Eusorbents and eusorption: a review of physiological events to therapeutic concepts.

Eusorbents are considered the exogenous substances that facilitate and enhance intestinal absorption. Eusorption is the process by which eusorbents affect the mechanisms of intestinal absorption. These 2 concepts should be distinguished from the well-known probiotics and prebiotics that may also play a role in benefiting the host. This review covers the eusorption paradigm in the optimization of oral rehydration and the treatment of diarrhea. The various factors that influence the validity of eusorbents to facilitate the eusorption were considered (i.e., viscosity, hydrating agents, and minerals such as zinc). The role of surface tension in solute absorption was addressed. The possible effects that eusorbents could play in the gene activation of the intestinal mucosa were also considered. This review should contribute to the understanding of absorptive enhancements of specific substances and their properties that facilitate the desired effects in health and disease.

Modulation of rat intestinal nuclear factor NF-kappaB by gum arabic.

The objective of this study was to test the hypothesis that in an animal model of cathartic-induce intestinal dysfunction the proabsorptive effects of gum arabic (GA) could be associated with modulation of nuclear factor-kappaB (NF-kappaB) and with reduction of the inflammatory response caused by cathartics, as evidenced by intestinal mucosa cytokine production and gene expression. Juvenile male rats were given a phenolphthalein-magnesium citrate solution for 6 days, by itself or supplemented with either 10 or 20 g L(-1) GA, as a sole source of fluid. The controls given were tap water alone or with added 20 g L(-1) GA. The animals were euthanized and small-intestinal mucosa nuclear fractions and RNA were isolated. NF-kappaB p65 activity was highest after administration of cathartics, lowest in controls, and intermediate in GA-treated rats. Mucosal IL-1beta was overexpressed in tissues from cathartic-treated rats and from rats given high-GA solutions. Gene-array analysis revealed a complex pattern of gene regulation by cathartics which selectively upregulated several subfamilies of cytochrome P-450 family 2 genes. Co-administration of GA did not block this effect. These findings suggest that local anti-inflammatory effects on the small intestine could be obtained by administration of a nonabsorbable proteoglycan such as GA.

Enhancement of absorption by gum arabic in a model of gastrointestinal dysfunction.

OBJECTIVE: Diarrhea is a common and deadly threat to millions of infants and children. Similarly, malabsorption can aggravate the health status of the chronically sick and especially the elderly. Prompt recovery from intestinal dysfunction may have a substantial impact on many populations. The aim of this study was to test the hypothesis that, in an animal model of cathartic-induce diarrhea, the previously shown proabsorptive effects of gum arabic (GA) could directly reduce and ameliorate intestinal dysfunction. METHODS: Young male rats were offered a standard solid feed and as a sole source of fluid a phenolphthalein-magnesium citrate solution for 3 or 6 days (PC), or the same plus either 10 (GA1) or 20 (GA2) g/L of GA. Other groups had tap water without (CTL) or with 20 g/L GA (CTL + GA), after which the animals were jejunally perfused under anesthesia to test their absorptive capacity. Similarly treated rats were killed and the small intestinal mucosa scraped and processed for nitric oxide synthase (NOS) determination. RESULTS: In 6-day studies addition of GA to the cathartic solution led to increases in net water, sodium and glucose absorption with the higher GA2, relatively to the PC rats. For water (means +/- SEM): PC = 42.4 +/- 3.6; GA2 = 57.9 +/- 3.9 nmol/g.min, p < 0.05. For sodium: PC = 2,139 +/- 334; GA2 = 4,465 +/- 444 nmol/g.min, p < 0.05. After only 3-day exposure, effects were less marked. Total NOS activity was increased in the PC, GA1 and GA2 groups (333 +/- 26; 334 +/- 27; 336 +/- 23 nmol/h.g) compared to CTL (233 +/- 27 nmol/h.g, p < 0.05), while CTL + GA showed a further reduction of activity (190 +/- 18 nmol/h.g, p < 0.05 vs. CTL). CONCLUSIONS: These findings substantiate earlier physiologic and biochemical effects of GA on the gastrointestinal tract, presently conducted in a model of gastrointestinal dysfunction. The data further suggest that a natural proteoglycan such as GA can reduce secretory effects induced by cathartics and, hence, are predictive of potential effectiveness in the context of diarrhea or malabsorption by infectious or functional causes.

Meconium mineral content in small for gestational age neonates.

The mineral concentration of meconia of small for gestational age (SGA) newborns were compared with those of appropriate for gestational age (AGA) newborns of similar gestational ages (GA) to determine whether differences may provide clues of possible nutritional deficits of SGA infants, given that levels of meconium minerals could indicate the use of minerals by the fetus and the sufficiency of the maternal supply of minerals. Twenty-one SGA and 24 AGA newborns were included. Eleven SGA and 15 AGA were < or = 35 weeks GA. Ten SGA and nine AGA infants were > or = 36 weeks GA. All meconia from each neonate was processed and assayed for iron, zinc, copper, manganese, calcium, magnesium, and phosphorus. In the < or = 35-week subgroups, the SGA infants had lower meconium iron and manganese concentrations than that of the AGA. Among > or = 36-week newborns, SGA infants had a higher birthweight-adjusted copper concentration than AGA infants, but no differences were observed for the remaining elements. Lower iron and manganese meconium in < or = 35-week SGA infants may reflect either a greater use or a decreased maternal supply. The higher birthweight-adjusted meconium copper in the > or = 36-week SGA infants may be due to a comparatively reduced fetal use or increased maternal supply. These data may assist in clarifying potential mechanisms affecting intrauterine growth and/or potential nutrient deficits in the neonatal period.

Proabsorptive action of gum arabic in isotonic solutions orally administered to rats. II. Effects on solutes under normal and secretory conditions.

Gum arabic (GA) is a natural proteoglycan with proabsorptive capacity attributable to its physico-chemical properties. Previous experiments showed that in rats oral administration of GA in an isotonic solution had a generally positive effect. This study extends the investigation to include acetaminophen and to evaluate whether GA could also act under secretory conditions induced by theophylline. Test solutions were orally administered to rats under CO2 anesthesia and blood concentrations followed for 3 hr. The secretory effects of theophylline were clearly observed for sodium and zinc. Addition of GA resulted in a more rapid rate of glutamate absorption, under normal physiologic conditions, as indicated by the higher area under the curve (AUC). There were no differences in the presence of theophylline. Acetaminophen blood concentrations peaked about 30 min after administration, and the AUC in rats that received GA was higher than in those that got the solution without GA. AUCs for total body water distribution with time and those for glucose concentrations were indistinguishable whether the solutions contained or did not contain either GA or theophylline. The results confirm that oral administration of GA can accelerate absorption of some solutes, including pharmacologic agents.

Modulation of small intestinal nitric oxide synthase by gum arabic.

Preceding studies have revealed that gum arabic (GA), a natural proteoglycan (>/= 250,000 Da), has proabsorptive properties-as shown by increased sodium and water absorption-in normal rats, and especially in two animal models of diarrhea. Because nitric oxide (NO) metabolism is linked to gastrointestinal physiology, the goals of this study were to determine whether GA modulated NO and to determine intestinal function in vivo when NO production was enhanced by l-arginine (Arg), added at either 1 or 20 mM. Mechanistically, the goal was also to determine whether GA was a NO scavenger and a small intestinal NO synthase (NOS) inhibitor. Using a glucose-electrolyte solution in rat jejunal perfusions we found that GA at +/-10 microM (2.5 g/l) decreased nitrite and nitrate formation, tending to normalize water, sodium, and glucose absorption when modified by Arg addition. In vitro tests, with oxyhemoglobin as a marker, showed that GA at >/= 5 microM scavenged NO. For GA effects on NOS, small intestinal homogenate supernatants (10,000 g) from frozen tissues of either adult or 2-day-old rats were incubated for 1 hour at 37 degrees C in the presence of 2 mM Arg and increasing GA concentrations (0-100 microM). GA produced a concentration-dependent inhibition of NOS, reaching approximately 31% inhibition with 5 microM GA and up to 51% with 50 microM GA. GA at 100 microM produced no further inhibition. The data indicate that GA, in addition to its ability to remove NO diffused into the intestinal lumen, may also partially inhibit intestinal NOS and thus modulate intestinal absorption through these mechanisms. Use of GA as a food additive may help in restoring or improving small intestinal function in conditions where functional damage has occurred.

Proabsorptive effect of gum arabic in isotonic solutions orally administered to rats: effect on zinc and other solutes.

We have previously shown that the addition of gum arabic (GA) to oral rehydration solution (ORS) enhances water and electrolyte absorption during jejunal perfusion in rats under anesthesia. This study investigates whether GA by oral administration could be equally effective in rats. Isotonic solutions containing 25 g/L GA (AG), or without GA (A0) were administered via oral tube to lightly anesthetized adult female rats. Similar experiments were conducted with hypertonic solutions containing no GA (B0), or either 10 (B10) or 50 g/L GA (B50). Blood concentrations of sodium, glucose, glutamate, zinc, and tritiated water were determined at 0, 15, 30, 60, 90, 120, and 180 minutes, and results between treatments were compared. Administration of the isotonic, GA-containing solution (AG) resulted in a higher blood zinc level than with the isotonic GA-free solution (A0) from 15 minutes throughout 180 minutes. Blood zinc at 15 minutes (means +/- SEM) was as follows: for A0: 69.3 +/- 2.0, for AG: 83.4 +/- 3.5 nmol/L, P=0.002. At 180 minutes, A0: 52.6 +/- 1.8; AG: 68.1 +/- 4.6 nmol/L, P=0.004. The corresponding areas under the curve (AUC) were as follows: for A0: 10,737 +/- 214; for AG: 13,919 +/- 765 nmol x min/L, P<0.001). Glucose, glutamate, sodium, and tritiated water body distribution presented no differences in blood concentrations. For sodium and tritiated water body distribution, there was a significant time effect (P<0.0001). In hypertonic solutions, blood zinc levels declined over time, possibly due to their osmotic, counter-absorptive action, thus obscuring possible opposite effects of GA. GA appears to be an effective enhancer of zinc absorption when orally administered in isotonic solutions to laboratory animals. This proabsorptive capacity could be attributed to some of the physicochemical and biochemical properties of GA and suggest possible applications of GA in liquid formulas and solid food preparations.

Gum arabic (GA) modifies paracellular water and electrolyte transport in the small intestine.

Previous experiments have shown that a soluble fiber, gum arabic (GA), enhances water, electrolyte, and glucose absorption in animal models of diarrhea. The mechanisms implicated in this effect have not been fully elucidated. This study examined the possibility that paracellular transport is modulated by luminal GA, resulting in an enhanced rate of absorption in the small intestine. This hypothesis was tested by 3-hr jejunal perfusions on anesthetized rats with solutions containing 140 mM NaCl, 5 mM KCl, and 2 microCi/liter (74 kBq) 3H2O, with either 2.5 g/liter GA [+GA] or in its absence [CTL], and one of the following agents, capable of altering paracellular transport: chenodeoxycholic acid at 0.5 mM (CDC), 2,4,6-triaminopyrimidine (TAP) at 20 mM, and protamine at 100 mg/liter (PTM). Sodium, potassium, net water, and unidirectional water movement were measured. The addition of GA increased sodium absorption in perfusions with CDC, TAP, or PTM only. Similar effects by GA on net water absorption rates were obtained in tissues permeabilized with CDC and PTM; however, GA added to TAP did not normalize the reduction caused by TAP. Although PTM did not alter net water absorption, addition of GA to perfusates with PTM enhanced absorption values above those of CTL. GA reversed the strong negative effects of CDC on potassium absorption but was ineffective in this regard with TAP and PTM. The data obtained with those reagents that affect paracellular transport and the histological evidence support the view that GA promotes net absorption by this route in the small intestine of normal rats.

Cord blood red cell osmotic fragility: a comparison between preterm and full-term newborn infants.

BACKGROUND: The osmotic fragility of red blood cells reflects their membrane ability to maintain structural integrity. The osmolality at which the cells lyse is related to their shape, deformability, surface area/volume ratio and intrinsic membrane properties. In cord blood, there may be differences between premature and term infants, and be influenced by maternal medication and other factors. There have been no definitive findings on possible differences between preterm and full-term infant osmotic fragility. AIMS: To determine if cord blood erythrocyte osmotic fragility differs between premature and full-term newborn infants, using two parallel techniques. PATIENTS AND METHODS: Cord blood samples were obtained from preterm singletons (N=11), preterm multiple births (N=10), full-term infants (N=24), as well as adults (N=22), for comparison. An osmotic fragility test was used to determine the NaCl concentration at which 20%, 50% and 80% of hemolysis occurred using individual logistic curves. A glycerol lysis test determined the time needed to lyse 50% of red blood cells. RESULTS: Cord blood red cells of multiple birth premature infants were more hemolysis-resistant than erythrocytes from full-term infants or adults. Another index of osmotic fragility, the difference in NaCl concentration for 80% and 20% red cell hemolysis showed that premature infants had greater differences than full-term infants or adults. Glycerol lysis time revealed that both preterm and full-term infants had an erythrocyte subpopulation that took longer than adult blood to attain 50% hemolysis. Correlation between both tests was very significant (r=-0.603, P<0.0001, N=67). CONCLUSIONS: This study shows that erythrocytes of premature infants, although, in average, less osmotically fragile than those of healthy full-term infants, contain a more hemolysis-susceptible cell subpopulation.

Zinc as a potential enteroprotector in oral rehydration solutions: its role in nitric oxide metabolism.

Zinc has been recognized as an antioxidant with potential for chronic and acute effects. Oxidative damage produced by free radicals, including nitric oxide (NO), is responsible for certain types of intestinal malabsorption syndromes and diarrhea. Under physiologic or mildly stimulatory conditions for NO synthesis, the small intestine characteristically is in a proabsorptive state; however, an excessive production of NO triggers formation of cyclic nucleotides, which cause secretion and malabsorption. In this study, we hypothesized that low-molecular-weight, soluble zinc chelates could modulate the effects of induced NO excess on the small intestine. In vitro experiments demonstrated that zinc-citrate or zinc-histidine at > or =0.66 mM, as well as a known NO scavenger, 2-[carboxyphenyl]-4,4,4,4-tetramethylimidazoline-1-oxyl-3-oxide, at 2 microM, were effective at removing chemically generated NO. In vivo jejunal perfusions, conducted in healthy rats under anesthesia, showed that c-PTIO reduced the proabsorptive effects produced by 1 mM L-arginine, the precursor of NO. In a standard oral rehydration solution, 1 mM zinc-citrate partially reversed the antiabsorptive effects on potassium caused by an excess of NO generated from 20 mM L-arginine but did not alter sodium or water absorption. The data are consistent with the view that soluble zinc compounds incorporated into an oral rehydration solution may deserve further attention as a means to scavenge NO with fluids used for the treatment of chronic or acute diarrhea, especially in malnourished children who are often zinc deficient.

Neonatal outcome of infants born at 500 to 800 grams from 1990 through 1998 in a tertiary care center.

OBJECTIVE: To assess if there have been changes in survival, demographic data, obstetric features, neonatal morbidity, and short-term neurologic/radiographic/neurosensory outcome of 500- to 800-g infants born in a tertiary care neonatal center from 1990 through 1998. STUDY DESIGN: Records of all 500- to 800-g infants born at North Shore University Hospital during 1990-1998 were reviewed to determine demographic data, survival by weight and gestational age (GA), obstetric features, neonatal morbidity, and short-term neurologic/radiographic/neurosensory outcome. Newborn infants were grouped into three triennia: 1990-1992, 1993-1995, and 1996-1998 and compared across time. RESULTS: Of the 173 infants admitted to the neonatal intensive care unit, 112 survived. Improved survival was documented: 40% in 1990-1992, 73% in 1993-1995, and 81% in 1996-1998 (p < 0.0001). Improved survival was also noted in each of the three weight cohorts, as well as in infants < or =26 weeks GA. An increased use of antenatal corticosteroids and increased number of deliveries by cesarean section (C/S) were noted across time. The incidence of 0 to 3 Apgar scores at both 1 and 5 minutes decreased across time. Necrotizing enterocolitis in survivors and expected short-term neurologic/radiographic/neurosensory outcome improved between 1990-1992 and 1996-1998, with a trend toward reduced IVH grade III to IV. The incidence of other neonatal morbidities did not change throughout the time period. CONCLUSIONS: The data document that survival rates continued to improve for 500- to 800-g infants throughout the 1990s. This was concurrent with an increase in "low-risk, expected normal" infants, increased number of deliveries by C/S, decreased incidence of low Apgar scores at both 1 and 5 minutes, and an increased use of antenatal corticosteroids.

Effect of gestational age on cord blood plasma copper, zinc, magnesium and albumin.

BACKGROUND: The transport of essential trace elements from mother to fetus varies throughout gestation, and the role of transport proteins in the neonate and the mother may change during pregnancy. Magnesium, often used as tocolytic agent, may reach the fetus and appear in cord blood at higher than normal concentrations. AIMS: To determine cord blood plasma zinc, copper and magnesium concentrations, as well as plasma albumin in premature and full-term newborns, and correlate these values with those of maternal blood plasma at birth. Also, to examine whether cord blood plasma concentration of these elements varies with gestational age. SUBJECTS: The 35 mother-infant pairs included: 11 in the 38-42-week gestational age (GA), 9 in the 34-37-week GA, 11 in the 29-33-week GA group and 4 in the 24-28-week GA. Magnesium for tocolysis was given to five of the mothers in the 29-33-week GA cohort and two of the women giving birth at 24-28-week GA. RESULTS: Trend analysis showed that while cord plasma zinc decreased with GA at birth, the reverse was observed for copper. There were no differences with GA either in maternal plasma zinc or copper. However, maternal ceruloplasmin tended to decrease with GA (P=0.0174). Maternal and cord blood plasma magnesium exhibited a strong correlation (r=0.942, P<0.001), as well as between cord plasma magnesium and zinc (r=0.448, P<0.01). CONCLUSIONS: While the vigorous mother-to-fetus uphill zinc transfer is clear throughout the last trimester, copper remains in cord blood plasma at much lower concentrations than in the mother, suggesting that prematurity may place the newborn infant at a greater risk than the term infant to copper deficiency. This situation, together with a reduced synthesis in the fetus of the transport protein ceruloplasmin, creates another potential challenge in the nutritional support of the premature infant.

Regulation mechanisms of intestinal secretion: implications in nutrient absorption.

Intestinal secretion is a normal phenomenon, indispensible to solubilize and dilute nutrients and to maintain fluidity in the intestinal lumen. Enterotoxins and certain drugs may disrupt the proabsorptive status maintained by the small intestine under physiologic conditions. Hormones found in nervous and specialized intestinal enterochromaffin cells are responsible, in part, for secretion of fluid into the lumen. Afferent vagal nerve impulses mediated by 5-hydroxytryptamine (serotonin; 5-HT), vasoactive intestinal peptide (VIP) and substance P are the major agents of secretory stimulation. Toxins from pathogenic bacteria, especially some strains of E. coli and V. cholerae, trigger a secretory response and a chain of events involving cGMP and cAMP which result in chloride secretion, coupled to sodium and fluid efflux into the lumen. If secretion is unchecked by natural mechanisms or medications, the consequences are diarrhea, with potential dehydration, hyponatremia and ultimately death. Introduction of absorbable nutrients in the intestinal lumen has a major antisecretory action, both by a nutrient-gene interaction and by proabsorptive hormone expression. In additon, during the absorptive process water is carried into the enterocyte together with solutes. Hydrolysis-resistant peptides of dietary origin and ingested soluble fiber may also have a proabsorptive effect. The gastrointestinal system has a variety of antisecretory or proabsorptive hormonal and protein agonists that balance the outflow of fluid and electrolytes. The more extensively studied are neuropeptide Y/peptide YY (NPY/PYY) and the antisecretory factor (AF). Nitric oxide (NO), a short-lived second messenger, has a major role in secretion by activating cGMP. The intracellular concentration of NO may regulate the absorptive/secretory status of the small intestine, either stimulating absorption or inducing secretion. Specifically targeted 5-HT receptor antagonist drugs and other pharmacologic agents have been clinically tried for the treatment of severe diarrhea, drug-induced malabsorption and reversal of cellular damage.

Theophylline alters neutrophil function in preterm infants.

Theophylline (1,3-dimethylxanthine), which is often prescribed to premature infants to treat apnea, acts, in part, by altering the metabolism of cyclic AMP. This second messenger plays a role in signal transduction mediating neutrophil functions, including respiratory burst, chemotaxis, and motility. We hypothesize that theophylline causes reduced respiratory burst activity, chemotaxis, and random motility in neutrophils. In these studies, we aim at determining the effects of theophylline on neutrophil function in vitro in cells from preterm and full-term infants and adults as well as on neutrophils obtained from premature infants receiving theophylline treatment. Neutrophils were obtained from 20 preterm infants, 16 full-term infants, and 14 adults. Chemiluminescence, chemotaxis, and random motility were measured after exposure of these cells to theophylline in vitro (0- 84 micromol/l or 0-15 microg/ml). In addition, these neutrophil activities were correlated with serum theophylline levels in 13 preterm infants receiving theophylline treatment for 72 h. Neutrophils from premature infants, term infants, and adults all displayed reduced chemiluminescence, chemotaxis, and random motility at 84 micromol/l (15 microg/ml) of theophylline in vitro. The relative reductions were greatest in cells from premature infants (p < 0.01). A level-dependent reduction in these activities was also noted in neutrophils from preterm infants with serum theophylline levels >46 micromol/l (8.2 microg/ml; p < 0.001). In contrast, lower theophylline concentrations (about 28 micromol/l or 5 microg/ml), either in vitro or in vivo, caused significant increases in neutrophil activities. Theophylline concentrations in the high therapeutic range (84 micromol/l or 15 microg/ml) cause dose-dependent reductions in neutrophil chemiluminescence, chemotaxis, and random motility. Cells from preterm infants are particularly sensitive to this effect. In contrast, theophylline concentrations in the low therapeutic range (28 micromol/l or 5 microg/ml) cause increased neutrophil activities. Altered neutrophil activity in newborns related to theophylline treatment may affect the infants' response to infection as well as the incidence of inflammatory diseases.

Zinc supplementation in oral rehydration solutions: experimental assessment and mechanisms of action.

BACKGROUND: Zinc deficiency is associated with chronic diarrhea. This condition is generally linked to an overproduction of nitric oxide (NO), which induces secretion and cellular damage as a free radical. Use of oral rehydration solutions (ORS) is an important part of diarrhea treatment, especially early in infancy and for patients with cholera. The presence of zinc in an ORS could be a positive factor in recovery from diarrheal disease. OBJECTIVE: This study was undertaken to determine whether zinc added to an ORS could regulate the synthesis of NO metabolites in the lumen of zinc deficient rat intestine, acting as a gastrointestinal protector and thus accelerating normalization of intestinal function and zinc status. METHODS: The effects of zinc on NO metabolism were studied in young male rats fed a zinc deficient diet for three weeks to mimic the condition of patients with recurrent diarrheal episodes. During the fourth week of the zinc deficient feedings, experimental diarrhea was induced using cathartics (magnesium citrate plus phenolphthalein) that exacerbate NO production. A standard ORS with or without 1 mM zinc was given to the rats for the last two days. A control group received a zinc sufficient diet. Rats were killed at each stage. Intestinal nitric oxide synthase (NOS) was assayed, cecal fluid contents were analyzed for nitrates and nitrites, intestinal histology was examined, and activation of nuclear factor NF-kappaB DNA binding activity was determined. RESULTS: Rats fed the zinc-deficient diet for three weeks gained less weight than rats fed a normal zinc content diet and had a lower plasma zinc than controls (51.6 +/- 5.4 [n = 101 vs. 143.6 +/- 7.2 microg/dL [n = 11], p < 0.05). Recovery with ORS+Zn resulted in a higher plasma zinc than with the ORS-Zn (ORS+Zn: 186.5 +/- 12.2; ORS-Zn: 57.5 +/- 6.6 microg/dL, p < 0.05). The zinc-deficient diet did not alter mucosal NOS, as compared to the values of rats fed a normal diet. However, those animals which received five days of cathartic fluids had a small intestinal NOS higher than that of all other groups. Either ORS+Zn or ORS-Zn normalized NOS activity, regardless of cathartic treatment. The rats fed the zinc deficient diet had generally a higher content of NO metabolites in the cecum than rats fed a normal diet. After recovery with either type of ORS, rats given the cathartic remained with higher cecal NO metabolite concentrations than rats that had no induced diarrhea. After recovery with ORS+Zn, intestinal villi showed significant expansion of the lamina propria, an indication of greater absorption of fluid, while with ORS-Zn this was not present. Small intestinal homogenates of rats recovering with ORS+Zn had a decreased NF-kappaB DNA binding activity than tissues from rats consuming ORS-Zn. CONCLUSIONS: The results are consistent with the hypothesis that addition of Zn to an ORS may contribute to improving the physiologic status of the small intestine and potentially reduce the risks of recurrent diarrhea episodes.