Lectin ingestion : changes in mucin secretion and bacterial adhesion to intestinal tissue.

Phytohemagglutinin (PHA), the lectin derived from red kidney been (Phaseolus vulgarus) causes reduced growth rates in several animal species, when incorporated at 0.5-5% of dietary protein. Lectin feeding results in diarrhea, impaired nutrient absorption, growth rate inhibition, and can even lead to the eventual death of PHA-fed animals. These effects are believed to result from changes in the autochthonous microflora induced by the presence of PHA in the diet, as germ-free animals do not display the same changes seen in conventional animals (1-11) Jayne-Williams' (1,2) now classical studies in the quail clearly demonstrate this point. It is established that these adverse effects are the result of PHA-induced changes in the normal endogenous flora and are not due to lectin selection of specific pathogenic bacteria (9, 10) The major change appears in the levels of facultative aerobes, which increase in PHA-fed animals without an increase in obligate anaerobes (2,6). These observations separate the effects of PHA feeding from blind loop syndrome or other stressrelated changes in bacterial flora, in which anaerobic bacterial overgrowth is observed (12,13). Phytohemagglutinin feeding has also been observed to affect small intestinal growth (14).

Traveler's diarrhea.

A variety of infectious enteric pathogens (bacterial, viral, and protozoal) can lead to a systemic diarrheal illness in international travelers traveling from industrialized countries to developing areas of the world. Many of the agents that lead to this syndrome have been identified, and their mode of transmission has been defined. Prophylactic measures are advisable, and effective treatment options are available. This article also discusses issues important in the management of patients who develop a chronic diarrheal illness after travel.

Management of the neurogenic bowel in patients with spinal cord injury.

Bowel dysfunction in patients with spinal cord injury has a significant impact on quality of life as well as causing morbidity and death. This article reviews the pathophysiologic features of the neurogenic bowel of patients with spinal cord injury. Also discussed are the clinical manifestations, current options for management, and newer approaches that address this chronic and debilitating problem.

Small intestinal growth caused by feeding red kidney bean phytohemagglutinin lectin to rats.

BACKGROUND: Plant lectins are present in significant quantity in a variety of food sources. The aim of this study was to determine if they stimulated growth of the intestine. METHODS: Germ-free and conventional rats were pair fed purified phytohemagglutinin lectin (PHA) or equivalent casein in a fully nutritious diet. PHA was instilled into in situ jejunal and ileal loops. Organ weight, length, DNA, protein content, morphometry, and [3H]thymidine uptake into jejunal crypt cells were measured. RESULTS: A trophic response occurred in the small intestine (jejunum greater than ileum) because of PHA (P < 0.001), was sustained by continued exposure, and was reversible on reinstitution of the control diet (P < 0.05). The intestinal microbial flora in conventional animals that were fed PHA augmented the growth-stimulatory effects of PHA on intestinal weight (P < 0.01). PHA caused fecal protein, fat, and mucous glycoprotein levels (P < 0.001) to increase in germ-free animals. PHA increased jejunal mucosal crypt depth and crypt mitotic activity (P < 0.05); DNA content (P < 0.05) and [3H]thymidine uptake (P < 0.01) into crypt cells was increased. No increase in plasma or tissue content of gastrin, enteroglucagon, or peptide YY was observed on PHA exposure, and there was no increase in organ weight of the liver, kidney, or colon. CONCLUSIONS: PHA stimulated growth of rat small intestine when present in the diet or instilled in the bowel lumen.

Pyostomatitis vegetans and primary sclerosing cholangitis: markers of inflammatory bowel disease.

The case of a 34-year-old woman with both pyostomatitis vegetans and primary sclerosing cholangitis is reported and the literature reviewed. Pyostomatitis vegetans is a rare disorder characterized by friable pustules on the buccal mucosa and often peripheral blood eosinophilia. In this review, the frequent association of pyostomatitis vegetans with inflammatory bowel disease as well as the potential for pyostomatitis vegetans to present with sclerosing cholangitis and liver disease before any other manifestations of inflammatory bowel disease is discussed. Patients with pyostomatitis vegetans may need long-term care for gastroenterological disease in addition to treatment for oral lesions.

Worldwide impact of oral rehydration therapy.

Oral rehydration therapy (ORT) has had a dramatic global impact. The worldwide consequences of this therapy are discussed in four categories: (1) adoption of ORT as the primary therapy for acute dehydrating diarrhea; (2) establishment of national ORT programs; (3) scientific knowledge gained from studies into intestinal absorption of oral rehydration solutions; and (4) implications of ORT for the next decade. The Diarrheal Disease Control Program has been assigned a high priority by the World Health Organization. It now includes 99% of the population of the developing world, although it is not uniformly implemented. Because knowledge of how to use ORT parallels implementation, it is hoped that expanded training of community health workers will increase implementation. In addition, specific indications for ORT need further study and refinement so that community health workers may learn to distinguish between diarrheal episodes that require such therapy and those that do not. Better scientific understanding of intestinal absorption of ORT fluids has led to the development of new formulations that enhance absorption of nutrients and repletion of electrolytes. The optimal composition of such revised solutions has yet to be established. In addition to these improvements in utilization, distribution, education, and application of ORT, other measures to reduce the morbidity and mortality from diarrhea can be expected in the areas of better infant feeding practices, improved sanitation, management of persistent diarrhea, targeted therapy for particular groups of infants at high risk, and immunization.

PIP: The impact of oral rehydration therapy (ORT) on the estimated 5 million deaths of children yearly from acute dehydrating diarrhea is discussed in terms of worldwide adoption of ORT as primary therapy; establishment of national ORT programs; new scientific knowledge of intestinal absorption of ORT solutions; and implications of ORT for the next decade. ORT now encompasses 99% of the developing world, although it is implemented unevenly, as low as 12% in Africa. 75% of ORT formula is now produced locally. By 1988 60% of the world had ORT available, and 25% of affected children received ORT. More community health workers need training in ORT, since knowledge by mothers is key to treating children. Research is needed on the effect of ORT on aspiration pneumonia, the incidence of inadequate rehydration and death after ORT. Causes of death in children with diarrhea, and organisms associated with diarrhea resistant to ORT treatment. Current research focuses on maximal flow of nutrients and solvent drag across the intercellular tight junctions of the intestinal epithelium. Short chain fatty acids, butyrate, propionate and acetate, are also being studied as adjuncts to the carbohydrates and amino acids used in ORT solutions. In the future, ORT will be used with interventions such as breastfeeding, better weaning foods, sanitation, management of persistent diarrhea caused by specific organisms, targeted therapy and immunization.

Pathophysiology of diarrheal disorders.

Travelers' diarrhea is only mild or moderate in the majority of cases. Consequently, severe fluid and electrolyte losses are encountered only rarely. Secretory, osmotic, and inflammatory processes in the intestine result in increased losses of fluid and electrolytes due to diarrhea. Disorders of intestinal motor activity, coupled with fluid secretion, may also have a role in causing an increase in the frequency of bowel movements. Several systemic symptoms, such as malaise, fatigue, anorexia, nausea, and fever, are commonly associated with diarrhea and contribute to significant morbidity, which is often sufficient to compromise effective participation in a vacation or business trip. Several putative mechanisms for the systemic symptoms associated with travelers' diarrhea are discussed in light of recent understanding of the enteric nervous system, intestinal neuropeptides and hormones, and other inflammatory mediators released from the bowel wall during enteric infections.

Intestinal sphingolipid excretion associated with feeding of phytohemagglutinin lectin (Phaseolus vulgaris) to germ-free and conventional rats.

Intestinal sphingolipids of feces of germ-free and conventional rats were analyzed during the pair feeding of a complete defined diet containing phytohemagglutinin lectin (PHA) from red kidney beans (Phaseolus vulgaris) as 1% dietary protein in comparison to casein fed controls. Phytohemagglutinin in the diet increased the total fecal excretion of sphingomyelins (18-fold for germ-free and 20-fold for conventional rats), of non-acid glycosphingolipids (3.5-fold for germ-free and 9-fold for conventional rats) and also of the gangliosides (2.5-fold) for the germ-free rats compared to controls. For germ-free rats the increase of non-acid glycolipids was ascribed to an effect of the lectin strictly on the small intestinal mucosa, while for conventional rats an effect was seen also on the large intestinal mucosa. Increase of fecal gangliosides of germ-free rats was due mainly to an increased excretion of N-acetylneuraminosyl-lactosylceramide, a ganglioside species restricted to epithelial cells of duodenum, of upper jejunum and of large intestines. The effects on glycolipid excretion observed in germ-free rats and the rather similar effects seen in conventional animals suggested that the influence of dietary PHA was due directly to effects elicited by PHA binding to the enterocyte brush border membrane and not to secondary effects induced by increase in the luminal microflora.

Bacteria-lectin interactions in phytohemagglutinin-induced bacterial overgrowth of the small intestine.

The mechanism of phytohemagglutinin-induced bacterial overgrowth of the small bowel in the rat was studied. Interaction of the lectin with bacterial isolates selected at random from those that comprised the major population of the overgrowth was determined. In both bacterial agglutination assays and glycocalyx stabilization, no specific association between lectin and bacteria was seen. In three independent binding assays phytohemagglutinin was not found to increase bacterial adherence to washed intestinal mucosa. Phytohemagglutinin would not appear to act, therefore, as a direct ligand to mediate bacterial adherence or to modify the mucosal surface to increase bacterial adherence.

Bacterial overgrowth by indigenous microflora in the phytohemagglutinin-fed rat.

Phytohemagglutinin lectin (PHA) derived from red kidney bean (Phaseolus vulgaris) causes bacterial and protozoal colonization of the rat small intestine. To provide additional insights into this phenomenon we have studied the time course and population dynamics of microbial colonization of the major aerobe--facultative anaerobe groups which characterize this microflora. Compared with controls, PHA caused proliferation of a consistent adherent microbial flora in the jejunum (P less than 0.01). The predominant bacteria identified were Escherichia coli. a Streptococcal sp., and Lactobacillus. Escherichia coli isolates expressed no predominant serotype or fimbriae; none elaborated heat-labile or heat-stable toxin. Both E. coli and Streptococcal sp. populations increased within 24 h of PHA feeding and were sustained during further exposure to PHA (P less than 0.05). On reversion to a control diet, coliform counts fell progressively within 24-48 h and continued to decline, whereas gram-positive rod and coccus flora became the more prominent colonizers through days 1 to 4 of the reversion.

Nitrogen in fecal bacterial, fiber, and soluble fractions of patients with cirrhosis: effects of lactulose and lactulose plus neomycin.

To determine how lactulose and lactulose plus neomycin might alter nitrogen metabolism in the colon we investigated the effect of these agents on the distribution of nitrogen in the bacterial, soluble, and fiber fractions of stool. The alterations in fecal nitrogen excretion were additionally correlated with changes in total body urea synthesis and degradation rates. Six patients with stable cirrhosis received a control diet alone followed by the administration of lactulose (56 +/- 6 gm/day), and eight similar patients received lactulose alone (63 +/- 5 gm/day) followed by the addition of neomycin (4 gm/day). Their feces were partitioned into individual fractions by physical separation. Lactulose administration increased nitrogen excreted in the bacterial fraction by 165% (from 0.52 +/- 0.14 gm/day to 1.38 +/- 0.21 gm/day) and by 135% in the soluble fraction (from 0.58 +/- 0.08 gm/day to 1.36 +/- 0.23 gm/day). When lactulose was supplemented with neomycin, the nitrogen content of the bacterial fraction decreased by 28%. Lactulose caused a 23% reduction in the urea production rate that was mainly accounted for by increase in fecal nitrogen excretion. The addition of neomycin caused a further reduction in urea production that was explained by an inhibition of urea degradation. These results demonstrate that a major effect of lactulose was to augment the incorporation of nitrogen into fecal bacteria although nitrogen in the soluble fraction also increased. The additional nitrogen excreted in the fecal bacterial and soluble fractions caused a reduction in urea synthesis.

Intestinal water and electrolyte flux of glucose-polymer electrolyte solutions.

Carbohydrate-containing beverages, designed for consumption during physical activity, have been shown to improve endurance and performance during prolonged exercise. However, any solution consumed during exercise should allow rapid water absorption to ensure proper hydration. In this study, nine healthy volunteers were used to assess intestinal water and electrolyte flux characteristics of two carbohydrate-electrolyte solutions compared with water. One solution (GPF) contained 5.0% glucose polymers and 2.0% fructose, while the other (GPFS) contained 3.6% glucose polymers, 1.8% fructose, and 1.6% sucrose. Both solutions contained similar amounts of sodium, chloride, potassium, magnesium, and calcium (10, 10, 5, 1.2, and 3.2 mEq X l-1, respectively). Solutions were administered via a triple-lumen perfusion tube placed just distal to the ligament of Treitz in the small intestine. Polyethylene glycol (5 g X l-1) was employed as a non-absorbable marker to measure water and mineral fluxes. Results indicated that: jejunal intestinal net water absorption was similar for the GPF carbohydrate-mineral solution when compared with perfusion of plain water and replacement of a portion of the glucose-polymer with sucrose significantly slowed net water absorption when compared with perfusion of plain water. Net sodium, chloride, and potassium absorption also were not different for either of the two perfusates. These findings suggest that the water and mineral fluxes association with these solutions are not different from water alone. Therefore, the gastric emptying rate remains as the primary limiting factor in delivering water, carbohydrate, and minerals to the body.

Phytohemagglutinin from red kidney bean (Phaseolus vulgaris) inhibits sodium and chloride absorption in the rabbit ileum.

Phytohemagglutinin (PHA), derived from red kidney bean (Phaseolus vulgaris), can induce malabsorption and diarrhea when fed to rats. In this study, we determined the effect of PHA on ion transport in the rabbit ileum in vitro. Compared with control tissues, PHA (1 mg/ml) added to the mucosal solution increased short-circuit current (1.1 +/- 0.2 microEq/cm2 X h, p less than 0.001), decreased net Na (-1.0 +/- 0.5 microEq/cm2 X h, p less than 0.02) and Cl (-1.2 +/- 0.6 microEq/cm2 X h, p less than 0.025) absorption, and decreased tissue conductance (-1.8 +/- 0.5 mS/cm2, p less than 0.001). Serosal addition of PHA had no effect on the short-circuit current or tissue conductance. Mucosal PHA did not increase mucosal levels of cyclic adenosine monophosphate or cyclic guanosine monophosphate. Removal of serosal calcium did not affect the increase in short-circuit current induced by mucosal PHA. Utilizing fluorescent microscopy, rhodamine-labeled PHA was found to bind to the luminal border of villus cells, but not to crypt cells, in the ileum. In the descending rabbit colon, PHA did not affect either the short-circuit current or conductance, and rhodaminated PHA did not bind to the epithelial surface. Using the increase in short-circuit current as an indicator of absorption, PHA did not affect Na-coupled glucose or amino acid absorption in the ileum. This study suggests that dietary lectins may play a role in regulating intestinal fluid and electrolyte transport.

Treatment of travelers' diarrhea: fluid and dietary management.

Travelers' diarrhea is associated with a mild or moderately severe loss of fluid and electrolytes. Severe fluid deficits are encountered only rarely. Mortality associated with fluid deficits is very rare; significant morbidity occurs only in older adults or in patients with chronic intestinal diseases or other chronic diseases (cardiac, pulmonary, or renal). Treatment of fluid and electrolyte deficits may be effectively achieved by rehydration with oral rehydration solution (World Health Organization) or with a commercial solution of similar composition. Dietary recommendations should emphasize the necessity of resuming a normal diet once a reduction in symptoms makes this feasible. Eating small portions frequently and omitting caffeine and lactose-containing food and drink may be advantageous.

Binding of isolectins from red kidney bean (Phaseolus vulgaris) to purified rat brush-border membranes.

Ingestion of red kidney bean phytohemagglutinin causes impaired growth and intestinal malabsorption, and facilitates bacterial colonization in the small intestine of weanling rats. We have studied interactions of the highly purified phytohemagglutinin erythroagglutinating (E4) and mitogenic (L4) isolectins with microvillous membrane vesicles prepared from rat small intestines. E4 and L4 were radioiodinated with 125I by the chloramine-T technique. E4 and L4 isolectins both bound to microvillous membrane vesicles. Binding was saturable and reversible. Each mg of membrane protein bound 744 +/- 86 micrograms E4 and 213 +/- 21 micrograms L4. The apparent Ka for E4 and L4 binding was 2.5 x 10(-6) and 13.0 x 10(-6) M-1, respectively. Binding of each 125I-labelled isolectin was abolished by 100-fold excess of unlabelled isolectin. In each case binding also was inhibited by appropriate oligosaccharide inhibitors, indicating that isolectin-microvillous membrane interactions were mediated by carbohydrate recognition. Patterns of saccharide inhibition of isolectin binding were different for E4 and L4. Competitive binding experiments demonstrated mutual noncompetitive inhibition of E4 and L4 binding consistent with steric hindrance. Therefore, E4 and L4 each bound to its own set of receptors. Based on the known saccharide specificities of E4 and L4, these data indicate that there are differences in expression of complex asparagine-linked biantennary and tri- or tetraantennary oligosaccharides at the microvillous surface. The data also provide the possibility that direct interactions of one or more phytohemagglutinin isolectins with intestinal mucosa in vivo may contribute to the antinutritional effects associated with ingestion of crude red kidney beans.

Effects of vegetable diets on nitrogen metabolism in cirrhotic subjects.

This study compared the effect of a vegetable diet with an animal protein diet on various aspects of nitrogen metabolism to identify what components of the vegetable diet might be causing beneficial therapeutic effects in hepatic encephalopathy. Vegetable diets contained 4.5-fold greater amounts of fiber (56 +/- 3 g/day) and reduced amounts of methionine, tyrosine, and tryptophan. In 6 stable cirrhotic subjects without encephalopathy, vegetable diets caused a significant reduction in the urea production rate from 106 +/- 5 to 89 +/- 5 mg X kg-1 X 24 h-1 of urea nitrogen. This was mainly accounted for by a fall in urinary urea output. Vegetable diets also caused a fall in total urinary nitrogen, which was accounted for by the fall in urea nitrogen, and a comparable increase in fecal nitrogen from 12 +/- 2 to 28 +/- 5 mg X kg-1 X 24 h-1. The fecal bacterial fraction contained 63% of the increase in stool nitrogen. Most plasma amino acids, including methionine, tyrosine, phenylalanine, as well as total and free tryptophan, were unchanged. The effect of vegetable diets on nitrogen metabolism can be mainly accounted for by the increased intake of dietary fiber and increased incorporation and elimination of nitrogen in fecal bacteria.

Intestinal microbial flora after feeding phytohemagglutinin lectins (Phaseolus vulgaris) to rats.

Incorporation of purified phytohemagglutinin (PHA) lectins derived from red kidney beans (Phaseolus vulgaris) in the diet of weanling rats will cause growth failure, malabsorption of nutrients, and bacterial overgrowth in the small intestine. These effects are not caused by feeding a similar quantity of PHA to germfree rats. To define the morphological and bacterial changes on the mucosal surfaces of the jejunum, ileum, and cecum in greater detail, we pair fed two groups of weanling rats isocaloric, isonitrogenous diets with or without 0.5% PHA protein. On the jejunal surfaces of control rats, the mucous layer was a confluent covering with sparsely scattered bacteria and protozoa. In PHA-treated rats, the mucous layer was thin and discontinuous, and the microvillous surface of the tissue was extensively populated by bacterial cells of two distinct morphotypes--a gram-negative rod and a gram-positive coccobacillus. In all PHA-treated animals, these bacteria formed adherent monospecific or mixed adherent microcolonies on the tissue surface. Tissue damage was observed in PHA-exposed jejunal tissue as evidenced by vesiculation of the microvillous plasma membrane and by damage to the brush border membrane. On the ileal surfaces of control rats, there was a thick mucous layer within which small numbers of bacteria and protozoa were seen. Segmented filamentous bacteria were anchored in the tissue surface. In PHA-treated rats, the ileal surface was only incompletely covered by a mucous layer, and the overlying mucosal surface was extensively covered by large numbers of protozoan cells (predominantly Hexamita muris). Most of the ileal surfaces not covered by the mucous layer were occupied and virtually occluded by an overgrowth of these protozoan cells with occasional cells of Giardia muris and the tissue-associated segmented bacillus. In the ceca of control rats, the mucosa was incompletely covered by a discontinuous mucous layer and colonized by an unnamed Spirillum sp., other bacteria, and occasional protozoa. The cecal surfaces of PHA-treated rats retained most of their incomplete overlying mucous layer, which was heavily colonized by the same type of Spirillum sp. seen in untreated animals; intestinal crypts were colonized. These descriptive morphological studies demonstrate that exposure to purified PHA in the diet caused characteristic changes in the microbial ecology of the small intestine. The changes in microbial flora contributed to the malabsorption of nutrients in the small intestines of PHA-fed animals.

Phytohemagglutinin-induced diarrheal disease.

A purified plant lectin, phytohemagglutinin (PHA), or crude red kidney bean (RKB) from which it was derived, when incorporated as 1% of dietary protein into a purified casein protein diet caused weanling rats to fail to grow or lose weight in comparison to control animals pair fed an isonitrogenous, isocaloric diet. Feeding PHA was observed to cause diarrhea: fecal wet and dry weights were increased within 2 days after starting the diet. Increased fecal weight was caused by increased dry weight as well as by an increased fecal water content. On reversion to a normal casein diet, rapid amelioration of the antinutritional effects of PHA occurred with resumption of normal growth rate. Specific binding of PHA to the microvillus region of the small intestinal epithelium was demonstrated using rabbit anti-PHA and fluorescein-labeled goat anti-rabbit immunoglobin. PHA binding was observed after chronic intake in the diet or when applied to normal tissue in vitro. Loss of PHA binding to the intestine was observed to occur within 48 hr on reversion to a control casein diet. No significant morphological damage to the microvilli or the mucosal villus architecture was observed to accompany PHA adherence under these experimental conditions. Antinutritional and antiabsorptive effects of dietary PHA were associated with diarrhea. PHA adhered to the microvillus membrane of the small intestinal villus surface during the diarrheal state.(ABSTRACT TRUNCATED AT 250 WORDS)

Intestinal and pulmonary cryptosporidiosis in an infant with severe combined immune deficiency.

Small intestinal biopsy established the diagnosis of cryptosporidiosis in a 6-month-old male infant with severe combined immune deficiency. Scanning and transmission electron microscopy revealed the ultrastructural details of Cryptosporidium in several stages of development within the patient's small intestine. The organism was resistant to all antibiotics used, and the patient died in the 5th month of his illness, despite receiving parenteral alimentation and undergoing thymus transplantation. His clinical course was similar to that of other patients with fatal immune deficiencies and cryptosporidiosis. Autopsy demonstrated organisms attacking the epithelium of the small intestine, pancreatic duct, and bronchioles. Multiple organ involvement in this patient negates the view that Cryptosporidium is site-specific for a given host or is alimentary-canal-specific in humans.

Phytohemagglutinin derived from red kidney bean (Phaseolus vulgaris): a cause for intestinal malabsorption associated with bacterial overgrowth in the rat.

Plant lectins or carbohydrate binding proteins interact with membrane receptors on cellular surfaces but their antinutritional effects are poorly defined. Studies were conducted to determine the effects of phytohemagglutinin, a lectin derived from raw red kidney bean (Phaseolus vulgaris), on small intestinal absorptive function and morphology, and on the intestinal microflora. Phytohemagglutinin was isolated in purified form by thyroglobulin-sepharose 4B affinity chromatography. Red kidney bean and phytohemagglutinin (6% and 0.5%, respectively, of dietary protein) were fed in a purified casein diet to weanling rats for up to 21 days. Weight loss, associated with malabsorption of lipid, nitrogen, and vitamin B12, developed in comparison with animals pair-fed isonitrogenous casein diets. Antinutritional effects of red kidney bean were reversible on reinstitution of a purified casein diet. An increase in bacterial colonization of the jejunum and ileum occurred in red kidney bean- and phytohemagglutin-fed animals. When antibiotics were included in the diet, malabsorption of [3H]triolein and 57Co-vitamin B12 in red kidney bean-fed animals was partially reversed and, in germ-free animals, purified phytohemagglutinin had no demonstrable antinutritional effect. Mucosal disaccharidase activity was reduced in red kidney bean- and phytohemagglutinin-fed animals, but intestinal mucosal morphology was unchanged. Dietary administration of phytohemagglutinin, alone or as a component of red kidney bean, caused intestinal dysfunction, which was associated with, and dependent upon, small intestinal bacterial overgrowth. Adherence of enteric bacteria to the mucosal surface was enhanced by phytohemagglutinin which may have facilitated small intestinal bacterial overgrowth.