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Biomedical subjects

Eduardo J Schiffrin

Publications and source records attributed to Eduardo J Schiffrin.

8 recordsLinked to original sources

Lactobacillus johnsonii La1 antagonizes Giardia intestinalis in vivo.

This study describes the in vivo activity of Lactobacillus johnsonii La1 (NCC533) in Giardia intestinalis-infected gerbils (Meriones unguiculatus). Daily administration of lactobacilli in the drinking water from 7 days before inoculation with Giardia trophozoites efficiently prevented G. intestinalis strain WB clone C6 from infecting gerbils. More specifically, shedding of fecal Giardia antigens (GSA65 protein) was diminished in the La1-treated group, and resolution of infection was observed by 21 days postinoculation. Histology and analysis of enzymatic markers of microvillus membrane integrity revealed that probiotic administration also protected against parasite-induced mucosal damage. In addition, a cellular response to Giardia antigens was stimulated in spleen cells from La1-treated gerbils. Results show for the first time the antigiardial effect of probiotic lactobacilli in vivo and provide further insight into the antagonistic properties of lactic acid bacteria against protozoa involved in intestinal infections.

Animals↗

Soluble forms of Toll-like receptor (TLR)2 capable of modulating TLR2 signaling are present in human plasma and breast milk.

Dysregulation of the initial, innate immune response to bacterial infection may lead to septic shock and death. Toll-like receptors (TLRs) play a crucial role in this innate immune response, and yet the regulatory mechanisms controlling microbial-induced TLR triggering are still to be fully understood. We have therefore sought specific regulatory mechanisms that may modulate TLR signaling. In this study, we tested for the possible existence of a functionally active soluble form of TLR2. We demonstrated the existence of natural soluble forms of TLR2 (sTLR2), which we show to be capable of modulating cell activation. We found that blood monocytes released sTLR2 constitutively and that the kinetics of sTLR2 release increased upon cell activation. Analysis of cells expressing the human TLR2 cDNA or its c-myc-tagged version indicated that sTLR2 resulted from the posttranslational modification of the TLR2 protein in an intracellular compartment. Moreover, an intracellular pool of sTLR2 is maintained. sTLR2 was found naturally expressed in breast milk and plasma. Milk sTLR2 levels mirrored those of the TLR coreceptor soluble CD14. Depletion of sTLR2 from serum resulted in an increased cellular response to bacterial lipopeptide. Notably, serum sTLR2 was lower in tuberculosis patients. Coimmunoprecipitation experiments and computational molecular docking studies showed an interaction between sTLR2 and soluble CD14 in plasma and milk. These findings suggest the existence of a novel and specific innate immune mechanism regulating microbial-induced TLR triggering, and may lead to new therapeutics for the prevention and/or treatment of severe infectious diseases.

Amino Acid Sequence↗

Supplementation of food with Enterococcus faecium (SF68) stimulates immune functions in young dogs.

The gut microflora play a crucial role in several physiologic functions of the host, including maturation of the gut-associated lymphoid tissues during the first months of life. Oral administration of probiotic lactic acid bacteria (LAB) modulates the immune system of humans and some laboratory animals. This effect has never been examined in dogs; therefore, our aim was to study the capacity of a probiotic LAB to stimulate immune functions in young dogs. Puppies were allotted to two groups receiving either a control diet or a diet supplemented with 5 x 10(8) colony forming units (cfu)/d of probiotic Enterococcus faecium (SF68) from weaning to 1 y of age. Fecal and blood samples were collected from the dogs at different time points for the measurement of fecal immunoglobulin (Ig)A, circulating IgG and IgA, and the proportions of lymphoid cell subsets. Fecal IgA and canine distemper virus (CDV) vaccine-specific circulating IgG and IgA were higher in the group receiving the probiotic than in controls. There were no differences in the percentages of CD4(+) and CD8(+) T cells between the groups, but the proportion of mature B cells [CD21(+)/major histocompatibility complex (MHC) class II(+)] was greater in those fed the probiotic. These data show for the first time that a dietary probiotic LAB enhance specific immune functions in young dogs, thus offering new opportunities for the utilization of probiotics in canine nutrition.

Animal Feed↗

Divergent patterns of colonization and immune response elicited from two intestinal Lactobacillus strains that display similar properties in vitro.

Lactobacilli derived from the endogenous flora of normal donors are being increasingly used as probiotics in functional foods and as vaccine carriers. However, a variety of studies done with distinct strains of lactobacilli has suggested heterogeneous and strain-specific effects. To dissect this heterogeneity at the immunological level, we selected two strains of lactobacilli that displayed similar properties in vitro and studied their impact on mucosal and systemic B-cell responses in monoxenic mice. Germfree mice were colonized with Lactobacillus johnsonii (NCC 533) or Lactobacillus paracasei (NCC 2461). Bacterial loads were monitored for 30 days in intestinal tissues, and mucosal and systemic B-cell responses were measured. Although both Lactobacillus strains displayed similar growth, survival, and adherence properties in vitro, they colonized the intestinal lumen and translocated into mucosal lymphoid organs at different densities. L. johnsonii colonized the intestine very efficiently at high levels, whereas the number of L. paracasei decreased rapidly and it colonized at low levels. We determined whether this difference in colonization correlated with an induction of different types of immune responses. We observed that colonization with either strain induced similar germinal center formation and immunoglobulin A-bearing lymphocytes in the mucosa, suggesting that both strains were able to activate mucosal B-cell responses. However, clear differences in patterns of immunoglobulins were observed between the two strains in the mucosa and in the periphery. Therefore, despite similar in vitro probiotic properties, distinct Lactobacillus strains may colonize the gut differently and generate divergent immune responses.

Animals↗

Intestinal microflora and homeostasis of the mucosal immune response: implications for probiotic bacteria?

The intestinal microflora can be considered a postnatally acquired organ that is composed of a large diversity of bacteria that perform important functions for the host and can be modulated by environmental factors, such as nutrition. Specific components of the intestinal microflora, including lactobacilli and bifidobacteria, have been associated with beneficial effects on the host, such as promotion of gut maturation and integrity, antagonisms against pathogens and immune modulation. Beyond this, the microflora seems to play a significant role in the maintenance of intestinal immune homeostasis and prevention of inflammation. The contribution of the intestinal epithelial cell in the first line of defense against pathogenic bacteria and microbial antigens has been recognized. However, the interactions of intestinal epithelial cells with indigenous bacteria are less well understood. This review will summarize the increasing scientific attention to mechanisms of the innate immune response of the host towards different components of the microflora, and suggest a potential role for selected probiotic bacteria in the regulation of intestinal inflammation.

Animals↗

Effect of Lactobacillus johnsonii La1 and antioxidants on intestinal flora and bacterial translocation in rats with experimental cirrhosis.

BACKGROUND/AIMS: Probiotics and antioxidants could be alternatives to antibiotics in the prevention of bacterial infections in cirrhosis. The aim of the present study was to determine the effect of Lactobacillus johnsonii La1 and antioxidants on intestinal flora, endotoxemia, and bacterial translocation in cirrhotic rats. METHODS: Twenty-nine Sprague-Dawley rats with cirrhosis induced by CCl(4) and ascites received Lactobacillus johnsonii La1 10(9)cfu/day in vehicle (antioxidants: vitamin C+glutamate) (n=10), vehicle alone (n=11), or water (n=8) by gavage. Another eight non-cirrhotic rats formed the control group. After 10 days of treatment, a laparotomy was performed to determine microbiological study of ileal and cecal feces, bacterial translocation, endotoxemia, and intestinal malondialdehyde (MDA) levels as index of intestinal oxidative damage. RESULTS: Intestinal enterobacteria and enterococci, bacterial translocation (0/11 and 0/10 vs. 5/8, P<0.01), and ileal MDA levels (P<0.01) were lower in cirrhotic rats treated with antioxidants alone or in combination with Lactobacillus johnsonii La1 compared to cirrhotic rats receiving water. Only rats treated with antioxidants and Lactobacillus johnsonii La1 showed a decrease in endotoxemia with respect to cirrhotic rats receiving water (P<0.05). CONCLUSIONS: Antioxidants alone or in combination with Lactobacillus johnsonii La1 can be useful in preventing bacterial translocation in cirrhosis.

Animals↗

Milk casein-based diet containing TGF-beta controls the inflammatory reaction in the HLA-B27 transgenic rat model.

BACKGROUND: A casein-based formula containing TGF-beta has been successfully used in adolescents during acute episodes of Crohn's disease. The role played by this molecule requires confirmation. We have examined the capacity of a TGF-beta containing diet to control the intestinal inflammation in HLA-B27 transgenic rats, and compared its effects with a similar diet devoid of TGF-beta. METHODS: Three groups of rats were studied. HLA-B27/hbeta2M transgenic rats were fed with a casein-based rat-adapted diet containing TGF-beta or a control casein-based diet without TGF-beta. Fischer control animals were fed the latter. Body weight, dietary intake, tissue weights, fecal samples, leukocyte counts, and acute phase response were analyzed. Intestinal inflammation was assessed by histology, myeloperoxidase, and mRNA expression of cytokines. MUC2 protein expression was assessed by immunohistochemistry. Breakdown of muscle protein was examined. RESULTS: The test diet improved diarrhea increasing the fecal dry matter and the colonic inflammation as shown by a lower inflammatory score (2.43 +/- 1.13 vs 4.42 +/- 0.53, p < .05), lower mucosal thickness (431.25 +/- 72.29 vs 508.57 +/- 81.32 microm, p = .08) and decreased IFNgamma mRNA expression. MUC2 protein expression was increased in HLA rats fed the TGF-beta diet compared with HLA rats fed the control diet, but restitution to normal pattern was not observed. The test diet also decreased leukocytosis and the acute phase response and improved the muscle catabolic response. CONCLUSION: The TGF-beta containing diet has a beneficial effect in an animal model of intestinal inflammation. Our observations support a potential role for dietary TGF-beta in the restoration of immune homeostasis.

Acute-Phase Reaction↗