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Resistance of germfree rats to indomethacin-induced intestinal lesions.

Indomethacin given orally to conventional rats produced in three days a syndrome, often fatal, of intestinal lesions characterized by multiple ulcers and peritonitis. Male germfree rats were found to be resistant to this effect of indomethacin, while female germfree rats developed very mild lesions. Germfree rats became sensitive again to such lesions when monocontaminated with E. coli. In such animals, however, the lesions were less severe than in conventional animals, presumably because more than one microorganism is necessary for the full syndrome to develop. These results suggest that microorganisms are necessary for the development of indomethacin-induced intestinal lesions. Secondary bile acids, absent in germfree animals, may also be necessary. The prostaglandin deficiency caused by indomethacin appears to weaken the resistance of the intestinal mucosa to microorganisms and/or their toxins. The latter may then penetrate the mucosa, damage the cells and produce ulcers and perforations. Since several prostaglandins also protect against indomethacin-induced lesions, the hypothesis is advanced that certain prostaglandins may protect the mucosa ("cytoprotection") by preventing the spread of microorganisms and/or their toxin through the intestinal wall.

Animals↗

Nucleosides are efficiently absorbed by Na(+)-dependent transport across the intestinal brush border membrane in veal calves.

In previous work, a comparatively high capacity for Na(+)-dependent transport of nucleosides across the intestinal brush border membrane (BBM) was observed in dairy cows, which might be related to digestion of the large amount of nucleic acids present in ruminal microorganisms in the ruminant small intestine. If this were the case, the capacity for Na(+)-dependent intestinal nucleoside transport should be much lower in veal calves, in which only small amounts of nucleic acids, nucleotides, and nucleosides reach the small intestine via the milk replacer. To test this hypothesis, we investigated Na(+)-dependent transport of 3H-labeled thymidine and guanosine across the BBM using BBM vesicles (BBMV) isolated from the small intestine of veal calves. In the presence of a transmembrane Na+ gradient both substrates were transported against a concentration gradient. Inhibitory studies showed that thymidine and guanosine are transported by two different transporters with overlapping substrate specificity, one accepting predominantly pyrimidine nucleosides (N2) and one accepting particularly purine nucleosides (N1). Nucleoside transport was inhibited by glucose along the whole small intestine. Maximal transport rates similar to those in dairy cows were obtained for the proximal, mid-, and distal small intestine. These findings suggest that the high absorptive capacity for nucleosides is a genetically fixed property in the bovine small intestine, which is already present in the preruminant state of veal calves. It may contribute to the high digestibility of nucleic acids observed by others in veal calves receiving milk replacer supplemented with RNA. Its main function may be the efficient absorption of nucleosides resulting from the digestion of nucleic acids associated with desquamated enterocytes. Due to the limited de novo synthesis of nucleotides in enterocytes intracellular uptake of nucleosides across the BBM may contribute to nucleic acid synthesis in enterocytes and thus may have a trophic effect on the intestinal epithelium.

Animals↗

Biotherapeutic agents. A neglected modality for the treatment and prevention of selected intestinal and vaginal infections.

OBJECTIVE: To evaluate the potential of biotherapeutic agents (microorganisms with therapeutic properties) for the prevention and/or treatment of selected intestinal and vaginal infections. DATA SOURCES: The MEDLINE database was searched for all relevant articles published between 1966 and September 1995. Search terms used were biotherapeutic agent, probiotic, Lactobacillus, Saccharomyces, Bifidobacterium, Candida, gastrointestinal- system, vaginitis, vaginosis-bacterial, and related terms. The bibliographies of obtained articles were also reviewed. STUDY SELECTION AND DATA EXTRACTION: All placebo-controlled human studies on biotherapeutic agents were reviewed. English-language open trials, case series and reports, and animal studies were reviewed only if they were especially relevant to providing information on the potential efficacy, adverse effects, or mechanisms of action of these agents. DATA SYNTHESIS: Placebo-controlled studies have shown that biotherapeutic agents have been used successfully to prevent antibiotic-associated diarrhea (Lactobacillus caseiGG, bifidobacterium longum, B longum with L acidophilus, and Saccharomyces boulardii), to prevent acute infantile diarrhea (Bifidobacterium bifidum with Streptococcus thermophilus), to treat recurrent Clostridium difficile disease (S boulardii), and to treat various other diarrheal illnesses (Enterococcus faecium SF68, L caseiGG, and S boulardii). There is also evidence for Lactobacillus acidophilus in the prevention of candidal vaginitis. Few adverse effects have been reported. However, many of the studies tested only small numbers of patients or volunteers. CONCLUSIONS: There is now evidence that administration of selected microorganisms is beneficial in the prevention and treatment of certain intestinal and, possibly, treatment of vaginal infections. In an effort to decrease the reliance on antimicrobials, the time has come to carefully explore the therapeutic applications of biotherapeutic agents.

Adult↗

Identification of coccoid Escherichia coli BJ4 cells in the large intestine of streptomycin-treated mice.

Escherichia coli BJ4, a rat isolate, was used to examine the growth and differentiation of the microorganism in its natural habitat, the intestine. Growth of E. coli BJ4 in the large intestine of streptomycin-treated mice was compared with its growth in laboratory media. By a number of methods, it was shown that E. coli BJ4 differentiates, during growth in the intestine, into two distinct populations, one that has the characteristics of the laboratory-grown strain and one that appears as a coccoid cell. Furthermore, it was shown that there is a natural selection for the coccoid-type cell in the intestine, while in laboratory media growth of rod-shaped E. coli BJ4 is enhanced.

Animals↗

Selective antimicrobial modulation of the intestinal tract by norfloxacin in human volunteers and in gnotobiotic mice associated with a human fecal flora.

Intestinal endogenous members of the family Enterobacteriaceae were eliminated in 12 human volunteers treated with 400 or 800 mg of oral norfloxacin per day for 5 days. No clones resistant to quinolone derivatives were isolated. Counts of aerotolerant streptococci were affected to various degrees, depending on their susceptibility to norfloxacin. During treatment, counts of anaerobes remained above 9.8 log10 CFU/g of feces. A total of 932 anaerobic isolates from the predominant flora (over 10(9) CFU/g) in fecal samples obtained before or during norfloxacin treatment were classified by a simple morphological and physiological scheme. The composition of this flora was fairly stable from one sample to another before treatment and was not substantially modified by norfloxacin. Intestinal resistance to colonization by exogenous microorganisms was studied in gnotobiotic mice associated with a human fecal flora. The composition of the fecal flora of the human donor and the fecal concentrations of norfloxacin in the volunteers were reproduced in the intestine of the mice. Resistance to colonization by exogenous microorganisms was reduced by norfloxacin for only 2 of 14 (14%) of the strains tested. These results suggest that norfloxacin is a good candidate for selective antimicrobial modulation of the intestinal tract in humans.

Animals↗

Properties of Na(+)-dependent nucleoside transport in the proximal and distal small intestine of cows.

Large amounts of nucleic acids associated with rumen microorganisms are digested in the proximal part of the small intestine of ruminants. We studied how the proximal-distal gradient in nucleic acid digestion is related to activity of Na(+)-nucleoside transporters in brush border membrane vesicles isolated from the proximal and distal small intestine of cows. Two Na(+)-dependent nucleoside transporters with overlapping substrate specificity were shown to be present at the two intestinal sites, one for pyrimidine nucleosides and one for purine nucleosides. Affinity constants (K(m)-values) for both thymidine and guanosine transport were similar at the two intestinal sites, while transport capacity (V(max)) was 2-3 times higher in the proximal than in the distal small intestine. Glucose and alpha-methyl-D-glucoside (0.1 mmol/l or 2 mmol/l) inhibited transport of thymidine and guanosine markedly only in the proximal small intestine. It is concluded that absorption of nucleosides by the two Na(+)-nucleoside transporters reflects the proximal-distal gradient in nucleic acid digestion.

Animals↗

[Proteus adhesion to intestinal epithelium].

The adhesive properties of Proteus strains isolated from different sources have been studied under conditions similar to the real interaction of microorganisms with the epithelial cells of intestine. A comparison of the adhesive properties of Proteus and of colon Bacillus has shown that the value of the strong adhesion to the mucosa of Proteus isolated under enterocolitis at the same bulk concentrations of the infectious suspension is 2-3 order less than that of E. coli. The adhesion of Proteus to the surface of epithelial cells begins at bulk concentrations exceeding those for the colon Bacillus by 3-4 orders. Besides, a toxic effect of number of freshly isolated Proteus strains on the epithelial cells of intestine mucosa is observed. Strains isolated from patients with diarrhea and from environment differed from each other in the studied criteria. A conclusion is drawn that at the initial stage of the interaction with the intestine mucosa the Proteus strains differ considerably from the indigenous strain of the colon Bacillus in the ability to colonize the epithelial surface.

Animals↗

Commensal bacteria increase invasion of intestinal epithelium by Salmonella enterica serovar Typhi.

The intestinal microflora consists of a heterogeneous population of microorganisms and has many effects on the health status of its human host. Here, it is shown that the products of certain strains of bacteria normally present in the intestinal microflora are able to trigger redistribution of the cystic fibrosis transmembrane conductance regulator (CFTR) protein in epithelial cells. CFTR is used by Salmonella enterica serovar Typhi as a receptor on epithelial cells which mediate the translocation of this microorganism to the gastric submucosa. Serovar Typhi-epithelial cell adhesion and CFTR-dependent invasion by serovar Typhi of epithelial cells were increased following commensal-mediated CFTR redistribution. These data suggest that commensal microorganisms present in the intestinal lumen can affect the efficiency of serovar Typhi invasion of the intestinal submucosa. This could be a key factor influencing host susceptibility to typhoid fever.

Animals↗

Immunization with live aroA recombinant Salmonella typhimurium producing invasin inhibits intestinal translocation of Yersinia pseudotuberculosis.

The Yersinia pseudotuberculosis inv gene encodes invasin, a 103-kDa outer membrane protein that allows bacteria to enter mammalian cells. The gene was subcloned into the attenuated aroA mutant of Salmonella typhimurium SL3261. Invasin was produced by the recombinant Salmonella strain and increased the ability of microorganisms to translocate from the intestinal lumen to the mesenteric lymph nodes. Specific antibodies for invasin were detected in sera and intestinal secretions of mice following oral immunization with the live Inv+ Salmonella strain. The immunization strongly inhibited intestinal translocation of Y. pseudotuberculosis when this pathogen was inoculated to mice but failed to prevent Yersinia dissemination from the gut lymphoid tissue.

3-Phosphoshikimate 1-Carboxyvinyltransferase↗

Differences in the development of the small intestine between gnotobiotic and conventionally bred piglets.

The effects of age, weaning and breeding conditions on the small intestinal morphology and the distribution of immunocompetent cells were investigated. The villus height and numbers of CD3+ T-lymphocytes, measured in the duodenum, jejunum and ileum, were determined in both the gnotobiotic and conventionally bred piglets. The diet of gnotobiotic piglets was composed of milk-replacement and feed mixtures. The application of milk replacement was finished on day 28. Conventional piglets were fed on sow's milk and feed mixtures. The animals were weaned on day 28. Small intestines were collected from 12 conventional and 12 gnotobiotic piglets slaughtered at the age of 2, 7, 14, 21, 28 and 35 days. The morphology results demonstrated that duodenal and ileal villi were significantly higher (p < 0.001) in gnotobiotic piglets during the entire period of the experiment. However, the weight of conventional piglets was higher during the experiment, in some cases significantly (p < 0.05). A marked reduction, in some cases significant (p < 0.001, p < 0.01 respectively), of the villi height on day 7 after the diet change for both groups of animals was recorded. The results demonstrate the differences in the gut development between both groups and their relationship to the breeding conditions. Nevertheless, the effect of crucial diet changes was observed independently of them. The immunohistochemistry results showed significantly (p < 0.001, p < 0.01 respectively) higher numbers of CD3+ T-lymphocytes in the jejunal villi of conventionally bred piglets. Similar results, in some cases significant (p < 0.001, p < 0.01 respectively), were also obtained from the other parts of the small intestine. These observations confirm reduced microorganism exposure under the gnotobiotic conditions.

Animals↗

Getting a grip on things: how do communities of bacterial symbionts become established in our intestine?

The gut contains our largest collection of resident microorganisms. One obvious question is how microbial communities establish and maintain themselves within a perfused intestine. The answers, which may come in part from observations made by environmental engineers and glycobiologists, have important implications for immunologists who wish to understand how indigenous microbial communities are accommodated. Here we propose that the mucus gel layer overlying the intestinal epithelium is a key contributor to the structural and functional stability of this microbiota and its tolerance by the host.

Animals↗

Probiotics inhibit enteropathogenic E. coli adherence in vitro by inducing intestinal mucin gene expression.

Probiotic agents, live microorganisms with beneficial effects for the host, may offer an alternative to conventional antimicrobials in the treatment and prevention of enteric infections. The probiotic agents Lactobacillus plantarum 299v and Lactobacillus rhamnosus GG quantitatively inhibited the adherence of an attaching and effacing pathogenic Escherichia coli to HT-29 intestinal epithelial cells but did not inhibit adherence to nonintestinal HEp-2 cells. HT-29 cells were grown under conditions that induced high levels of either MUC2 or MUC3 mRNA, but HEp-2 cells expressed only minimal levels of MUC2 and no MUC3 mRNA. Media enriched for MUC2 and MUC3 mucin were added exogenously to binding assays and were shown to be capable of inhibiting enteropathogen adherence to HEp-2 cells. Incubation of L. plantarum 299v with HT-29 cells increased MUC2 and MUC3 mRNA expression levels. From these in vitro studies, we propose the hypothesis that the ability of probiotic agents to inhibit adherence of attaching and effacing organisms to intestinal epithelial cells is mediated through their ability to increase expression of MUC2 and MUC3 intestinal mucins.

Bacterial Adhesion↗

Isolation of a rat intestinal Clostridium strain producing 5 alpha- and 5 beta-bile salt 3 alpha-sulfatase activity.

An unnamed sporeforming microorganism, termed Clostridium sp. strain S2, possessing bile salt sulfatase activity was isolated from rat intestinal microflora. The microorganism was a strictly anaerobic, nonmotile, gram-negative, asaccharolytic, sporeforming rod requiring CO2, vitamin K, and taurine; the guanine-plus-cytosine content of the DNA was 40.8 mol% (Tm), and the strain was tentatively classified as an atypical Clostridium species. Sulfatase activity was specific for 3 alpha-sulfate esters of 5 alpha- and 5 beta-bile salts, leaving the 3 beta-, 7 alpha-, and 12 alpha-sulfates unchanged. Strain S2 also deconjugated tauro- and glyco-conjugated bile salts and partially reduced into the corresponding 6 alpha-hydroxy bile salts. By these reactions, alpha-muricholate and beta-muricholate were more than 80% converted into hyocholate and omega-muricholate, respectively. In addition, strain S2 produced 12 alpha-hydroxysteroid dehydrogenase converting deoxycholate into 3 alpha-hydroxy-12-oxo-5 beta-cholanoate. When strain S2 was associated with gnotobiotic rats, the fecal bile salts were more than 90% desulfated and the fecal excretion of allochenodeoxycholate was five times lower than in control rats.

Animals↗

Lamina propria dendritic cells in the physiology and pathology of the gastrointestinal tract.

PURPOSE OF REVIEW: The mucosal immune system constantly surveys the intestinal microbiota. The outcome of this interaction is determined by the functional properties of dendritic cells, which play a key role in immune response by facilitating antigen sampling and pathogen recognition, as well as innate host defenses. RECENT FINDINGS: Recent advances have provided insight into the diverse mechanisms involved in the acquisition of intestinal antigens and led to a new appreciation of organ-specific functional subspecification of dendritic cell subsets. Dendritic cells are not a rare cell type in the intestine but populate the entire lamina propria of the gastrointestinal tract as an extensive network. Distinct dendritic cell subsets may be associated with specific immune functions in the lamina propria and Peyer's patches. Newly discovered routes of antigen acquisition, such as the formation of transepithelial dendrites, allow dendritic cells direct access to the intestinal lumen to obtain information about commensal and pathogenic microorganisms. Dendritic cells emerge as key regulators of the intestinal immune system with their ability to direct intestine-specific migration and control of T cells. SUMMARY: Dendritic cells play a major role in the complex interactions between the gut microbiota and the innate and adaptive immune system, leading to tolerance and immunity. Recent contributions have yielded important information that may aid in the development of novel therapeutic approaches to the treatment of inflammatory bowl disease and intestinal infections and to new immunization strategies.

Animals↗

[Intestinal microflora in workers of harmful industry].

Prolonged work in industry under unhealthy working conditions leads to disturbances in the normal intestinal microflora in employees. The content of bifidobacteria decreases simultaneously with an increase in the amount of opportunistic microorganisms. The degree of disturbances in intestinal microbiocenosis correlates with the length of service.

Adult↗

[Study of vaginal and intestinal microflora of women in the prenatal period and its correction in dysbacteriosis].

A comparative research of the structure of vaginal and intestinal microflora in norm and at kidney pathologies in women in the prenatal period was carried out. At physiologically normal course of pregnancy microbiocenosis of vagina and intestine does not contain pathogenic and conditional-pathogenic microorganisms. Lactic acid bacteria are fixed within the limits of 10(5)-10(8) CFU/1 ml in the vagina secretion and 10(7)-10(8) CFU/1 g in the intestine content. The spore microorganisms have completely disappeared in vaginal biocenosis of women with pyelonephritis after pharmacotherapy; and colibacterias has disappeared in 62% of women. Quantity of lactic acid bacteria has also decreased. Quantity of E. coli (10(8)- 10(9)) CFU/g, sporous microorganisms (10(3)-10(4)) CFU/g and yeast (10(4)-10(5)) CFU/g has considerably increased in the content of intestine. Lactic acid bacteria in content of the vagina are presented by: Lactobacillus acidophilus, L. plantarum, L. fermentum, L. vaginalis; in content of the intestine--L. plantarum and L. fermentum. All the isolated strains of lactobacilli are resistant to metrogyl and amphotericin, 87%--to cephoxitine, cypropfloxacine. Twenty three of 24 strains of lactic acid bacteria--antagonists of pathogenic microflora have shown adhesion to vaginal epthelium. The degree of adhesive activity depends on the strain and genus specificity of cultures. The highest index of adhesiveness in indicated in Enterococcus faecium (5.82 - 7.62) and Streptococcus salivarius subsp. thermophilus (2.74 - 6.40) strains. The screening of strains has been performed, which suppress growth of gas-producing microflora. The strain of Lactobacillus plantarum 200D proved to be the most active one. A complex of cultures of the lactic bacteria providing normalization of microbial cenosis of the vagina in women in the prenatal period has been selected as based on the data obtained. The biotechnology of production of vaginal suppositories is developed.

Administration, Intravaginal↗

[Influence of alum on intestinal flora in mice].

OBJECTIVE: To observe the influence of alum on the intestinal microecological balance in normal microorganisms. METHOD: The mice were administered orally with alum of a small dosage(0.25/kg) and a large dosage(1 g/kg) for half a month, two months and three months, and a micro flora analysis of the mice was carried out at intervals of the above mentioned administrations. RESULT: The intestinal flora in the animals administered with alum was imbalanced. The counts of bifidobacteria and lactobacilli closely related to human physiological activities were decreased. The counts of pathogenic E. Coli significantly increased; and the longer the animals were treated with alum, the stronger the microecological balance was influenced. CONCLUSION: Alum could induce imbalance of the normal intestinal flora in mice.

Alum Compounds↗

[Application of enteral detoxication and decontamination in acute ileus].

According to the experimental investigation data, conducted in 16 mongrel dogs in an acute ileus (AI), there are observed the colonization of proximal parts of small intestine (SI) by aerobic and anaerobic microorganisms, the power dependent processes of inhibition and activation of peroxidal oxidation of lipids in her mucosa, causing the disorders of her morphology. Conduction of intraoperative flowing intestinal lavage and the abdominal cavity sanation using betadin, diluted in 1:100 ratio, have promoted the pathological microorganisms quantity reduction and stimulation of power dependent processes in the SI mucosa. Application of enteral detoxication and decontamination in 86 patients with AI during performance and after the operation have permitted to reduce the intoxication severity, to restore the motor, evacuational, absorbtive function of SI, the postoperative complications frequency.

Acute Disease↗