Several studies on the pathogenesis of allergy both in man and experimental animals continue to show the importance of commensal bacteria in the gastrointestinal tract in stimulating and directing the immune system. The interest in modulating commensal bacteria flora with pre- and probiotics to prevent and treat food allergy has multiplied in recent years. We recently studied 230 infants with atopic dermatitis and suspected cow’s milk allergy. The infants were randomly allocated to groups which received Lactobacillus GG (LGG), a mixture of four probiotic strains (MIX) or placebo for 4 weeks. We inferred that probiotics induce systemically detectable low-grade inflammation, which may explain the clinical effects and the secretion pattern of cytokines induced by PBMC. To study the ability of probiotics to prevent allergy in children, we recruited 1223 pregnant women carrying fetuses at increased risk of allergy for a double-blind placebo-controlled trial. Mothers used a mixture of four probiotic bacteria or a placebo from the 36th week of gestation. Their infants received the same probiotics plus prebiotic galacto-oligosaccharides for 6 months. At the 2-year follow-up, a total of 925 infants participated. The cumulative incidence of allergic disease did not differ significantly between the synbiotic and the placebo group. However, synbiotics significantly reduced eczema. The preventive effect of synbiotics was more pronounced against IgE-associated diseases. At the 5 year follow-up, 891(88%) of the 1018 intention-to-treat infants attended. In the probiotic and placebo groups, frequencies of allergic symptoms and IgE-associated allergic disease and sensitization were similar, and the frequencies of eczema did not differ between the groups. Atopic eczema, allergic rhinitis and asthma appeared equal frequency in the groups. However, less IgE-associated allergic disease occurred in the cesarean-delivered infants given probiotics. In cesarean-delivered childen, we noticed a delayed rise in bifidobacteria recovery in placebo-treated children which was corrected by pro- and prebiotic supplementation. Indications from studies of feces and blood at the age 6 months suggest that probiotics may enhance both inflammation and immune defence of the gut. The probiotic treatment further stimulated maturation of the immune system since the infants given probiotics showed increased resistance to respiratory infections and improved vaccine antibody responses.
In vitro M cell models, consisting of co-cultures of Caco-2 cells and lymphoid cells, were developed and examined to observe bacterial transport. However, under our experimental conditions, the differentiation of Caco-2 cells into M cell-like cells could not be induced efficiently. To obtain a functionally stable M cell model based on human cells, C2BBe1 cells were screened and co-cultured with human Raji cells. In our co-cultures, increased sialyl Lewis A antigen expression and decreased Ulex europeaus agglutinin 1 binding were observed. Regarding the functional properties of the model, microsphere and lactic acid bacteria transport across the C2BBe1 co-cultures were increased compared with the levels seen in monocultures. The C2BBe1 monolayers that were co-cultured with Raji cells exhibited some M cell features; therefore, we consider our M cell model to be useful for investigating the interactions of bacteria with M cells.
Several fold increase in allergic diseases in developed, high-income countries during recent decades is attributed to environmental changes such as urbanization with improved hygiene. This, together with conquering severe bacterial infections during childhood, has reduced the microbial stimulation of the developing immune system of infants. Studies on the pathogenesis of allergy both in man and experimental animal have shown the importance of commensal bacteria in the gastrointestinal tract in stimulating and directing the immune system. The interest in modulating commensal bacterial flora with probiotics to prevent and treat allergy has multiplied in recent years.In the present review we report results on randomized, controlled studies in which childhood atopic eczema was treated or which aimed to prevent development of allergy during childhood.Nine studies with 639 patients have looked at the effect of probiotics in treatment of eczema. While 3 studied showed no effect, other studies suggested a moderate benefit of the use of probiotics on the severity of eczema. Studies suggested that the effect may be seen particularly in patients with food allergy and/or sensitization.Nine studies have reported on the prevention of allergy on 6 study population with altogether 1989 high risk infants. While the early study reporting the development of allergy at ages 2, 4 and 7 years showed a marked reduction of eczema in 77 treated infants, later studies have failed to show similar success. Two studies showed no effect. In the largest study with more than 900 children at age 2 atopic eczema was reduced by 20%, but at age 5 positive effect was present in only the subgroup of children who had born by cesarean section. None of studies has reported adverse effects of probiotics in infants.Result in both treatment and prevention studies are quite variable, the major reason being the use of different strains of probiotic bacteria and varying types of intervention. Even if the results are encouraging, we need a stronger effect. This may be reached by finding new strains of probiotics affecting stronger stimulation of immune system, together with longer lasting and varying treatment schedules. However, safety issues have to be observed.
Environmental factors during early infancy could theoretically affect immune system development and subsequent risk of allergic disease. One potentially helpful exposure is early infant supplementation with specific probiotic strains. Unlike other exposures, probiotic supplementation is feasible and has a good safety profile. A review of recent randomized, controlled trials suggests that the effect of supplementation with probiotics on preventing the development of allergic disease is mixed. Further studies are needed to define potential mechanisms of action, such as effects on infant microbiota, as well as potential subgroups of patients that may benefit from these interventions.
Isoflavones contained in the root and flower of Kudzu (Pueraria lobata and related species) are suggested to be the critical component for its effects. Although metabolism of soy isoflavones has been well studied, the composition of isoflavones found in Kudzu is completely different from that of soy isoflavones. In the present study, we investigated whether isoflavones found in the flower of Pueraria thomsonii, a species of Kudzu, were metabolized by human fecal microbiota and murine small intestinal enzymes. Among 5 glycosidic isoflavones of the Pueraria thomsonii flower, tectorigenin 7-O-xylosylglucoside, tectoridin, genistin and glycitin were completely hydrolyzed by a homogenate of germfree mouse small intestine without contribution of bacteria. Released aglycones were not further metabolized, except that up to half of glycitein disappeared. Mouse small intestinal enzymes did not metabolize 6-hydroxygenistein 6,7-di-O-glucoside. Isoflavone aglycones as well as 6-hydroxygenistein 6,7-di-O-glucoside were highly metabolized by most of the human fecal suspensions. Metabolites were not detected with the present analytical methods in most cases. Although further investigations of the pharmacokinetics of Pueraria thomsonii flower isoflavones are needed, the results of the present study indicate active metabolism of Pueraria thomsonii flower isoflavones in the human intestine.
Lactobacillus pentosus (L. pentosus) strain S-PT84, isolated from Kyoto pickles, enhances splenic natural killer (NK) cell activity, and has high T-helper1 (Th1) cytokine and type 1-IFN (IFN-α) inducing activity. In the present study, we investigated the influence of S-PT84 ingestion on the mucosal immunity of healthy and Salmonella Typhimurium (S. Typhimurium)-infected mice. In the S. Typhimurium infection model, numbers of S. Typhimurium in feces and the spleen were significantly decreased, and body weight loss and deterioration in the general health score of S. Typhimurium-infected mice were improved by S-PT84 ingestion. Oral administration of S-PT84 enhanced IL-5 and IL-6 production from Peyer's patch cells in vitro, with a concomitant significant increase in IgA production from Peyer's patch cells, which may explain the mechanism of enhanced IgA production in the small intestine in vivo. These results suggest that S-PT84 ingestion is useful for the maintenance of health or the improvement of certain symptoms during pathogen infection.
Western medicine has only recently discovered that the intestinal microbiota is a major determinant of the well-being of the host. Although it would be oversimplifying to limit the benefits of breastfeeding compared to cow milk based infant formula to differences in gastrointestinal flora, the impact of the latter has been demonstrated beyond doubt. As a consequence, gastro intestinal flora manipulation with pre- and probiotics added to infant formula or food (mainly milk based products) and/or with food supplements have become a priority area of high quality research. The composition of intestinal microbiota can be manipulated with "biotics": antibiotics, prebiotics and probiotics. Commercialised pre- and probiotic products differ in composition and dose. Major threats to the concept of developing a major role for intestinal microbiota manipulation on health are the commercialisation of products claiming health benefits that have not been validated. Legislation of food supplements and medication differs substantially and allows commercialisation of poor quality food supplements, what will result in negative experiences. Medicinal products can only be advertised for which there is scientific proof of benefit that has been demonstrated with "the same product with the same dose in the same indication". Specificity of prebiotics and probiotics strains and product specificity are of importance, although high quality evidence for this assertion is missing. Dose-efficacy studies are urgently needed. Probiotics are "generally regarded as safe", but side effects such as septicemia and fungemia have sometimes been reported in high-risk situations.
Many Lactobacillus and Lactococcus strains are generally regarded as safe for consumption because they are utilized for food fermentation or inhabit the intestinal mucosa as commensals. Recently, vaccine delivery systems using lactic acid bacteria (LAB) have been under development. Our research group has been investigating the development of oral mucosal vaccines against Salmonella enterica serovar Enteritidis (SE) using Lactobacillus casei IGM393 as an antigen delivery vehicle. Recombinant lactobacilli expressing SE antigens, FliC, SipC, and OmpC, have been constructed and orally administered to mice. Antigen specific immune responses and protective immunity were elicited after the immunization. For adjuvant-delivery, IL-1β-secreting L. casei was also engineered and its effects evaluated in vitro and in vivo. This article reviews a novel approach to the elimination of Salmonella via the development of a vaccine in lactobacilli.
Autonomic nerves, consisting of both sympathetic and parasympathetic nerves, regulate various bodily functions such as blood pressure, body temperature, glucose metabolism, energy metabolism, and digestion. Our studies in rats and mice have demonstrated that food, flavor, and music affect physiological phenomena via changes in autonomic neurotransmissions. Intestinal injection of Lactobacillus johnsonii La1 (NCC533) suppressed sympathetic nerves that innervate the adrenal gland and kidney of urethane-anesthetized rats, lowering blood glucose and blood pressure levels, and excited the gastric parasympathetic nerve, elevating appetite and body weight. In contrast, intestinal injection of Lactobacillus paracasei ST11 (NCC2461) excited sympathetic nerves that innervate white and brown fat and the adrenal gland, increasing lipolysis and body temperature, and suppressed the gastric parasympathetic nerve, reducing appetite and body weight. Interestingly, we found that the hypothalamic suprachiasmatic nucleus (SCN), a master circadian clock, and histamine receptors in histaminergic neurons play important roles in peripheral autonomic control. To investigate the possible role of SCN and histamine receptors in lactobacilli-mediated pathology, we created an SCN-lesion model and experimented with histaminergic blocker injections. SCN lesion or injection of thioperamide, a histamine H3-receptor antagonist, eliminated the suppression of renal sympathetic nerve activity by NCC533, preventing blood pressure decline, and inhibited the enhancement of the gastric parasympathetic nerve induced by NCC533. In addition, diphenhydramine, a histamine H1-receptor antagonist, abolished the increases in renal sympathetic nerve activity and blood pressure caused by NCC2461. Infradiaphragmatic vagotomy eliminated the suppression of renal sympathetic nerve activity by NCC533, but did not affect the excitation of the renal sympathetic nerve by NCC2461. Collectively, these findings strongly suggest that SCN and histamine neurons are involved in the lactobacilli-mediated pathology of autonomic nerves and related physiological changes through abdominal afferent vagal pathway input to the central nervous system.
Much attention has been focused on the biological effects of equol, a metabolite of daidzein produced by intestinal microbiota. However, little is known about the role of isoflavone metabolizing bacteria in the intestinal microbiota. Recently, we isolated a dihydrodaidzein (DHD)-producing Clostridium-like bacterium, strain TM-40, from human feces. We investigated the effects of strain TM-40 on in vitro daidzein metabolism by human fecal microbiota from a male equol producer and two male equol non-producers. In the fecal suspension from the male equol non-producer and DHD producer, DHD was detected in the in vitro fecal incubation of daidzein after addition of TM-40. The DHD concentration increased as the concentration of strain TM-40 increased. In the fecal suspension from the equol producer, the fecal equol production was increased by the addition of strain TM-40. The occupation ratios of Bifidobacterium and Lactobacillales were higher in the equol non-producers than in the equol producer. Adding isoflavone-metabolizing bacteria to the fecal microbiota should facilitate the estimation of the metabolism of isoflavonoids by fecal microbiota. Studies on the interactions among equol-producing microbiota and DHD-producing bacteria might lead to clarification of some of the mechanisms regulating the production of equol by fecal microbiota.
To evaluate the effect of Lactobacillus plantarum strain Hokkaido, which was isolated from a kind of Japanese pickle, on the incidence of diarrhea in calves and on the intestinal microflora, we performed feeding tests with a milk replacer containing Lactobacillus sp. In Experiment 1, thirty two male Holstein calves were divided into two groups, a control (C) group and LPH group. L. plantarum strain HOKKAIDO was orally administered to the LPH group for 35 days. The diarrhea score and the number of calves with watery or soft stool were significantly (p<0.05) smaller in the LPH group than in the C group. In Experiment 2, ten male Holstein calves were divided into three groups: a control group, LPH group and BOV group. BovactinTM was administered to the BOV group and the experimental protocol followed that of Experiment 1. No significant difference was observed in the incidence of diarrhea among the three test groups. However, when the data of Experiments 1 and 2 were pooled, the incidence of diarrhea in the LPH group was significantly (p<0.05) lower than that of the control group. These results indicate that L. plantarum strain Hokkaido reduces the incidence of diarrhea in calves. Analysis of the microflora and measurement of the stool type of the fecal samples that were collected 0, 15 and 28 days after the start of administration were performed using a T-RFLP method and visual analysis, respectively. The clustering of the T-RFLP profiles indicated that when the significance of the distributions of the samples among the clusters was tested, a significant difference (p<0.01) was observed only among the sampling-date groups. The average value of the pairwise Pearson r within each sampling-date group indicated that T-RFLP profiles varied considerably among the calves on day 0 and day 15, while the profiles of day 28 closely resembled each other. From these results, we infer that the intestinal microflora of calves are less settled in the early days of life, and this might partially explain the higher incidence of diarrhea in this period. Bacteria belonging to the class Clostridia were most predominant at all the sampling-date groups. The day 0 samples were characterized by a larger population of bifidobacteria and lactic acid bacteria (LAB). The day 15 samples were characterized by larger populations of LAB and the class Bacteroidia. The day 28 samples were characterized by a larger population of Bacteroides.
Shiga toxin-producing Escherichia coli and Salmonella, causative bacteria of food poisoning (intestinal infectious disease) in humans, are still serious problems. Shiga toxin-producing E. coli O157:H7 (STEC) grows and produces Shiga toxin (Stx) in the intestine, and causes hemorrhagic enteritis. A typical etiologic agent of Salmonella food poisoning, Salmonella enterica serovar Typhimurium (S. Typhimurium), grows in the intestine and invades the body via the intestinal epithelium, causing inflammation. The importance of the prevention of STEC- and S. Typhimurium-induced food poisoning has been stressed because they frequently cause outbreaks, the course is rapid, and only a very small number of bacteria (101 to 103 CFU) is needed to induce a severe infection. Probiotics are defined as `Live microorganisms which when administered in adequate amounts confer a health benefit on the host'. Bifidobacteria, major constituents of the intestinal flora, are typical probiotics which are expected to help prevent intestinal infection. In this study, we investigated the anti-infectious activity of bifidobacteria against STEC and S. Typhimurium infections using a mouse intestinal infection model, and analyzed the infection-preventive mechanism. For STEC infection, a novel mouse fatal infection model was prepared by combining STEC infection at 5 × 10 3 CFU and Mitomycin C (MMC) treatment (for the induction of stx gene expression) in the late logarithmic phase of intestinal STEC growth. The anti-infectious activity of the orally administered probiotic Bifidobcterium breve strain Yakult (BbY) was investigated using this mouse intestinal STEC infection model. STEC-induced death was strongly inhibited in BbY-treated mice. Interestingly, STEC growth in the intestine was not inhibited, but stx gene expression and Stx production were strongly inhibited. In addition, the intestinal environment was improved in the BbY-treated mice through normalization of the intestinal level of acetic acid, a major organic acid in the intestine, and pH. When STEC was grown in vitro in a medium reproducing the acetic acid level and pH in the cecum, Stx production was completely inhibited, suggesting that the expression of this pathogenic factor was inhibited by BbY-induced improvement of the intestinal environment. In the mouse intestinal S. Typhimurium infection model, BbY inhibited the abnormal growth of S. Typhimurium and improved the intestinal environment, resulting in the inhibition of systemic S. Typhimurium infection. This study, using an experimental animal model, clarified the preventive effect of the probiotic BbY on food poisoning (intestinal infectious disease) caused by STEC and S. Typhimurium. Improvements of the intestinal environment, such as elevation of the acetic acid concentration and decrease in pH level, induced by intestinal BbY colonization, are suggested to be important defense mechanisms for the inhibition of pathogenic factors production induce by intestinal STEC and retardation of intestinal S. Typhimurium growth. These findings suggest the usefulness of probiotics as a novel preventive agent for human food poisoning (intestinal infectious disease).
The resident microbiota of the mammalian intestine influences diverse homeostatic functions of the gut, including regulation of cellular growth, restitution after injury, maintenance of barrier function, and modulation of immune responses. However, it is unknown how commensal prokaryotic organisms mechanistically influence eukaryotic signaling networks. We have shown that epithelia contacted by enteric commensal bacteria in vitro and in vivo rapidly generate reactive oxygen species (ROS), and distinct microbial taxa have markedly different potencies in stimulating this response. This physiologically generated ROS is known to participate in a variety of cellular signal pathways via the rapid and transient oxidative inactivation of a number of regulatory enzymes. We show that these oxidant sensitive enzymes include key control points in the proinflammatory NF-κB pathway and in the regulation of cytoskeletal dynamics. Accordingly, we show various commensal bacterial have the ability to suppress inflammatory signaling and stimulate cell motility both in cell culture and in animal models. These events are consistent with known effects of the microbiota and selected probiotics. Collectively, our studies outline a molecular mechanism that may account for aspects of microbial-host cross-talk in the intestine in normal physiology and during therapeutic intervention with probiotics.
Many bifidobacteria produce an endo-α-N-acetylgalactosaminidase that liberates the O-linked galactosyl β-1,3N-acetylgalactosamine (GNB) from intestinal mucin glycoproteins. The molecular cloning of the Bifidobacterium longum enzyme was completed using information in public databases. The enzyme constitutes a novel glycoside hydrolase (GH) family 101 member. The gene encoding a specific 1,2-α -L-fucosidase was cloned from B. bifidum. The recombinant enzyme specifically hydrolyzes the terminal α-1,2-fucosidic linkages of various oligosaccharides, including human milk oligosaccharides and blood group substances. Analysis of its primary structure revealed that this enzyme constitutes a novel GH family 95 member. We also solved the crystal structure of its catalytic domain. We assumed that these bifidobacterial enzymes are involved in the metabolism of oligosaccharides in mucin glycoproteins that are abundant in the intestine. Some bifidobacteria strains produce a lacto-N-biosidase that releases galactosyl β- 1,3N-acetylglucosamine (LNB) from human milk oligosaccharides, but the other enteric bacteria do not. This disaccharide is one of the building blocks in human milk oligosaccharides and is rarely found in other mammalian milks. The lacto-N-biosidase gene was cloned from B.bifidum and we hypothesized that this enzyme is crucially involved in the degradation of human milk oligosaccharides. The genes encoding sialidase and α-1,3/4-L-fucosidase were also cloned from B.bifidum. These enzymes release modified sialic acid and L-fucose from human milk oligosaccharides, respectively. A solute-binding protein of a putative ABC transporter specific for GNB and LNB was also discovered, and its gene was cloned from B.longum. We named it GNB/LNB-binding protein and crystallized it. Isothermal titration calorimetry measurements revealed that this protein specifically binds GNB and LNB. We speculate that bifidobacteria have a novel GNB/LNB metabolic pathway.
It has become clear that foods regulate the physiological functions of the human body through their action on the immune, nervous, endocrine and other systems. It is also known that the intestine is equipped with an immune system, that the large bowel has intestinal flora, and that there is a cooperative relationship between the intestinal flora and the intestinal immune system. This review will deal with the effects of orally ingested functional components of food such as probiotics, prebiotics, vitamins and minerals on the mutualism between intestinal flora and the intestinal immune system as well as their effects on the systemic immune system. Furthermore, the relationship between the collapse of the mutualism and onset of diseases is discussed.
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.
We assessed the fecal bifidobacteria concentrations of 21 nursing home subjects prior to death and 21 age- and sex-matched controls. Bifidobacterial levels, determined by molecular methods, were in the range of those usually found in adults. Total fecal bifidobacterial concentrations determined by fluorescent in situ hybridization and quantitative real-time PCR tended to be lower, although not significantly, in subjects who subsequently died than in age- and sex-matched controls.
Pyrosequence-based 16S rRNA profiling has become a very powerful tool for visualizing the community structure of gastro-intestinal (GI) tract microbiota. The system was established with newly designed universal primers with barcode sequences and newly modified algorithms to convert batch sequence data to bacterial population data. In silico primer match simulation indicates that the primers, Q-968F, Q-1046R, and Q-1390R, match to almost of all 16S rRNAs in the database within one base mismatch, with especially high coverage ratios for the four biggest common phyla in human GI tract. Also, the new SeqmatchQ100 algorithm correctly assigns almost all of the target 60-base sequences of the 16S rRNA V6 region to the corresponding genus except for those from the Enterobacteriaceae family and the Enterococcus genus. Furthermore, the SeqmatchQ400 algorithm efficiently provides species-level population data from a 400-base sequence of the 16S rRNA V6-V8 region with the exceptions of the Enterobacteriaceae and Enterococcaceae families. A barcode-sequence tag strategy was used to analyze up to 128 samples at a time. With these newly prepared tools, pyrosequence-based 16S rRNA profiling displays community structures of GI-tract microbiota. For instance, establishment of bifidus flora in newborn infants and dynamics in the microbial community structure after weaning were effectively demonstrated by 16S rRNA profiling. In future, this analytical system should be of use for monitoring changes in GI-tract bacterial composition which may be influenced by diets, drugs, or sickness.
Intestinal microbiota have marked metabolic activity and influences the host in both beneficial and harmful ways. In the present study, we developed an apparatus to measure the amount of CO2 in the gas excreted during defecation and investigated whether this amount of CO2 can be used as an indicator of the intestinal environment. The apparatus consists of a fan and a commercial CO2 sensor attached to a toilet stool. Fecal pH, fecal water content, concentrations of short chain organic acids (SCFAs) and intestinal putrefactive products and composition of fecal microbiota were analyzed as indicators of the intestinal environment. The apparatus could measure the amount of CO2 in the gas with good reproducibility, irrespective of the open area at the top of the toilet stool, position of gas injection and composition of the gas. In a volunteer study, the amount of CO2 in defecation gas correlated with pH, water content and concentrations of SCFAs and intestinal putrefactive products in the feces, although correlation with the composition of intestinal microbiota was not be observed. The results indicate that the amount of CO2 in defecation gas can be measured with simple and sanitary procedures and is a good indicator of the intestinal environment.
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.
