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PubMed1997

The protective role of gastric acidity in neonatal bacterial translocation.

The acid environment of the stomach serves as an important defense against intestinal colonization by potentially pathogenic bacteria. The purpose of this study was to examine the effect of increased gastric pH on bacterial translocation in a neonatal rabbit model. Fifty-nine rabbit pups were delivered by cesarean section and randomly divided into normal acid (NA) and reduced acid (RA) groups. All were gavage fed and challenged with Enterobacter cloacae, 1 x 10(6) CFU/mL. The RA group received ranitidine, 20 mg/kg/d with all feeds. Gastric pH was measured by pH probe before and 4 hours after bacterial challenge. Mesenteric lymph node (MLN), spleen, liver, midjejunum, and cecum were harvested for culture at 72 hours. Gastric pH in the RA group was significantly increased before and 4 hours after the bacterial challenge. The incidence of bacterial translocation to the MLN, spleen, and liver was significantly higher in the RA group. Log cecal and jejunal colony counts were significantly increased in the RA animals. The authors conclude that the gastric acidity is protective against intestinal colonization and translocation of potentially pathogenic bacteria in this neonatal rabbit model.

Animals↗
PubMedDate not supplied

Evaluation of the efficacy of Broilact in preventing infection of broiler chicks with Salmonella enteritidis PT4.

A study was conducted to evaluate treatment of day-old broiler chicks with Broilact, a live-culture preparation, for preventing intestinal colonization by a non-host-specific Salmonella (S. enteritidis PT4, with high resistance to nalidixic acid). Newly hatched broiler chicks were sprayed with Broilact at a commercial hatchery and delivered on the same day to Huntingdon Research Centre. Control chicks from the same source (i.e. chicks not treated with Broilact) were sent separately. Chicks were maintained in floor pens in groups of 40. The challenge was introduced by means of seeder birds infected with S. enteritidis PT4 (nalr) at a nominal dose level of 10(4) CFU per bird (3 seeder birds per pen of 40 contact birds). Groups of birds were killed 7, 28 and 40 days after challenge, and in each case caecal contents were examined culturally for the test organism. A total of 18 deaths occurred including 13 untreated contact birds, 3 Broilact-treated contact birds and 2 seeder birds. These were attributed to the experimental infection. Results of the examination of caecal contents from untreated control birds indicated that the challenge organism was successfully established in contact chicks via the seeder birds. The overall results for birds treated with Broilact showed a clear protective effect, with little indication of any significant infection by the challenge organism. It was concluded therefore that under the conditions of this study, Broilact was largely effective in preventing intestinal colonization by the non-host-specific s. enteritidis PT4.

Animals↗
PubMed1977

The intestinal mucosal barrier to intact antigenic protein. Difference between colon and small intestine.

The integrity of the normal mature intestinal mucosal barrier to unaltered proteins was evaluated with tritiated bovine albumin in rats. Intact H3-BSA placed into either colon or small intestinal lumen regularly reached the bloodstream in quantities sufficient to be antigenic or toxigenic, although the fraction of H3-BSA absorbed from the colon (0.13 per cent) was significantly smaller than that absorbed from the small intestine (1.7 per cent). These studies support the possibility that uptake of ingested or bacterial antigens from the normal gut may be involved in the pathogenesis of local intestinal and systemic disease in man.

Animals↗
PubMed1994

Colonization of intestinal bacteria in the normal neonate: comparison between mouth and rectal swabs and small and large bowel specimens.

Seventy-four New Zealand white rabbit pups were divided into four groups: group I, 2 days of age (n = 9); group II, 3 to 5 days of age (n = 24); group III, 6 to 8 days of age (n = 27); and group IV, 10 to 13 days of age (n = 14). Mouth swabs (MS), rectal swabs (RS), small bowel specimens (SB), and large bowel specimens (LB) were obtained from each rabbit, incubated for 24 hours in thioglycolate broth, and plated on blood agar in aerobic and anaerobic environments. After 24 hours, growth on blood agar plates were observed. All MS specimens and all but one RS specimen showed positive growth. Growth of both LB and SB specimens increased significantly with age (P < .04). In addition, SB growth was significantly less than RS or MS growth in groups I, II, and III (P < .05). LB growth was significantly less than RS or MS growth in group I (P < .01) and tended to be less in groups II and III (62.5% v 100% and 93% v 100%, respectively). These data show that nearly half of normal rabbits under 6 days of age have sterile small and large intestines despite almost 100% growth from rectal and mouth swabs. These findings partially explain the absence of spontaneous bacterial translocation in young rabbit pups (under 4 days of age) and have important implications for the prophylaxis and treatment of neonatal sepsis.

Animals↗
PubMed2005

Vibrio cholerae persistence in aquatic environments and colonization of intestinal cells: involvement of a common adhesion mechanism.

Forty-one Tnpho A mutants of Vibrio cholerae O1 classical strain CD81 were analyzed for their ability to interact with chitin particles, Tigriopus fulvus copepods and the Intestine 407 cell line compared to the parent strain. Thirteen mutants were less adhesive than CD81; in particular, T21, T33 and T87 were less adhesive towards all substrates and insensitive to inhibition by N-acetyl glucosamine (GlcNAc). By SDS-PAGE analysis of sarkosyl-insoluble membrane proteins (siMPs) isolated from mutants and parent, it was found that a 53 kDa siMP is missing in T21, T33 and T87 mutants. It is hypothesized that this protein might have the function to mediate adherence to GlcNAc-containing substrates both in the aquatic environment and in human intestine.

Animals↗
PubMed1999

Lipopolysaccharide- and proinflammatory cytokine-induced energy production in intestinal and colonic epithelial cell lines.

BACKGROUND: Although epithelial cells in ulcerative colitis may be metabolically deficient, it remains unknown whether epithelial cells modulate energy metabolism in inflamed mucosa. The purpose of the present study is to investigate whether inflammatory mediators such as lipopolysaccharide (LPS), interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha) alter energy metabolism in epithelial cells. METHODS: Adenosine 5'-triphosphate (ATP) levels in HT29 cells cultured with LPS, IL-1beta, IL-6, or TNF-alpha were measured with high-performance liquid chromatography, using a reversed-phase chromatography column. Cellular and mitochondrial (antimycin A-sensitive) respiration rates were determined polarographically, using a Clark-type oxygen electrode. RESULTS: When the cells were cultured with LPS, IL-6, and TNF-alpha but not IL-1beta, ATP levels increased significantly at 6 h, followed by a decrease at 24 h. Enhancement of oxygen consumption, which was completely blocked by antimycin A, was also shown at 3 h by the exposure to these substrates. CONCLUSION: LPS and proinflammatory cytokines induced cellular ATP generated by mitochondrial phosphorylation. An active energy production in epithelial cells on the exposure to inflammatory mediators may be critical for escape from chronic mucosal inflammation.

Adenosine Triphosphate↗
PubMed1988

Toxin, toxin-coregulated pili, and the toxR regulon are essential for Vibrio cholerae pathogenesis in humans.

Isogenic mutant strains of V. cholerae O1 lacking elements of a genetic regulon controlled by toxR and implicated in virulence were tested in volunteers. A deletion mutation in ctxA, the gene encoding the A subunit of cholera toxin, markedly attenuated disease symptoms without affecting intestinal colonization. Deletion of toxR, the gene encoding the cholera toxin-positive regulatory protein resulted in a diminution in colonizing capacity. A deletion mutation in tcpA, encoding the major subunit of the toxin coregulated pilus (regulated by toxR), abolished the colonizing capacity of this strain. These results show for the first time the role of a specific pilus structure in colonization of the human intestine by V. cholerae O1 and exemplify the significance of a genetic regulon in pathogenesis.

Adult↗
PubMed1999

Bacterial infections of the small intestine and colon.

Enterotoxigenic Escherichia coli, Vibrio cholerae O1, Campylobacter jejuni, Salmonella species, and Shigella species are major causes of morbidity and death in diarrheal disease. More recently recognized pathogens are V. cholerae O139 and enterohemorrhagic E. coli. In addition to this, several presumptive virulence factors have been identified in diarrheagenic E. coli and in other species. To confirm these as virulence factors we need good diagnostic tools and good epidemiological studies. These are of vital importance to create vaccines for diarrheal diseases.

Journal Article↗
PubMed2001

Bacterial infections: small intestine and colon.

Bacterial enteric infections exact a heavy toll on human populations, particularly among children. Despite the explosion of knowledge on the pathogenesis of enteric diseases experienced during the past decade, the number of diarrheal episodes and human deaths reported worldwide remains of apocalyptic dimensions. However, our better understanding of the pathogenic mechanisms involved in the onset of diarrhea is finally leading to preventive interventions, such as the development of enteric vaccines, that may have a significant impact on the magnitude of this human plague.

Journal Article↗
PubMed2003

Escherichia coli in infants' intestinal microflora: colonization rate, strain turnover, and virulence gene carriage.

Colonization by Escherichia. coli in infants might have decreased in the last decades, owing to changes in hospital routines and family lifestyle. In this study, the E. coli flora was characterized in 70 healthy Swedish infants followed for the first year of life. E. coli was isolated from rectal swabs obtained at 3 d of age and quantified in fecal samples collected at 1, 2, 4, and 8 wk of age and at 6 and 12 mo of age. Strains were typed using random amplified polymorphic DNA, and their virulence factor genes were identified by multiplex PCR. Colonization by E. coli occurred late; only 61% of the infants were positive by 2 mo of age. The turnover of individual strains in the microflora was slow (1.5 strains per infant during 6 mo, 2.1 during 1 y). Environmental factors, such as siblings, pets, or feeding mode, did not influence colonization kinetics or strain turnover rate. Genes encoding type 1 fimbriae, P fimbriae, and hemolysin were significantly more common in E. coli strains persisting for at least 3 wk in the microflora than in transient strains. The P-fimbrial class III adhesin gene was more common in E. coli from children who had a cat in their homes than in E. coli from children without pets (p = 0.01); this adhesin type is common in E. coli from cats. The late colonization and low E. coli strain turnover rate suggest limited exposure of Swedish infants to E. coli. Our results confirm that P fimbriae and other virulence factors facilitate persistence of E. coli in the human colonic microflora.

Animals↗
PubMed2000

Colon delivery efficiencies of intestinal pressure-controlled colon delivery capsules prepared by a coating machine in human subjects.

Large quantities of pressure-controlled colon delivery capsules (PCDCs) were prepared by a Hicoater-mini pharmaceutical coating machine and colon delivery efficiencies were evaluated in man. Caffeine powder as a model drug was suspended with a polyethylene glycol (PEG) 1000 suppository base at 50 degrees C, and was hardened in no. 0- and no. 2-sized capsular shapes. The capsule-shaped suppositories were coated with 5% w/v ethanolic ethylcellulose (7G grade) solution using the coating machine. By increasing the coating weight of ethylcellulose from 28.6 +/- 1.1 mg to 45.3 +/- 0.2 mg, the mean coating thickness of no. 0 PCDCs increased from 56 +/- 1 microm to 64 +/- 1 microm. With no. 2 PCDCs, the mean coating thickness increased from 50 micro +/- 1 microm to 57 +/- 1 microm by increasing the coating weight of ethylcellulose from 8.1 +/- 0.5 mg to 11.2 +/- 0.3 mg. The no. 0 PCDCs, having a mean ethylcellulose coating membrane thicknesses of 56 +/- 1 microm (type 1) and 64 +/- 1 microm (type 2), as well as no. 2 PCDCs, having thicknesses of 50 +/- 1 microm (type 3) and 57 +/- 1 microm (type 4), were used for in-vivo evaluation in man. After oral administration of test preparations containing 75 mg of caffeine, saliva samples were obtained and salivary caffeine levels were measured by an HPLC method. The first appearance time, Ti, of caffeine in the saliva was used as a parameter for the estimation of the release time of caffeine from PCDCs in the gastrointestinal tract. The mean Ti values of no. 0 PCDCs were 3.3 +/- 0.3 h for type- 1 and 5.3 +/- 0.3 h for type-2 preparations while the mean Ti values of no. 2 PCDCs were 4.3 +/- 0.5 h for type 3 and 5.3 +/- 0.3 h for type 4. There were good correlations between ethylcellulose coating membrane thicknesses and in-vivo Ti values. A colon arrival time of 5 h was reported in our subjects by gastrointestinal magnetomarkergraphy. PCDCs having a mean coating thickness of 64 +/- 1 microm for no. 0 capsules and of 57 +/- 1 microm for no. 2 capsules were thought to deliver caffeine to the human colon efficiently.

Adult↗
PubMed1991

[Simple and efficient cleansing of the large intestine for colonic radiography].

A clinical trial documented the excellent cleansing effect of a single low dose of the oral laxative sodium picosulphate. To achieve good preparation of the colon it is essential to ensure a combined regimen including simple diatary restrictions and liberal fluid intake during the two days preceding the radiological examination. An additional mechanical washout lavage is time-consuming and uncomfortable, and usually unnecessary for outpatients.

Administration, Oral↗