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Background: Diarrhea is a common problem in critically ill patients. Our patients are fed a high-carbohydrate enteral formula. We hypothesized that diarrhea in our patients may be related to the osmotic effects of unabsorbed carbohydrate in the small intestine and colon., Methods: We studied 19 patients, 3 months to 17 years, with burns >40% total body surface area. Each subject was studied weekly for up to 4 weeks postburn. Breath H2 concentration was measured. For the 24-hour period before the breath H2 measurement, the enteral carbohydrate intake, stool volume, and total enteral fluid volume were recorded. At each of several weekly intervals for each subject, the times when stool volume and enteral carbohydrate intake were each maximal were noted., Results: Maximal stool volume ranged from 12 to 69 mL/kg/d. At the time point of maximal carbohydrate intake, diarrhea (stool volume >10 mL/kg/d) occurred in 18 of 19 patients, and maximal stool volume occurred in 10 of 19. Breath H2 concentration (ppm/5% CO2; mean +/- SEM) was 5.5 +/- 3.5 at the time of maximal carbohydrate intake, and was 25 +/- 20 at maximal stool volume. There were no correlations among breath H2 concentration, stool volume, enteral fluid intake, and enteral carbohydrate intake., Conclusions: Almost all the subjects had diarrhea over several weeks postburn. The lack of correlation of either carbohydrate intake or breath H2 with stool volume suggests that diarrhea in these patients may be caused by factors other than carbohydrate malabsorption. These data do not support altering nutrition support because of watery diarrhea.

The purpose of this study was to determine whether doubling the lactose concentration in formula for preterm infants lowers the fraction of lactose digested and/or increases the fraction of lactose fermented. Six preterm infants, 31 to 36 weeks' postconceptional age, were fed a standard preterm formula (carbohydrate is 50% lactose and 50% glucose polymer)(SC) and/or the same volume of formula modified to contain lactose as the sole carbohydrate (LAC). Relative lactose digestion during the LAC formula feeding compared with SC formula feeding was measured by using a stable isotope approach for quantifying the fractional contribution of formula lactose to plasma glucose enrichment. Relative lactose digestion was 0.98 +/- 0.17 (range, 0.70 to 1.19). Fractional fermentation of lactose was estimated from breath H2 excretion (0.52 +/- 0.34 during LAC feeding and 0.23 +/- 0.22 during SC feeding, P = .11). The rate of breath H2 excretion was much higher with LAC (1.34 +/- 0.98 mL/h) than with SC (0.27 +/- 0.29, P = .029). In conclusion, doubling the lactose concentration had only modest effects on fractional lactose digestion. Increased breath H2 excretion with LAC may relate to fermentation of nonlactose sugar or to ill-defined changes in colonic physiology or motility, which could enhance colonic fermentation of malabsorbed sugar by H2-producing bacteria.

We have developed a system for chronically catheterizing 10- to 25-d-old pigs that permits stable isotope tracer studies of intestinal or colonic assimilation of nutrients. This model also can be used to ensure constant enteral feeding or to assess the rate of entry into the terminal ileum of carbohydrates, fats, and amino acids. A plastic cannula with a luminal flange can be surgically placed in the stomach for tracer studies of sugar digestion or for controlled infusion of any formula diet. A similar cannula can be placed in the cecum for infusion of tracer and(or) substrates for studies of fermentation. The cannula has been machined so that a washer and nut can be threaded onto it, allowing the entire apparatus to be fixed to the abdominal wall. The distal end protruding above the skin was tapered to fit standard i.v. extension tubing. A carotid arterial catheter was used to sample substrates for isotopic enrichment measurements.

In vitro studies of intestinal lactase activity and breath-hydrogen studies have suggested that the capacity for lactose digestion in preterm infants is less than the usual intake. To explore this question using an in vivo approach, we determined the fraction of dietary lactose hydrolyzed to glucose (and galactose) in 14 preterm infants with a gestational age of 26-31 wk at the time of birth but a postconceptional age of 31-37 wk at the time of study. The percentage of lactose digested was estimated after 6-h, primed, constant gastric infusions of [1-(13)C]glucose and D-[-1-(13)C]lactose on alternate days. A coefficient of lactose fermentation was derived from the rates of pulmonary excretion of hydrogen and carbon dioxide. Mean (+/- SD) lactose digestion was 79 +/- 26%. There was a significant inverse rank (r = -0.799, P < 0.01) and linear (r = -0.587, P < 0.05) correlation between this variable and postconceptional age. The percentage of lactose fermented averaged 35 +/- 27%.

In the newborn, sugars present in human milk and formulas are assimilated by both small intestinal digestion and, especially in the case of lactose, colonic bacterial fermentation. Colonic fermentation of carbohydrate serves three major functions: (1) conservation of a fraction of the metabolizable energy of dietary carbohydrate that is not absorbed in the small intestine; (2) prevention of osmotic diarrhea; and (3) production of short-chain fatty acids that stimulate sodium and water absorption, serve as fuel for colonocytes, and stimulate cell replication in colon and small intestine. Diarrhea produced in association with small bowel malabsorption of sugar may be caused by three, potentially overlapping mechanisms: (1) osmotic effects of unfermented sugar, which may cause secondary disruption of fermentation by purging the bacteria or diluting the bacteria mass; (2) damage to the colon mucosa from excessive fermentation leading to SCFA malabsorption and osmotic diarrhea on this basis; and (3) excessive fermentation leading to lowering of luminal pH and inhibition of bacterial enzymes. Therapy aimed at reducing diarrhea associated with sugar malabsorption might involve either slowing of motility to facilitate fermentation or stimulation of fermentative activity, but such interventions would depend on greater understanding of the mechanisms for colonic dysfunction in this condition.

It was hypothesized that low-molecular-weight products of carbohydrate fermentation would contribute only a small percentage to the total fecal excretion of nonfat, nonnitrogenous energy (carbohydrate energy) in premature infants. Infants born at 28-32 weeks' gestation who were 2-4 weeks of age were randomized to receive a formula with lactose as the sole carbohydrate (n = 7) or the same formula with 50% of the carbohydrate as glucose polymer (n = 8). The percent contribution (X +/- SD) to total carbohydrate energy of sugars (glucose, galactose, lactose, glucose polymer), short-chain fatty acids (acetate, propionate, butyrate, isobutyrate, valerate, and isovalerate), and D- and L-lactate was 9.4% +/- 2.9% for the 15 subjects and was not significantly different between groups. The percent contribution of all four sugars was 5.8% +/- 1.7% and did not differ between the two groups. Doubling the lactose intake resulted in significant increases in fecal excretion (kilocalories per kilogram per day) of acetate (77% increase; P = 0.03), total short-chain fatty acids (54%; P = 0.04), and galactose (188%; P = 0.03). These data suggest that as much as 90% of fecal carbohydrate energy may be in the form of large-molecular-weight compounds, presumably bacterial in origin.

Carbohydrate energy absorption and breath hydrogen concentration were measured in 12 premature infants 28-32 wk gestational age and 2-4 wk postnatal age. Each of two groups of six infants were randomly assigned to receive one of two formulas that differed only in carbohydrate source: 100% lactose (LAC) or 50% lactose: 50% glucose polymer (LAC + GP). In 11 infants the peak breath hydrogen concentration suggested extensive colonic fermentation (range 44-239 ppm/5% CO2 or 44-239 microL/L per 50 mL/L CO2). An approximate 100% increase in lactose intake in the LAC group was associated with a similar increase in breath hydrogen concentration at 30, 60, and 120 min. None of the infants exhibited diarrhea or vomiting or developed delayed gastric emptying. Carbohydrate energy absorption (mean +/- SD) was, respectively, 86 +/- 5% and 91 +/- 3% in the LAC and the LAC + GP groups (p greater than 0.05). Thus, colonic bacterial fermentation may be critical to energy balance and to the prevention of osmotic diarrhea in premature infants fed lactose.

A method was developed for assessing indirectly the fecal excretion of carbohydrate-derived energy. Then, eight healthy premature infants (28 to 32 wk gestation, postnatal age 12 to 30 days) were randomly assigned to receive one of two formulas that differed only in the carbohydrate source: 100% lactose or 50% lactose: 50% glucose polymer (lactose + glucose polymer). Excreta collections were analyzed for total nitrogen, urea nitrogen, ammonia, fat, and total energy. Carbohydrate energy absorption was calculated. The formulas were well tolerated and stool frequency, energy intake, weight gain, and nitrogen balance were not different in the two formula groups. Also, there were no significant intergroup (lactose versus lactose + glucose polymer) differences in the coefficients (%) (x +/- SD) of fat absorption (90 +/- 6 versus 93 +/- 5) or carbohydrate energy absorption (96 +/- 1 versus 95 +/- 3). Thus, net carbohydrate-energy absorption appeared normal in these premature infants who showed no clinical formula intolerance.

Newborn infants born after a term gestation appear to have an adequate capacity for small intestinal digestion and absorption of carbohydrate. Premature infants do not have a mature level of intestinal lactase activity. Apparently, in the premature infant, colonic fermentation serves an important, if not the only major route, for lactose carbon absorption, and it also appears that signs of fermentation activity such as increased BH2 are not indicative of disease. Important questions remaining in the premature infant relate to developmental aspects of colonic fermentative activity, effects of systemic antibiotic treatment on colonic salvage, the effects of various fermentation pathways on energy balance, the capacity for absorption of sugars, SCFA, and electrolytes by colonic epithelia, and the effects of fermentation products on metabolism and on the mucosal cells of the intestine or colon. Research addressing these questions may have relevance in the following areas: further development of formula diets for healthy premature infants and for patients of all ages with intestinal or colon dysfunction; the effects of colonic disease or surgical resection; the nutritional or clinical effects of dietary fiber; and the effects of antibiotic therapy on intestinal and colon function.