Investigating the Whole Gut

Abstract

In this issue of the Journal, there is an interesting experimental investigation on oral rehydration solution (ORS) in thewhole gut with special reference to amylaseresistant starch (1). What is the meaning of the term ‘‘whole gut,’’ and how can we interpret the results of a whole-gut perfusion in rats? It is impossible to study an organ in a holistic sense as it does not function in isolation. For example, we are unable to examine an entity such as a single muscle, a pair of lungs or a complete liver without ‘‘interference’’ from adjacent organs. However, the intestine presents a particular case. It is a complex organ shaped like a tube with an entrance at one end and an exit at the other. Practical by design, a solution infused at point A can be collected at point B given any surplus. Therefore, it is feasible to study the whole gut at once. Why is this significant? One good reason is that ORSs have usually been studied using a segment of the intestine, often the jejunum, but thismethod excludes the colon in the testing of solution made to rehydrate children afflicted with diarrhea. The objective to reduce stool output through the colon, which is largely responsible for processingwater and electrolytes, has been without much consideration. That is, until now. By mentioning the whole intestine, the authors indicate the importance of colonic function. Technically, it is a difficult experiment that requires specific skills. They essentially found that amylaseresistant starch increases water and sodium absorption from iso-osmolar and reduced osmolar solutions. Rehydration is part of the daily activity of a pediatric center, and there is no question whether ORS rehydrates. Still, occasionally, oral rehydration therapy is not fully satisfactory; it could possibly aggravate the initial condition and may call for additional intravenous treatment. Furthermore, many mothers comment that oral rehydration does not treat the disease because it does not cure diarrhea. In response to such resistance and criticism, it is necessary to better understand the mechanisms of infectious diarrhea and how ORSs act on the whole intestine. This article will benefit readers of the Journal who wish to learn more about innovation and discovery within a well-researched topic. The treatment of diarrhea is as old as humanity itself, something like 100,000 years back, at least as old as the origin of art, 35,000 years ago. It is common to think that 30 to 40 years ago, the invention of ORS was a major breakthrough because it was based on firm pathophysiological knowledge. However, the efficacy of ORS was not proven by what we would now call a comparative clinical trial. The first studies were not blinded but performed by researchers with wide open eyes (2)! It was through 3 experimental results obtained on a segment of small intestine, which showed that water follows passively the absorption of actively transported sodium, glucose stimulates sodium chloride and water absorption, and cholera toxin does not alter those 2 physiological small intestine functions. Interestingly, these claims were derived from irreversible thermodynamic concepts, including the third law of thermodynamics (3). They were also checked by performing whole-intestine perfusions in adults with cholera (4). Jejunal infusion of an electrolyte solution comparable to watery stools did not reduce stool output, except with the addition of glucose. Does this mean that results from experiments done on a segment of small intestine could translate into applied therapeutic consequences? Unfortunately, several counterproductive examples from the past indicate otherwise. One of them is the relationship between jejunal lactase activity and lactose-induced diarrhea. Around the same time that ORS was invented, intestinal lactase was a main topic in the very new field of pediatric gastroenterology. It is hard to imagine now the excitement produced by the first measurements of disaccharidase activity on human jejunal capsule biopsies. It generated interesting scientific developments on persistent lactase activity after weaning in some human populations and on the environmental and genetic control of lactase activity. However, the findings also raised concern about lactose as a source of diarrhea. Low lactase activity on a jejunal biopsy was often considered equivalent to lactose malabsorption and lactose-induced diarrhea. During the 1960s and 1970s, breast milk was promoted as the reference food for infants. In this context, it came as a surprise that lactose Journal of Pediatric Gastroenterology and Nutrition 43:561–562 # November 2006 Lippincott Williams & Wilkins, Philadelphia