Many food factors such as probiotics are effective against human gastrointestinal disorders including inflammatory bowel disease. However, it remains unclear how probiotics act to protect against intestinal inflammation. Here, we describe a novel in vitro gut inflammation model for evaluating the anti-inflammatory activity of food factors, and in vitro and in vivo inflammation models for assessment of the gut anti-inflammatory activities of Lactococcus lactis subsp. cremoris FC (strain FC). A coculture system with intestinal epithelial Caco-2 cells and RAW264.7 macrophages can be used to assess the anti-inflammatory activity of food factors. Stimulation of RAW264.7 cells with lipopolysaccharide (LPS) increases tumor necrosis factor (TNF)-α production from RAW264.7 cells and interleukin (IL)-8 mRNA expression in Caco-2 cells and decreases the transepithelial electrical resistance of Caco-2 monolayers. The increases in TNF-α and IL-8 mRNA are suppressed by anti-TNF-α antibodies or budesonide. This indicates that this coculture model can imitate gut inflammation in vivo. Strain FC significantly downregulates IL-8 mRNA expression in Caco-2 cells and inhibits nuclear factor-κB nuclear translocation in RAW264.7 cells. A mouse model of dextran sulfate sodium (DSS)-induced colitis has been used to assess the anti-inflammatory activity of strain FC, which significantly ameliorates shortening of the colon and improves colon histology, especially in inflammatory cell infiltration, and proinflammatory cytokine and chemokine mRNA expression in inflamed tissue. These results indicate that oral administration of strain FC improves DSS-induced colitis through inhibition of inflammatory cell infiltration and that Caco-2/RAW264.7 cells stimulated with LPS can be used for screening anti-inflammatory factors and elucidating the mechanism of anti-inflammatory activity.

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The gut-brain axis has been described as a bi-directional neuro-humeral communication system and is implicated in the pathogenesis of functional gastrointestinal disorders such as irritable bowel syndrome (IBS). Recent work has shown that a subset of patients with IBS show evidence of low grade immune activation and inflammation in the colonic mucosa. This review focuses on the role of the intestinal microbiota and discusses the interrelationship between the intestinal microbiota and maintaining of low grade inflammation, gut dysfunction or behavioral changes using murine models and clinical studies. The findings in murine models show that perturbation of gut flora is a putative mechanism for gut dysfunction in IBS and together with clinical studies they indicate that dysbiosis in patients with IBS psychiatric co-morbidity.

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Equol, a bacterial product from daidzein, has been shown to provide beneficial effects. The impact of polydextrose, a compound known to affect the intestinal flora, was studied for its impact on mouse intestinal flora and isoflavonoids in the cecum and plasma. We hypothesized that polydextrose would change the metabolism of isoflavonoids and intestinal flora in mice. Male mice were administered a 1% polydextrose solution (PD) in their drinking water which was provided ad libitum, and were compared with a control group (CO, water only). Both groups were fed the AIN-93M diet for 24 days. Plasma equol and cecal equol concentrations and in vitro equol production from daidzein with fecal flora of mice were measured. The plasma equol concentration was significantly higher in the PD group than in the CO group at 22 hr after the administration of daidzin. The concentration of equol in the cecum was significantly greater in the PD group than in the CO group at 22 hr after administration of daidzin. In the in vitro incubation of daidzein with the fecal flora of mice, equol concentrations were greater in the PD group. These results suggest that dietary polydextrose has the potential to affect equol production by altering the metabolic activity of the intestinal flora and/or the gut environment.

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