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Fiber, intestinal sterols, and colon cancer.

It has been postulated that dietary fiber's protective effect against the development of colon cancer, diverticular disease, and atherosclerosis may be due to the adsorption and/or dilution of intestinal sterols such as bile acids and neural sterols and their bacterial metabolites by component(s) of fiber. Dietary fiber is made up of four major components-cellulose, hemicellulose, lignin, and pectin. There is evidence that hemicellulose and pectin may induce an increase in fecal bile acid excretion in man which may be accompanied by a decrease in serum cholesterol. Natural fibers, such as rolled oats, alfalfa, guar gum, and Bengal gram have been shown to have hypocholesterolemic properties of alfalfa, wheat straw, and some other fibers found considerable amounts of bile acids in vitro. On the other hand, wheat bran, oat hulls, and all the synthetic fibers tested bound only negligible amounts of bile acids under the same conditions. Vegetarians in the United States have lower plasma lipids and different plasma lipoprotein patterns than those of comparable control populations on regular mixed diet. They also have smaller daily fractional turnover rates of cholic acid and deoxycholic acid pool size. In addition, populations on a mixed Western diet, where the rate of large bowel cancer is high (North American, English, Scottish, etc.) degraded and excreted cholesterol and bile acid metabolites to a greater degree than populations where the rate of colon cancer is comparatively low (Ugandan, Japanese, etc). It cannot be denied that the fiber theory linking fiber deficiency with the development of colon cancer and other diseases, is simple, attractive and appears to be firmly based in common sense. When subjected to research studies, however, the situation appears much more complex than expected. Although some progress is being made, the data are often contradictory and confusing, probably due to lack of adequate documentation of fiber intake (e.g., use of dietary fiber instead of crude fiber) and/or the absence of detailed information on the chemistry of the fiber itself.

Adult↗

Preliminary investigation of the probiotic potential of Lactobacillus rhamnosus strain GG in horses: fecal recovery following oral administration and safety.

This study was designed to evaluate whether Lactobacillus rhamnosus strain GG (LGG), an extensively studied probiotic organism in humans, can colonize the intestines of adult horses and foals. Lactobacillus rhamnosus strain GG was administered to adult horses at doses of 1 x 10(9) CFU/50kg bodyweight (BW)/day (group 1, 7 horses), 1 x 10(10) colony forming units/ 50kg BW/day (group 2, 7 horses) and 5 x 10(10) colony forming units/50kg BW/day (group 3, 7 horses) for 5 d. Foals received 2 x 10(10) colony forming units/50kg BW/day (group 1, 7 foals) or 1 x 10(11) colony forming units/50kg BW/day (group 2, 7 foals) for 5 d. Fecal levels of L. rhamnosus strain GG in adult horses were low and variable in the 2 lower dose groups. Even in the high dose group, colonization was relatively low. In contrast, more consistent intestinal colonization was present in foals, and colonization persisted for up to 9 d following cessation of administration. No adverse effects were observed in any animal. Clinical studies evaluating this probiotic are indicated in foals. The presence of this organism in the feces of adult horses may only represent passive movement through the intestinal tract, not actual colonization. Consistent intestinal colonization in adults was only achieved with a prohibitively high dose.

Administration, Oral↗

Colonic dendritic cells, intestinal inflammation, and T cell-mediated bone destruction are modulated by recombinant osteoprotegerin.

Autoimmune associated bone disease and intestinal inflammation are closely linked with deregulation and hyperactivation of autoreactive CD4 T cells. How these T cells are activated and mediate disease is not clear. Here we show that in the Interleukin 2-deficient mouse model of autoimmunity spontaneous osteopenia and colitis are caused by increased production of the ligand for receptor activator of NFkappaB (RANKL). RANKL acting via its receptor, receptor activator of NFkappaB (RANK), increases bone turnover and promotes intestinal dendritic cell (DC) survival in vivo. Modulation of RANKL-RANK interactions with exogenous recombinant osteoprotegerin (Fc-OPG) reverses skeletal abnormalities and reduces colitis by decreasing colonic DC numbers. This study identifies a common causal link between bone disease and intestinal inflammation and establishes the importance of DC in mediating colonic inflammation in vivo.

Adjuvants, Immunologic↗

Effect of preventive administration of a nonpathogenic Escherichia coli strain on the colonization of the intestine with microbial pathogens in newborn infants.

In a randomized, double-blind study, 27 healthy newborn infants were colonized with the nonpathogenic Escherichia coli strain Nissle 1917 (E. coli DSM 6601, Mutaflor) during the first 5 days of life by daily oral inoculation of 1 ml of a suspension with 10(8) living cells. A second group of 27 newborns, used as controls, received a placebo suspension (1 ml of phosphate-buffered saline) instead. Stool samples were taken on days 1, 2, 3, 5, and 21, and 6 months after birth. All samples were examined for the presence of the nonpathogenic E. coli strain and of pathogenic and potentially pathogenic microorganisms. The administered E: coli strain was detected in the stools of the colonized newborns from day 2 and remained present throughout the study in more than 90% of these infants. Colonization with true and potential bacterial pathogens was significantly reduced in infants receiving E. coli strain Nissle 1917 compared to the placebo group--both with respect to numbers of pathogens and to the spectrum of species.

Acinetobacter↗

[Segmental colonic stenosis in intestinal metastasis of breast carcinoma. A contribution to the differential diagnosis of colitis].

Four years after mastectomy for a scirrhous carcinoma a 71-year-old woman developed diarrhoea. Crohn's disease was suspected. At endoscopy a stenosis of the sigmoid colon was found which could not be passed: the mucosa was normal looking. Gastrointestinal radiography revealed segmental subtotal stenoses of the colon with linitis plastica, typical for tumour-caused infiltration, as well as indentations in the small intestine by mesenteric metastases. The diagnosis was confirmed by computed tomography and, finally, operation. Chemotherapy failed to produce any regression of the colon stenoses, and the patient died from mechanical ileus. In case of a similar history and colon stenoses of uncertain aetiology the possibility of intestinal metastases should be considered in the differential diagnosis.

Adenocarcinoma, Scirrhous↗

alpha-Lipoic acid ameliorates altered colonic contractility and intestinal transit in STZ-diabetic rats.

alpha-Lipoic acid treatment (100 mg/kg/day for 2 weeks after 6 weeks of untreated diabetes) of streptozotocin diabetic rats partially but significantly reversed both reduced contractile response of distal colon to acetylcholine and delayed transit of charcoal meal in small intestine compared to diabetic control. These effects of alpha-Lipoic acid were associated with complete reversal of diabetes induced increased plasma lipid peroxidation level. alpha-Lipoic acid had no effect on any of the parameters measured in non-diabetic rats. These findings demonstrate contribution of oxidative stress in the development of physiological changes of gut in diabetes.

Acetylcholine↗

Alterations in the colonic flora and intestinal permeability and evidence of immune activation in chronic constipation.

BACKGROUND: Disturbances in bowel function in chronic constipation could result in changes in the colonic flora and lead to disordered immunity and to decreased resistance to pathogenic flora. AIM: To investigate systemic immunity, the faecal flora and intestinal permeability in patients with chronic constipation, under basal conditions and following therapy with the laxative Bisacodyl. METHODS: Intestinal permeability, faecal flora analysis, T- and B-lymphocyte numbers, T-cell subpopulations, lymphocyte proliferation, phagocytosis, intracellular killing of Staphylococcus aureus by neutrophils, as well as circulating levels of immunoglobulins, immune complexes and antibacterial antibodies were assessed in 57 patients with functional constipation. In 12 patients with severely delayed transit, investigations were repeated following therapy with Bisacodyl. RESULTS: Ovalbumin concentrations, in serum, were higher in constipated patients (28.2+/-4.1 ng/ml versus 1.0+/-0.4 ng/ml, p < 0.05). Elevated counts of CD3+, CD4+, CD25+ cells, increased spontaneous proliferation of lymphocytes, elevated titres of antibodies to Escherichia coli and S. aureus, diminished counts of CD72+ B cells, diminished lymphocyte proliferation under phytohemagglutinin (PHA) stimulation and a diminished phagocytic index for both neutrophils and monocytes were found in the constipated patients. Concentrations of Bifidobacterium and Lactobacillus were significantly lower in constipated patients; potentially pathogenic bacteria and/or fungi were increased. Therapy with Bisacodyl resulted in normalisation of the faecal flora, a reduction in ovalbumin concentration and return towards normal for certain immunologic parameters. CONCLUSION: Constipation is associated with striking changes in the faecal flora, intestinal permeability and the systemic immune response. Relief of constipation tends to normalise these findings suggesting that these changes are secondary to, rather than a cause of, constipation.

Bifidobacterium↗

Induction of mineralocorticoid receptor by sodium butyrate in small intestinal (IEC6) and colonic (T84) epithelial cell lines.

Mineralocorticoid action is essential for colonic sodium and water absorption and is mediated via mineralocorticoid receptors in the upper half of colonic crypts. On the other hand, it has been established that sodium butyrate induces differentiation-like phenomenon in vitro. The aim of this study is to investigate whether this bacterial product participates in the regulation of gene and protein expression of mineralocorticoid receptor in vitro. IEC6 and T84 cells were stimulated by sodium butyrate and RNAs extracted. Gene expression of mineralocorticoid receptor was evaluated by northern blotting or semiquantitative RT-PCR. Protein expression was determined in T84 cells using immunohistochemistry. To investigate whether MR induction was associated with cellular differentiation, we also measured alkaline phosphatase in situ. The mineralocorticoid receptor gene was induced by sodium butyrate in both IEC6 and T84 cells. Immunoreactivity increased in butyrate-treated T84 cells, but receptor-containing cells were not uniformly distributed and often formed clusters. Induction of alkaline phosphate activity was also demonstrated in both IEC6 and T84 cells. Double staining by immunoreactivity and alkaline phosphatase activity clearly demonstrated the colocalization of both after butyrate treatment. In conclusion, sodium butyrate up-regulates gene and protein expression of the functionally important mineralocorticoid receptor in epithelial cells, after induction by differentiation-like condition in vitro.

Alkaline Phosphatase↗

Small intestine and small colon neuropathy in equine dysautonomia (grass sickness).

The number of neurons in the coeliacomesenteric ganglia and the myenteric and submucosal plexuses of the jejunum, ileum and small colon, and the pathological changes induced in them, were studied in various types of equine dysautonomia. In all forms of dysautonomia, severe and extensive neuron loss and damage occurred in the ileum. In acute and subacute dysautonomia, jejunal neuron loss and damage were severe, but in chronic cases significantly less loss or damage occurred. The damage followed the same pattern in the small colon but it was always less obvious than in the jejunum. The distribution of the damage was uniform within a segment of the intestine. In fatal cases of dysautonomia, the clinical severity and duration of illness seems, in most instances, to be related to the amount of neuronal disruption occurring in the jejunum. Severe disruption results in acute/subacute dysautonomia, while milder damage leads to the chronic form. No case of dysautonomia was encountered in which enteric neuron loss and damage occurred without significant neuronal disruption also occurring in the coeliacomesenteric ganglia. Heal neuronal damage and loss are not invariably worse than that in the jejunum, and the possible reasons for this, together with the relationship between neuronal damage and possible causes of dysautonomia, are discussed.

Animals↗

Toll-like receptor signaling in intestinal epithelial cells contributes to colonic homoeostasis.

PURPOSE OF REVIEW: Since intestinal epithelium expresses Toll-like receptors, it was suggested that the intestinal epithelium is actively involved in the maintenance of colonic homeostasis. Here we describe our recent findings, which support an active contribution of colonic epithelium to intestinal homeostasis via a unique activation of epithelial TLR9. RECENT FINDINGS: Recent data indicate that stimulation of Toll-like receptors by intestinal microbiota supports colonic homeostasis. Several Toll-like receptors are expressed in intestinal epithelium. TLR9, an intracellular protein in immune cells, is expressed on the cell surfaces of intestinal epithelium, both on the apical and the basolateral membrane. TLR9 signaling varies in a domain-specific manner; whereas JNK is activated by TLR9 ligand both apically or basolaterally, NF-kappaB is activated only via basolateral stimulation. In apical TLR9 stimulation, IkappaB is phosphorylated and ubiquitinated but is not degraded, and NF-kappaB-dependent inflammatory signals are not transduced. Stimulation of apical TLR9 compromises the inflammatory cascade induced basolaterally by several other Toll-like receptor ligands, suggesting that apical exposure to luminal microbial DNA restrains intestinal inflammation. SUMMARY: These data indicate that certain luminal bacterial products support colonic homeostasis via activation of epithelial Toll-like receptors. The role of epithelial Toll-like receptor expression and activation in the pathogenesis of human inflammatory bowel disease is yet to be explored.

Animals↗

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↗

Involvement of nitric oxide in nerve-mediated inhibition and action of vasoactive intestinal peptide in colonic smooth muscle.

Neurally mediated relaxation of canine colonic smooth muscle is associated with an increase in the resting membrane potential and is blocked by inhibition of nitric oxide synthesis. N omega-nitro-L-arginine completely prevented nerve-mediated relaxation, an effect that was reversed by L-arginine but not D-arginine. Vasoactive intestinal peptide (VIP) also relaxed canine colonic smooth muscle. Part of this relaxation was due to activation of inhibitory nerves and this effect was mediated by nitric oxide. In addition to the neurally mediated effect, VIP affected smooth muscle directly. This relaxation was associated with a reduction of the plateau phase of the slow-wave type action potential, without an effect on the resting membrane potential. This action of VIP was similar to that of forskolin which suggests that VIP increases intracellular cyclic AMP. In summary, nitric oxide mediates inhibitory innervation to smooth muscle as well as activation of inhibitory nerves by VIP. The electrophysiological mechanism by which VIP directly affects smooth muscle is described, an effect not mediated by nitric oxide.

Animals↗

Differential induction of major histocompatibility complex molecules on mouse intestine by bacterial colonization.

The aim of this study was to determine what factors induce major histocompatibility complex (MHC) molecules on the mouse small intestinal epithelium by using immunohistochemical methods. In germ-free mice, although MHC class I molecules such as H-2K and thymus leukemia antigen (TLa) were expressed on the small intestinal epithelium, class II molecules were absent. The introduction of microorganisms into germ-free mice induced characteristic MHC molecules on the small intestinal epithelial cells. The I-A molecule was induced on the villus tip and crypt epithelial cells 7 days after conventionalization, and the I-E molecule was induced on the mid villus and crypt epithelial cells 14 days after conventionalization. The staining intensity of the H-2K molecules was increased 4 days after conventionalization. In contrast, TLa did not change during conventionalization of germ-free mice. These results suggest that the expression of MHC molecules, except for the TLa, is greatly dependent on the presence of intestinal microorganisms.

Animals↗

[Angiodysplasias of the colon and small intestine: a not uncommon cause of gastrointestinal hemorrhage. 3 cases].

Three cases of bowel angiodysplasia with digestive bleeding were reported. In all cases, diagnosis was confirmed by arteriographic and/or histological data. Angiodysplasia of the colon was the most often an acquired and degenerative disease, and most commonly affecting patients after the seventh decade of life. This condition was a frequent and misinterpreted cause of bleeding per rectum in patients after fifty years. Selective superior mesenteric angiography, after colonoscopy (except during major bleeding) was the best investigation, showing pathognomonic images and specifing the site, often located in the caecum and/or ascending colon. Treatment was surgical, but endoscopic methods provided encouraging results.

Adult↗