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T Midtvedt

Publications and source records attributed to T Midtvedt.

At least 19 recordsLinked to original sources
PubMed1999

Estimation of growth rates of Escherichia coli BJ4 in streptomycin-treated and previously germfree mice by in situ rRNA hybridization.

The growth physiology of Escherichia coli during colonization of the intestinal tract was studied with four animal models: the streptomycin-treated mouse carrying a reduced microflora, the monoassociated mouse with no other microflora than the introduced strain, the conventionalized streptomycin-treated mouse, and the conventionalized monoassociated mouse harboring a full microflora. A 23S rRNA fluorescent oligonucleotide probe was used for hybridization to whole E. coli cells fixed directly after being taken from the animals, and the respective growth rates of E. coli BJ4 in the four animal models were estimated by correlating the cellular concentrations of ribosomes with the growth rate of the strain. The growth rates thus estimated from the ribosomal content of E. coli BJ4 in vivo did not differ in the streptomycin-treated and the monoassociated mice. After conventionalization there was a slight decrease of the bacterial growth rates in both animal models.

Animals↗
PubMed1999

Gas supersaturation in the cecal wall of mice due to bacterial CO2 production.

PCO2 in the lumen and serosa of cecum and jejunum was measured in mice. The anesthetic used was a fentanyl-fluanisone-midazolam mixture. PCO2 was recorded in vivo and postmortem. PCO2 was 409 +/- 32 Torr (55 +/- 4 kPa) in the cecal lumen and 199 +/- 22 Torr (27 +/- 3 kPa) on the serosa in normal mice. Irrigation of the cecum resulted in serosal and luminal PCO2 levels of 65-75 Torr. Cecal PCO2 was significantly lower in germ-free mice (65 +/- 5 Torr). Cecal PCO2 increased significantly after introduction of normal bacterial flora into germ-free mice. Introduction of bacterial monocultures into germ-free mice had no effect. After the deaths of the mice, cecal PCO2 increased rapidly in normal mice. The intestinal bacteria produced the majority of the cecal PCO2, and the use of tonometry in intestinal segments with a high bacterial activity should be interpreted with caution. We propose that serosal PCO2 levels >150-190 Torr (20-25 kPa) in the cecum of mice with a normal circulation may represent a state of gas supersaturation in the cecal wall.

Animals↗
PubMed1998

[Clostridium difficile-associated diarrhea treated with homologous feces].

The incidence of Clostridium difficile-associated diarrhoea has increased during the last few years. Treatment with vankomycin or metronidazol is usually effective, but relapses are not uncommon. Some good results have been reported with faecal enemas, but it is a controversal form of treatment. 18 patients with C. difficile-associated diarrhoea were given homologous faeces from one healthy donor. In 17 patients faeces was instillated via a coloscope and in one patient via a gastrostoma. C. difficile toxin was detected in all patients. Three patients with severe colitis did not respond to the treatment. The remaining patients were clinically cured, and no relapses were observed. Treatment of C. difficile-associated diarrhoea with faeces appears to be an alternative in moderate cases. In our limited number of patients we observed a poor correlation between the clinical picture, the endoscopic findings and the histological findings in colon biopsies. The ethical aspects of treatment with faeces will continue to be subject to discussion.

Adult↗
PubMed1998

Increased antibody production against gut-colonizing Escherichia coli in the presence of the anaerobic bacterium Peptostreptococcus.

Germ-free rats were colonized with E. coli alone, or with E. coli plus Lactobacillus acidophilus and a strain of the obligate anaerobic gram-positive species, Peptostreptococcus. The presence of Peptostreptococcus reduced translocation of E. coli, but increased the serum antibody response to E. coli antigen. Whereas the immunoglobulin G (IgG) anti-E. coli antibodies largely represented cross-reactive antibodies, those of the immunoglobulin M (IgM) isotype represented true anti-E. coli antibodies because they could not be absorbed by L. acidophilus or Peptostreptococcus but could with E. coli. We suggest that peptostreptococci prime the gut immune system to other bacterial antigens and that this could be a mechanism behind the reduced translocation of facultative anaerobes in the presence of obligate anaerobes.

Absorption↗
PubMed1998

Faecal short-chain fatty acids in patients with antibiotic-associated diarrhoea, before and after faecal enema treatment.

BACKGROUND: Antibiotic-associated diarrhoea (AAD) may range from mild disturbances to severe pseudomembranous colitis. Many antibiotics affect several intestinal microflora-associated characteristics, such as short-chain fatty acid (SCFA) pattern. In the present study we investigated SCFAs in 31 patients on admittance to the hospital for severe AAD. Nine patients were followed up more extensively after they had received an enema containing faecal microflora from a healthy person on a Western diet. METHODS: Faecal SCFAs were determined by gas chromatography. The enema was characterized before use. RESULTS: AAD patients showed significant disturbances in faecal SCFA pattern. Clinically, most enema-treated patients recovered within days and had no relapses within 18 months. CONCLUSIONS: Intestinal microflora showed great disturbances, and the amounts of SCFAs were reduced, although the diarrhoea was not related to total amount SCFAs. Administration of a faecal enema resulted in the clinical recovery of most patients with severe diarrhoea within 4 days.

Adult↗
PubMed1998

Routine perioperative antibiotic prophylaxis in renal transplantation.

BACKGROUND: Perioperative antibiotic prophylaxis may prevent infection following renal transplantation but it also contributes to development of resistant microorganisms. With refined surgical techniques, improved graft preservation, and immunosuppressive monitoring during recent decades one can question the present use of perioperative antibiotic prophylaxis. We retrospectively evaluated the incidence of infection in our renal transplant centre where antibiotic prophylaxis is not routinely used in renal recipients. Concurrently we performed a survey of perioperative antibiotic use to establish the current world-wide practice. METHODS: Infection episodes were evaluated from records of 448 adult renal transplant recipients (January 1994 to August 1996) at our centre. A questionnaire was mailed to 103 centres addressing the number of kidney transplantations in 1995, donor source (living vs cadaveric) and details on use of perioperative antibiotic prophylaxis. RESULTS: Single-centre study. Renal transplantation was performed without antibiotic prophylaxis in 377 patients (84%). Thirteen patients (3.4%) had early postoperative infections, nine with urinary-tract infection tended to have urinary catheter for a longer period than those without infection (5.0 +/- 2.7 vs 3.4 +/- 1.4 days, P = 0.27) and cadaveric kidney recipients to have higher incidence of infections (4.5 vs 1.5% P = 0.14). All infection episodes were successfully treated. The infection incidence in 71 (16%) 'high-risk' patients selected for antibiotic treatment was 4.2%. World-wide survey. Data were obtained from 101 centres in five continents representing 10532 renal transplants. Ninety centres (89%) used perioperative antibiotic prophylaxis. CONCLUSION: The infection incidence in patients who did not receive perioperative antibiotic prophylaxis was the same as in a small group of selected patients who received prophylaxis. The incidence was lower than usually reported in the literature. In contrast perioperative antibiotic prophylaxis is given to all patients in almost 90% of transplant centres worldwide. A reduction of prophylactic antibiotic use is encouraged.

Adult↗
PubMed1998

Creating and maintaining the gastrointestinal ecosystem: what we know and need to know from gnotobiology.

Studying the cross talk between nonpathogenic organisms and their mammalian hosts represents an experimental challenge because these interactions are typically subtle and the microbial societies that associate with mammalian hosts are very complex and dynamic. A large, functionally stable, climax community of microbes is maintained in the murine and human gastrointestinal tracts. This open ecosystem exhibits not only regional differences in the composition of its microbiota but also regional differences in the differentiation programs of its epithelial cells and in the spatial distribution of its component immune cells. A key experimental strategy for determining whether "nonpathogenic" microorganisms actively create their own regional habitats in this ecosystem is to define cellular function in germ-free animals and then evaluate the effects of adding single or several microbial species. This review focuses on how gnotobiotics-the study of germ-free animals-has been and needs to be used to examine how the gastrointestinal ecosystem is created and maintained. Areas discussed include the generation of simplified ecosystems by using genetically manipulatable microbes and hosts to determine whether components of the microbiota actively regulate epithelial differentiation to create niches for themselves and for other organisms; the ways in which gnotobiology can help reveal collaborative interactions among the microbiota, epithelium, and mucosal immune system; and the ways in which gnotobiology is and will be useful for identifying host and microbial factors that define the continuum between nonpathogenic and pathogenic. A series of tests of microbial contributions to several pathologic states, using germ-free and ex-germ-free mice, are proposed.

Animals↗
PubMed1997

Regional phenotypic specialization of intraepithelial lymphocytes in the rat intestine does not depend on microbial colonization.

Recent studies in mice and humans have provided evidence for regional specialization of gut intraepithelial lymphocytes (IEL). Here the authors report striking regional variability in the composition of IEL in rat small and large intestine. Two-colour immunofluorescence in situ analysis showed that the distribution of the CD3+ and CD3- IEL subpopulations varied, the proportion of T cells (CD3+) being higher in the ileum than in the jejunum and smallest in the colon. These differences were explained by variable numbers of the T-cell receptor (TCR)alpha/beta + (both CD8+ and CD4+) but not the TCR gamma/delta + subset. Moreover, the various IEL subpopulations showed distinct intraepithelial distribution patterns with CD4+ and CD8 alpha beta + T cells situated near the lamina propria, while CD3- IEL were located preferentially towards the adluminal part of the epithelium. Regional phenotypic variation did not depend on intestinal colonization because analogous results were obtained in germ-free rats. Conventionalization nevertheless caused a marked relative increase of small intestinal TCR alpha/beta + but not TCR gamma/delta + IEL. This increase was more sustained in the jejunum than ileum and eventually reduced the phenotypic IEL differences between the two sites. By contrast, microbial colonization of the colon induced only a transient increase of intraepithelial TCR alpha/beta + cells with no permanent phenotypic alterations. Both CD3+ and CD3- IEL contained subpopulations that expressed NKR-P1 independent of intestinal colonization. These results demonstrate phenotypic specialization of IEL at different levels of the gut and suggest that the indigenous flora is not essential to this end.

Animals↗
PubMed1997

Germ-free and conventional animal models for intestinal carbohydrate disposition.

Under conventional (CONV) conditions, the microbial flora is capable of breaking down most dietary derived carbohydrates as well as complex carbohydrates (glycolipids, glycoproteins, etc.) from the host. The major end products of these processes are short-chain fatty acids (SCFAs). In non-ruminants, most of the fermentation takes place in the large bowel. In ruminants, however, most acids are formed more proximal in the gastrointestinal (GI) tract. These microbial derived products may influence upon many host related functions, locally in the GI tract as well as elsewhere in the body. In germ-free (GF) animals, neglectable amounts of SCFAs are found in faeces. Parallel studies in GF and CONV animals given a standardized diet and ex-GF animals, receiving the same diet and mono/poly-associated with known microbial species, represent excellent models for answering such questions as (i) what can the microbes do? and (ii) what have the microbes done? These models allow detailed studies of the complex interplay between the host, his diet and his GI flora.

Animals↗
PubMed1997

Sulphasalazine, olsalazine and sulphapyridine induce mitogenic actions in the rat intestinal epithelium.

Our aim was to study the influence of sulphasalazine (SASP), olsalazine (ADS) and sulphapyridine (SP) on the cell kinetics of the intestinal epithelium in conventional rats. Groups of rats were treated with SASP, ADS or SP for 9 days. After an intraperitoneal injection of a metaphase blocker, the rats were killed and the jejunum, ileum and colon were examined in histological sections by means of the cumulative mitotic index (MI), growth fraction and number of cells in crypts and villi. SP increased both the MI in the jejunum, ileum and colon and the number of crypt cells (p < 0.05 vs controls). In contrast, SASP and ADS increased the MI only in the colonic epithelium (p < 0.05 vs controls). The growth fraction was essentially unaffected. Our results suggest that SASP, SP and ADS have a selective compartment-dependent proliferative action on the epithelium of the intestinal tract.

Aminosalicylic Acids↗
PubMed1997

Escherichia coli K5 capsule expression enhances colonization of the large intestine in the gnotobiotic rat.

The role of capsule expression in the capacity of Escherichia coli to colonize in the large intestinal environment was studied in a gnotobiotic rat model. The rats were given perorally a mixture of two mutant strains differing in K5 expression. After 2 weeks, the rats were sacrificed, and subsequently intestinal contents, intestinal mucosae, and mesenteric lymph nodes were homogenized and bacterial numbers were quantified. Two E. coli mutant pairs were used, the first pair (972-998) lacking the O-specific side chain and the second pair (973-997) carrying the O75 lipopolysaccharide. The K5+ mutants established themselves at a higher level than the K5- mutants (10(9) versus 10(6) CFU/g [P < 0.001] for the first pair and 10(9) versus 10(8) CFU/g [P < 0.01] for the second pair, respectively). The results were confirmed by serology showing a K5+ phenotype for practically all isolates. The bacterial population associated with the mucosa was similar to that in the luminal contents with respect to the proportions of the respective mutants, and translocation occurred in numbers proportional to the intestinal population densities of the respective mutants. All mutants were able to express type 1 as well as P fimbriae. After colonization, the expression of P fimbriae remained high whereas only a minority of the isolates expressed type 1 fimbriae. The results suggest that capsule expression and P fimbriae enhance intestinal colonization by E. coli and that these virulence factors, by increasing bacterial densities in the intestine, secondarily increase translocation.

Adhesins, Escherichia coli↗
PubMed1997

Endogenous prostaglandins and microflora modulate DNA synthesis and neuroendocrine peptides in the rat gastrointestinal tract.

BACKGROUND: Previous studies suggest that E2 prostaglandins and the microflora may participate in the regulation of endocrine cells and of gastrointestinal cell kinetics. Our aim is to examine the actions of endogenous prostaglandins and of the microflora on gastrointestinal cell proliferation and tissue levels of neuroendocrine peptides. METHODS: Germfree and ex-germfree rats were treated with subcutaneous placebo or 1.5 mg/kg indomethacin for 3 days. All rats were labeled with 3H-methyl-thymidine, and biopsy specimens from different parts of the gastrointestinal tract were processed for autoradiography. DNA synthesis was estimated by the labeling index, except in the oxyntic mucosa, where the total number of labeled cells present in 7.5 mm mucosa was used. The concentration of neuroendocrine peptides was determined by radioimmunoassay. RESULTS: In the germfree rat, indomethacin reduced DNA synthesis in the fundus, duodenum, and proximal jejunum (P < 0.05) and the number of villous cells throughout the small intestine (P < 0.05). Exposure to microflora increased DNA synthesis in the proximal and distal jejunum, ileum, and colon (P < 0.05 versus germfree controls) and the number of crypt cells in the distal small intestine and colon (P < 0.05) and reduced the number of villous cells in the small intestine (P < 0.05) but did not affect tissue concentrations of neuroendocrine peptides. Indomethacin increased the concentration of somatostatin in the stomach, duodenum, and colon of germfree rats (P < 0.001), the concentration of calcitonin gene-related peptide (CGRP) and enteroglucagon in the proximal and distal jejunum and ileum (P < 0.001), and the concentration of glucagon in the colon (P < 0.05). The concentrations of somatostatin, CGRP, and glucagon were lower in indomethacin-treated ex-germfree rats than in indomethacin-treated germfree rats (P < 0.01). CONCLUSIONS: Indomethacin selectively reduced DNA synthesis in the upper gastrointestinal tract of germfree rats, indicating a basal stimulatory role for endogenous prostaglandins on cell proliferation. Endogenous prostaglandins modulate synthesis or release of gastrointestinal neuroendocrine peptides. Somatostatin may mediate indomethacin-induced reduction of DNA synthesis. The microflora stimulates cell proliferation and influences tissue levels of neuroendocrine peptides in a manner opposite to that of indomethacin.

Animals↗
PubMed1996

A model of host-microbial interactions in an open mammalian ecosystem.

The maintenance and significance of the complex populations of microbes present in the mammalian intestine are poorly understood. Comparison of conventionally housed and germ-free NMRI mice revealed that production of fucosylated glycoconjugates and an alpha1, 2-fucosyltransferase messenger RNA in the small-intestinal epithelium requires the normal microflora. Colonization of germ-free mice with Bacteroides thetaiotaomicron, a component of this flora, restored the fucosylation program, whereas an isogenic strain carrying a transposon insertion that disrupts its ability to use L-fucose as a carbon source did not. Simplified models such as this should aid the study of open microbial ecosystems.

Animals↗
PubMed1996

Microbial colonization influences composition and T-cell receptor V beta repertoire of intraepithelial lymphocytes in rat intestine.

Studies in mice have shown that the composition of intestinal intraepithelial lymphocytes (IEL) may be markedly altered by gut microbial colonization. Such modulation was studied in a rat model by the use of germ-free and conventionalized animals from which IEL from the small intestine were isolated and analysed by flow cytometry. Conventionalization caused expansion as well as phenotypic alterations of T-cell receptor (TCR) alpha/beta + IEL in that the proportions of CD4+ and CD8 alpha beta + TCR alpha/beta + cells were increased, while the double negative (CD4- CD8-) fraction was reduced. microbial colonization also influenced the TCR V beta repertoire of CD8+ IEL in that the proportions of V beta 8.2+ and V beta 10+ cells were increased, whereas V beta 8.5+ and V beta 16+ cells were relatively decreased. Moreover, conventionalization influenced the levels of TCR cell surface expression in the same V beta subsets. Three-colour flow-cytometric analysis demonstrated that skewing of the V beta repertoire was most pronounced in the CD8 alpha alpha + subset, although the numerical increase of IEL mainly included the CD8 alpha beta + subset. In contrast to IEL, the TCR V beta repertoire in mesenteric lymph nodes was unchanged after intestinal colonization. These results confirm that TCR alpha/beta + IEL subpopulations respond dynamically to the microbial gut flora and suggest that their V beta repertoire can be shaped by luminal microbial antigens.

Animals↗
PubMed1995

[Microbiology and ecology--the microbe aspect].

Invisible microbes play very important roles in all ecosystems. Living generally in harsh and seemingly inhospitable places all around, they reveal a remarkable potential and resilience of life. In all microbial ecosystems, antimicrobial substances, as antibiotics, are of crucial regulatory importance. In modern human and veterinarian medicine, about 50 million kilos of potent antibiotics are used every year. Some of these substances are very persistent in the ecosystem, i.e. they remain in the natural environment for a very long time. Now the microbial empire is striking back, and increasing resistance towards antibiotics is becoming a global problem. The need for a proper future strategy is underlined.

Anti-Bacterial Agents↗
PubMed1995

Intestinal microbial bile acid transformation in healthy infants.

Following the establishment of functionally active intestinal flora in three healthy Swedish children from birth up to 24 months of age, we investigated the development of different 24-carbon bile acids. The fecal bile acids were group-separated into unconjugated, glycine-conjugated, taurine-conjugated, and sulfated, so that we could follow the changes between the different fractions of conjugates. In meconium, most (55-63%) of the bile acids were conjugated with taurine; only 11-32% were conjugated with glycine. Deconjugation was the first sign of intestinal microbial activity on the bile acids. Already at 1 month of age, most of the bile acids were deconjugated; among the conjugated bile acids, the glycine-conjugated dominated over the taurine-conjugated. An unidentified conjugate of cholic and chenodeoxycholic acids (C, CDC) that separated with the sulfated bile acids was found. The unconjugated bile acids and those that arose from hydrolysis of existing conjugates were separated and identified by gas-liquid chromatography coupled to mass spectrometry (GC-MS). Twenty-nine different bile acids were identified. In meconium, 16 different bile acids were identified. C and CDC were identified in all samples. The bile acid pattern changed during the course of the study. Many of the identified bile acids were only found in one or a few of the analyzed samples, and sometimes only in samples from one child. 6 alpha-hydroxylated bile acids, probably not microbially synthesized, were present at high percentages in the children.(ABSTRACT TRUNCATED AT 250 WORDS)

Bifidobacterium↗