATODN from Lactobacillus gasseri, possibly induces immunoactivation in Peyer's patches (Pps)via TLR9. We demonstrated that TLR9 is a receptor for not only CpG but also for non-CpG AT ODN as a result of the induction of nuclear factor-κB (NF-κB) activation by gene reporter assay. This review describes our recent study on the immunostimulatory activity of LAB via TLRs, especially TLR 9 and 2 and discuss future trends in the development of “Immunobiotic Foods” through intestinal immunoregulation mediated by “Immunobiotic” LAB via TLRs.

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