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Fibre and enteral nutrition
ClinicalNutrition (1993) 12 tSuppl, 1): 5106-5113 © Longman Group UKLtd 1993
Fibre and enteral nutrition D.S.A. SILK Department of Gastroenterology and Nutrition, Central Middlesex Hospital NHS Trust, Acton Lane, London NW10 7NS, UK
Introduction Clinical experience during the last decade has confinned that enteral nutrition is an efficient and cost effective means of providing nutritional support to patients with normal or near normal gastro-intestinal function (1). Before and during this period the knowledge gained of the processes involved in the physiology of nutrient absorption has been applied to the formulation of enteral diets; and if comparisons are made of the composition of present day diets with those used 10-15 years ago several differences can be seen. These relate mainly to the nitrogen and energy concentrations of polymeric diets, and the sources of nitrogen and energy and electrolyte compositions of predigested chemically defined elemental diets (2). Until recently all the commercially produced liquid enteral diets continued to have one thing in common, namely that they contained a low residue or low 'fibre' content. The very earliest low residue enteral diets were specifically designed not only to provide balanced nutrition to astronauts in space, but also to reduce their stool weight and stool frequency (3). Subsequently it was realised that one clinical advantage of low residue diets was that they had a low viscosity and could be administered easily through 'fine bore' nasogastric or nasoenteric feeding tubes. Furthermore as it became clear that there could even be a number of therapeutic advantages in administering low residue diets (4) their widespread use became accepted without question. Although the 1970s and early 1980s has been the time when advances have been achieved in the field of enteral nutrition the same period has seen also significant advances in the field of fibre research and as a consequence there has developed a belief that many of the diseases of western civilisation such as atherosclerosis, obesity, appendicitis, constipation, irritable bowel syndrome, colon cancer, diverticular disease, diabetes mellitus and gallstones were related to a deficiency in dietary fibre, and that supplementing the diet with fibre would prevent and might even cure these conditions (5). Although not all recent studies (6) have been in complete agreement the observations 106
made by Heaton and colleagues over 10 years ago (7, 8) that ingestion of bran accelerated slow intestinal transit and delayed rapid intestinal transit, lead to suggestions that the ingestion of fibre produces a more regular bowel habit (9). Based largely on the above premise as well as on the fashionable doctrine that dietary fibre was good overall, suggestions began to be made in the second half of the 1980s that there could be benefits to supplementing commercially produced liquid enteral diets with fibre. In 1989, our Unit published the first major review on fibre and enteral nutrition (10). Attempts were made to critically examine the premises on which the proposed use of fibre supplemented enteral diets were based. The definition of dietary fibre was discussed (11), the physiology of dietary fibre assimilation reviewed and particular attention was paid to discussing the factors affecting the breakdown of non starch polysaccharide (NSP) in man. Of importance in relationship to the clinical applications of fibre supplementation in enteral feeding was the fact that non-cellulosic polysaccharide (NCP) components of dietary fibre are known to be degraded more efficiently than cellulose (11). The influence of important physical properties such as solubility (12), particle size (13) and surface area (14, 15) on the degree of digestibility was emphasised as was the influence that the substrate inducibility of the colonic bacterial polysaccharidase enzyme systems would likely to exert on fibre degradation (16). As a consequence of these discussions it was suggested that the physical characteristics of the fibre sources being used clinically in enteral feeding were likely to rapidly degrade, not only because most were predominantly NCP, but because particle size was small (in order to overcome viscosity problems), and since only single fibre sources were being employed, digestibility would increase with time, a situation which was envisaged during long term administration of fibre supplemented enteral diets (10). Two main areas of interest in fibre and enteral nutrition were identified, namely effect on bowel function and effects on small and large intestinal mucosal
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cell morphology (16). A particular area of interest that developed later, concerned with the effects of fibre supplementation on mucosal barrier function has arisen. This article seeks to update progress that has been made in these areas. Fibre and enteral nutrition - effect on bowel function
Constipation Studies of healthy volunteers have shown that the majority of the population in the Western World pass one bowel movement per day with an average daily output 120-130 g stool (17). Similar findings were reported in normal subjects taking part in dietary studies and consuming metabolically controlled diets (18). Large individual variation is seen, however, both in frequency and weight of bowel movements, without complaints of either constipation or diarrhoea (19). Such variability in normal bowel habit makes it difficult to define an abnormal or constipated state and to date this basic difficulty has not been overcome (19). Clinical studies in which fibre free defined formula enteral diets have been administered to normal healthy volunteers suggest that wet stool weights in the range of 40-70 g/d in the norm with a daily stool frequency of 0.5-0.7 (20-23). Based on the known effects that increasing the intake of dietary fibre has on bowel function (10) most investigations have sought to show that supplementing fibre free enteral diets with fibre results in increases in daily stool wet weights and transit time. Certainly these have been the main goals of investigators who have carried out studies in normal healthy subjects as well as in stable medical patients and those with psychiatric or neurological disorders. Although Slavin and colleagues (20) showed that the addition of 30 and 60 gld soy fibre to a fibre free defined formula diet administered to normal healthy volunteers resulted in significant increases in daily wet stool weight (60 g/d) and daily stool frequency the findings of other studies carried out in normal healthy volunteers have been less impressive (21). Direct comparisons of data are unwarranted however, as experimental designs have not been standardised. In our Unit, we have been interested in investigating the differential effects of readily metabolised and relatively poorly metabolised fibre sources on bowel function of normal human volunteers fed fibre free and fibre supplemented diets (24, 25). Positive effects have been minimal even where a poorly metabolised oat fibre source was studied (26).
One interesting recent study (27) has shown that the administration of a fibre free chemically defined elemental diet to normal human volunteers resulted in the passage of liquid stools in 60% of subjects. The addition of pectin (range 14.5-31.5 gld) abolished the liquid stools (27). Two controlled studies have been performed in stable medical patients (23, 28). Neither the addition of 24 gld carrot fibre nor 12.4 gld and 38.5 g/d of soy polysaccharide fibre to fibre free liquid formulae resulted in any significant change in the parameters of bowel function studied. In a prospective crossover study performed in 28 mentally retarded young individuals suffering from chronic constipation as a consequence of fibre free enteral feeding, the addition of soy polysaccharide (15.6-17.4 g/d) for 2 weeks was without effect on stool weight, stool frequency or transit time (22). In a subsequent study from the same Unit (29) a 1 year trial in 11 mentally retarded patients showed that supplementation of a fibre free liquid diet administered via gastrostomy with 18-25 gld soy fibre resulted in a significant increase in stool weights (30 ± SD 13 g/d vs 87 ± g/d) and bowel frequency 0.6 ± 0.2 vs 1.1 ± 0.5). One final study carried out in patients with neurological disorders (30) is difficult to interpret as the mean wet stool weights in the patients receiving long term tube feeding with a fibre free diet were much higher (142.6 g/d) than one would have expected. The requirements of laxatives were reported to be significantly less when the patients received the same diet supplemented with 12.8 gIL soy fibre. One is forced to conclude as a consequence of the above studies that the supplementation of fibre free defined formula diets with a single fibre source results in only marginal benefits in respect of bowel function and that the positive benefits shown are of questionable clinical significance. Rapidly degraded fibre sources increase faecal weight by virtue of the fact that they stimulate growth of microflora within the colon (31, 32). Poorly digested fibre on the other hand, stimulates bacterial growth to a lesser degree, but survives to hold water (33). Poorly degraded fibre produces larger faecal weights than equivalent supplements of more rapidly degraded fibre (19, 31). It is perhaps hardly surprising therefore that the studies described above, most of which have employed the use of well degradable small particle sized single sources of predominantly non cellulosic polysaccharide containing fibre, have produced such modest improvements in bowel function. If in the future, there remains a demand to improve bowel function in patients receiving long term enteral feeding then a different strategy will be required.
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FIBRE AND ENTERAL NUTRITION
Possibilities would seem to include the use of multiple fibre sources that in tum should be varied to overcome the problem of substrate inducibility of the colonic bacterial polysaccharidase enzyme systems (16). Consideration might be given to the use of more poorly degraded fibre sources. Caution is required though as the oat fibre studied by our group (26) was without effect on bowel function, and the use of cellulose as a fibre supplement resulted in the production of hard pellety stools that were painfully difficult to pass (34). Much innovative thinking and research will be required before the problems of sluggish bowel function and low stool weights in patients on long term enteral feeding are overcome.
Diarrhoea Diarrhoea is a significant problem in enteral nutrition. According to basic physiological principles, which take into account the capacity of the normal small and large intestine to assimilate fluid and electrolytes, diarrhoea can be defined as the passage of more than 200 g of stool/24 h on an average Western diet (35). It follows that the diagnosis of diarrhoea is dependent on accurate measurements of stool outputs, hardly a feasible proposition in uncooperative enterally fed patients with faecal incontinence. For the purposes of our clinical studies we have therefore defined enteral feeding related diarrhoea as the passage of too frequent stools or stools of too loose a consistency that are of inconvenience to the nursing staff and/or the patient (36, 37). In our original experience, diarrhoea so defined, occurred in up to 25% of patients receiving enteral nutrition (38). A number of factors have been implicated in its pathogenesis (1). These include use of infected feeds, lactose intolerance, intolerance of high osmotic loads of nutrients administered, inappropriate release of gastro-intestinal polypeptide hormones, concomitant antibiotic therapy, ingestion of laxatives, and hypoalbuminaemia. The role of lactose intolerance in the pathogenesis of the diarrhoea has been discussed in some detail (1). In brief, the deleterious effect of lactose in enterally fed patients with lactose intolerance will depend on the load (concentration x rate) of lactose administered. Bolus feeding in lactose intolerant patients results in the production of stool volumes in excess of 1 1/24 h (39). In contrast, when a low load of lactose is presented to the upper small intestine, as occurs during constant 24-h intragastric infusion of liquid lactose containing diets, diarrhoea does not occur (36). In a prospective controlled trial of continuous 24-h nasogastric infusion of polymeric diets to patients with normal or near normal gastro-intestinal
function, the development of diarrhoea was not related to osmotic load of nutrients presented for absorption but to concomitant antibiotic therapy (37) an abservation that has subsequently been confirmed (40,41). Animal studies carried out in our laboratory have not confirmed that the onset of diarrhoea is related to an inappropriate release of gastro-intestinal polypeptide hormones (42). Finally, hypoalbuminaemia has been related to the development of diarrhoea (43). Disappointed that so little progress was being made in achieving a greater understanding of the pathogenesis of enteral feeding related diarrhoea, we have undertaken a series of intubation studies in normal human subjects receiving continuous intragastric or intraduodenal enteral feeding. For the first series of experiments we devised and validated a multilumen orocaecal intubation technique that has permitted the study of small intestinal motility responses to the enteral feeding as well as permitting quantitative of colonic inflows of nutrients, water and electrolytes (44,45). Intraduodenal infusion of different loads of a polymeric enteral diet evoked a normal post prandial small bowel motility response, and colonic inflow volumes even during infusion of high nutrient loads fell within the functional absorptive capacity of the colon. In contrast, intragastric diet infusion was associated with a persistence of fasting small intestinal motility. Despite this, colonic inflow volumes were low and not significantly greater than fasting values. A number of those subjects however, developed diarrhoea during the course of the experiments (44, 45). Clearly, diarrhoea occurring in this experimental setting could not be explained on the basis of disturbed small intestinal physiology, and the findings pointed towards a colonic basis to this important clinical complication of enteral nutrition (46). Further experiments are currently being undertaken to investigate colonic function during enteral feeding. Preliminary results show evidence of water secretion in the ascending colon during intragastric enteral feeding (47). This may tum out to be an important finding and even the clue to the pathogenesis of enteral feeding related diarrhoea. The ascending colon is the major site of fibre degradation (48). It is also the major site of short chain fatty acid(SCFA) absorption (49). SCFAs act as a powerful stimulus to colonic water and electrolyte absorption (50). Could it be therfore that diarrhoea occurs during enteral feeding because the administration of fibre free defined formula diets results in impaired colonic SCFA production which in some instances is so marked as to result in impaired colonic absorption of fluid and electrolytes? If this was the case, there could
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become an important basis to supplementing defined formula diets with a rapidly degradable fibre source to enhance colonic SCFA production. A number of studies have already been carried out to investigate whether fibre supplementation of enteral diets results in a reduced incidence of enteral feeding related diarrhoea (40, 41, 51, 52). All were carried out in patients in intensive care units, and none showed a significant benefit. Intensive care unit patients however are nearly always receiving concomitant antibiotic therapy and indeed in two of the studies (40, 41), there was a correlation between diarrhoea and the administration of antibiotics. Recently we have shown that antibiotics markedly inhibit the bacterial fermentation of fibre (24). It remains possible therefore that enteral feeding related diarrhoea occurs as a consequence of impaired colonic SCFA production and that if this is the case fibre supplementation may have a very beneficial effect as long as the patients are not receiving concomitant antibiotic therapy. If future research confirms this hypothesis then a method other than fibre supplementation of enteral diets will have to be devised to increase colonic luminal SCFAs of patients on antibiotic therapy. Enteral diets and intestinal epithelial cell proliferation Experimental studies The intestinal epithelium can respond to a wide variety of stimuli by altering its proliferative rates (53, 54). There is now a large and interesting literature on the effect of low residue liquid enteral diets on intestinal morphology, cell turnover kinetics and function. Almost all experiments have been performed in the rat, and low residue chemically defined elemental diets and polymeric diets have been studied. In general, in the jejunum, intestinal mass is maintained or increased (55-58) the specific activity of brush border hydrolase activity maintained (55, 56), or increased (57) DNA synthesis rates maintained (55) and absorptive function maintained (58). In shall) contrast, administration of these low residue diets is associated with pronounced atrophy in the ileum (55-58) and colon (55, 59), compared with the feeding of a normal fibre containing rat chow diet. As fibre has been shown experimentally to have a proliferative effect on intestinal epithelium (60, 63). Suggestions have been made that the atrophy and reduced intestinal proliferation seen in rats fed on liquid enteral diets because of the lack of fibre in these diets (58, 59, 64). To prove this hypothesis it would be
necessary to compare the responses of ileal and colonic epithelia to the same liquid enteral diet fed in the absence and presence of added fibre. Results of published studies in general are supportive. Ryan and colleagues showed that cellulose and petroleum jelly added to an oral liquid fibre free diet resulted in significant increases in colonic weight and DNA synthesis rates compared with values seen when the fibre free diet was fed (59). When the same liquid polymeric diet with and without 9% added bulk was administered orally to rats for 4 weeks, however, the total weight of ileal segments were similar (58). In the most comprehensive study to date, Goodlad and colleagues (64) have studied crypt cell production rate in starved rats re-fed a liquid elemental enteral diet supplemented with very large (1:1) quantities of different fibre sources, inert bulk (kaolin), a poorly digestible fibre source (purified wood cellulose), a more readily digestible fibre source(purified wheat bran), and a soluble NSP prepared from ispaghula husk). Crypt cell production rate in the terminal ileum and colon was unaffected by the addition of inert bulk. Of the fibre sources, the most marked crypt cell production rates in terminal ileum and colon were seen when purified wheat bran was added to the diet (64). Unfortunately, no firm conclusions could be reached as to the effect of soluble NSP as not all this diet was consumed. One of the implications of the study of Goodlad et al (64) is that the proliferative effect of added fibre on the distal ileum and colon is related to its digestibility, and thence SCFA formation. It is of interest therefore that other research shows that intraluminal volatile fatty acids (VFAs) stimulate colonic mucosal proliferation (65, 67). Definitive proof that the trophic effects of fibre are due to the products of fibre degradation rather than fibre per se was gained from studies performed in germ free rats, in whom no effect of fibre on colonocyte proliferation was seen (68). Of the three major SCFA liberated during colonic fibre digestion, acetate, propionate and butyrate, butyrate is preferentially metabolised by isolated colonocytes (69). When butyrate (20 mmol/l) was infused for 7 days into the colon of caecectomised rats fed on fibre free elemental diets, colonic mucosal growth, as evidenced by changes in mucosal weight protein and DNA content, was stimulated as effectively as when a mixture of acetate 70 mmol/l, propionate 25 mmol/l, and butyrate 20 mmol/l was infused (70). These experimental animal findings suggest that SCFAs exert a direct trophic effect on colonic epithelium, and that of the three major SCFAs, butyrate exerts the prominent role. These findings have recently been confirmed in man (71); in vitro incubation
110 FIBRE AND ENTERAL NUTRITION
studies showed that to mmol/l butyrate stimulated DNA synthesis to the same extent as a SCFA mixture.
Effect of SCFA in experimental post-operative conditions Rambeau and colleagues have recently moved forward and undertaken a series of animal studies to investigate the effects of fibre and SCFAs on colonic anasto~otic int~grity and an intestinal adaptation follow ing massive small bowel resection (72-74). In the colonic anastomosis model, pectin significantly enhanced colonic mucosal cell proliferation and higher pressures were required to disrupt the anastomosis in animals fed a pectin supplemented diet (72). Colonic infusion of SCFAs was then shown to accelerate wound healing after colonic transection and re-anastomosis (73). Spontaneous anastomotic dehiscence was significantly less in the SCFA than in the control group and, as with pectin, the suture line burst in fewer colons from the SCFA group when tension was applied to the bowel wall (73). In their model of massive (80%) small bowel resection , the addition of pectin to a fibre free chemically defined elemental diet significantly enhanced small intestinal and colonic adaptation (74). Interestingly, ~nder the same experimental conditions, parenterally mfusedSCFA led to a significant enhancement of the adaptive response only in the jejunum and ileum and not in the colon (75). The most recent animal studies reported by this group indicate that the trophic effects of SCFAs on the colon are luminally and not parenterally mediated (76). The evidence summarised above suggests that there could be advantages in incorporating a rapidly degradable fibre source in defined formula enteral diets. The proliferative effects of fibre are however related to the production of the end products of fermentation, namely SCFAs. Clinicians should be wary therefore of assuming that advantages of fibre supplemented diets will accrue in patients receiving antibiotic therapy.
Fibre and gut barrier function There is much evidence in the old literature that starvation results in atrophy of the villous architecture. Similar findings have been described during long term parenteral nutrition in animals (77) and in the segments o~ human small intestine surgically bypassed for obesity (78). The lack of luminal nutrit ion plays a
pivotable role in producing these change, presumably by inhibiting the production of hormones acting on the gut. Although the knowledge that depriv ing the gut of luminal nutrition has a deleterious effect on intestinal morphology has provided a powerful argument for providing nutritional support where ever possible via the enteral rather than the parenteral route the story does not end here. Changes in intestinal morphology have been shown to be associated with changes in barrier function. Thus, not only does parenteral nutrition adversely affect the morphology of experimental animals but it is also associated with the pas sage of viable bacteria from the gastro-intestinal tract to otherwise sterile tissue such as mesentery lymph nodes (MLN) liver and spleen (79), a phenomenon that is known as bacterial translocation. Experimental studies show that bacterial translocation occurs to a significantly lesser extent in animals receiving enteral rather than parenteral feeding (77). Bacterial translocation has now been shown to occurr in experimental animals submitted to a number of stimuli including bums, trauma, sepsis, mesenteric ischaemia and intestinal bacterial overgrowth (80). Bacterial translocation can be potentiated by prote in m~lnutri.ti?n (81) and specifically by essential fatty acid deficiency (82). There is now experimental evidence to show that partial loss of intestinal barrier function may be reversed by luminal nutrition either in the form of oral nutrition (83) or as suggested in some experiments by glutamine alone (84). Although the clinical significance of bacterial translocation is unclear, translocating bacteria have been hypothesised as a potential source of sepsis in critically ill patients. If this hypothesis is correct then the protective effects of luminal nutrition so far demonstrated may tum out to be of unparalled importance because it will elevate the status of enteral nutrition at least in critically ill patients, from supportive to primary therapy. Clearly one important question that arises when considering concepts of fibre and enteral nutrition is wh~ther there is any evidence that fibre or its degradation p~oducts ~ave any specific effects in madifying gut barr ier funct ion. Experiments today prov ide interesting but conflicting data. The addition of cellulose to an orally administered total parenteral nutrition solution reduces the incidence of bacterial translocation in experimental animals (85). In a similar experimental model citrus pectin exhibited no such effect (86). 1.'he addition of corn cobs but not soy fibre to a defined fibre free formula diet in a further study reduced the ~anslocation. rate significantly (87). Neither glutamme nor psyllium fibre when added to a fibre free
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formula diet protected effectively against spontaneous or endotoxin induced bacterial translocation (88). Clearly, therefore, much further work is needed in this area, but there is much preliminary evidence to suggest that the addition of fibre to fibre free defined formula diet may exert a beneficial effect an gut barrier function.
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rat colonic structure and mucosal cell growth. J Nutr 1981; 111:789-803 Tasman Jones C, Owen R L, Jones A L. Semipurified dietary fibre and small bowel morphometry in rats. Dig Dis Sci 1982; 27:519-524 Jacobs L R, Lupton J R. Effects of dietary fibres on rat large bowel mucosal growth and cell proliferation. AM J Physiol 1984;6:378-385 Goodlad R A, Lenton W, Ghatei M A, Adrian T E, Bloom S R, Wright N A. Effects of an elemental diet, inert bulk and different types of dietary fibre on the response of the intestinal epithelium to refeeding in the rat and relationship to plasma gastrin, enteroglucagen and PYY concentrations. Gut 1987; 28; 171-180 Sakata T, Enghardt W V. Stimulating effect of shari chain fatty acids on the epithelial cell proliferation in the rat large intestine (Abstract). Comp Biochem Physiol 1983; 74A:49-462 Sakata T. Short chain fatty acids as the luminal trophic factor. Can J Amin Sci 1984; 64: 189-190 Sakata T, Yajima T. Influence of short chain fatty acids on the epithelial cell division of digestive tract. Am J Exp Physiol 1984;69:639~48
68. Goodlad R A, Ratcliffe B, Fordham J P, Wright N A. Does dietary fibre stimulate intestinal epithelial cell proliferation in germ free rats? Gut 1989: 30: 82Q-825 69. Roediger W E W. Utilization of nutrients by isolated epithelial cells of the rat colon. Gastroenterology 1982; 83: 424-429 70. Kripke S A, Fox A D, Berman J M, De Paula J, Sellte R G, Rornveau J L, Short chain fatty acids and colonic mucosal growth: importance of butyrate. Clin Nutr 1987; 6(Suppl): 38 71. Scheppach W, Bartram P, Richter A et al. The effect of shortchain fatty acids on the human colonic mucosa in vitro. JPEN 1992; 16;43-48 72. Rolandelli R H, Koruda M J, Sellte R G, Rombeau J 1. The effect of enteral feedings supplemented with pectin in the healing of colonic anastomosis in [he rat. Surgery 1986; 99:703-707 73. Rolandelli R H, Koruda M J, Settle R G, Rombeau, J 1. Effects of intraluminal infusion of short-chain fatty acids on the healing of colonic anastomosis in the rat. Surgery 1986; 100: 198-203 74. Koruda M J, Rolandelli R H, Settle R G, Saul S H, Rombeau J 1. The effect of a pectin supplemented elemental diet on intestinal adaptation to massive small bowel resection. JPEN 1986; 10: 343-350 75. Koruda M J. Rolandelli R H, Settle R G, Zimmaro D M, Rombeau J L. Effect of parenteral nutrition supplemented with short-chain fatty acids on adaptation to massive small bowel resection. Gastronenterology 1988; 95: 715-720 76. Frankel W, Singh A, Zhang W, Bain A, Klurfeld D, Rornbeau J. Colonostrophic effects of short-chain fatty acids are mediated locally. Clin Nutr 1992; 11(Suppl): 63 77. Johnson L R, Copeland E M, Dudrick S J et al. Structural and hormonal alterations in the gastrointestinal tract of parenterally fed rats. Gastroenterology 1975; 68: 1177-1183 78. Daly J M. Castro G A, Akhtar M, Dudrick S J. Morphologic and biochemical intestinal changes after jejune-ileal by-pass, (Abstract). Gastroenterology 1977; 72: 1042 79. Alverdy J C, Aoys E, Moss G S. Total parenteral nutrition promotes bacterial translocation from the gut. Surgery 1988; 104: 185-190 80. Wells C L, Maddaus M A, Simmons R 1. Proposed mechanism for the translocation of intestinal bacteria. Rev Infec Dis 1988; 10: 958-979 81. Deitch E A, Winterton 1, Li M et al. The gut as a portal of
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entry for bacteremia: Role of protein malnutrition. Ann Surg 1987;205:681-692 Barton R G, Cerra F B, WelIs C L. Effect of a diet deficientin essential fatty acids on the translocation of intestinalbacteria. JPEN 1992; 16,2: 122-128 Wells C L, Jechorek R P, Evlandsen S G et aJ.The effect dietary glutamine and dietary RNA a ileal flora, ileal histology, and bacterial translocationin nuce. Nutrition 1990; 6:70-75 Souba W W. Klimberg V S. Hantakeaki R D. et al, Oval glutamine reduces bacterial translocation following abdominal radiation J. Sorgo Res 1990; 48: 1-5 Shennan P, Soni R, Karmali, Attaching and effacing adherence of vero cytotoxin-producing escherichiacoli to
rabbit intestinalepithelium in vivo. Infect Imrnun 1988; 56:756--761 86. Spaeth G. Specian R D. Berg R D, Deitch E A. Bulk
preventsbacteria!translocation inducedby the oral administration of tota! parenteral nutritionsolutin. JPEN 1990; 14:442--447 87. AlverdyJ C, AoysE, MossG S. Effect of commercialIy availablechemicalIy definedliquiddiets on the intestinal microfloraand bacterialtranslocation from the gut. JPEN 1990; 14: 1-6 88. BarberA E, Jones W G, MineiJ P et aJ. Glutamine or fibre supplementation of a definedformuladiet: Impacton bacterial translocation, tissuecomposition and responseto endotoxin. JPEN 1990; 14: 335-343
Fibre and enteral nutrition D.S.A. SILK Department of Gastroenterology and Nutrition, Central Middlesex Hospital NHS Trust, Acton Lane, London NW10 7NS, UK
Introduction Clinical experience during the last decade has confinned that enteral nutrition is an efficient and cost effective means of providing nutritional support to patients with normal or near normal gastro-intestinal function (1). Before and during this period the knowledge gained of the processes involved in the physiology of nutrient absorption has been applied to the formulation of enteral diets; and if comparisons are made of the composition of present day diets with those used 10-15 years ago several differences can be seen. These relate mainly to the nitrogen and energy concentrations of polymeric diets, and the sources of nitrogen and energy and electrolyte compositions of predigested chemically defined elemental diets (2). Until recently all the commercially produced liquid enteral diets continued to have one thing in common, namely that they contained a low residue or low 'fibre' content. The very earliest low residue enteral diets were specifically designed not only to provide balanced nutrition to astronauts in space, but also to reduce their stool weight and stool frequency (3). Subsequently it was realised that one clinical advantage of low residue diets was that they had a low viscosity and could be administered easily through 'fine bore' nasogastric or nasoenteric feeding tubes. Furthermore as it became clear that there could even be a number of therapeutic advantages in administering low residue diets (4) their widespread use became accepted without question. Although the 1970s and early 1980s has been the time when advances have been achieved in the field of enteral nutrition the same period has seen also significant advances in the field of fibre research and as a consequence there has developed a belief that many of the diseases of western civilisation such as atherosclerosis, obesity, appendicitis, constipation, irritable bowel syndrome, colon cancer, diverticular disease, diabetes mellitus and gallstones were related to a deficiency in dietary fibre, and that supplementing the diet with fibre would prevent and might even cure these conditions (5). Although not all recent studies (6) have been in complete agreement the observations 106
made by Heaton and colleagues over 10 years ago (7, 8) that ingestion of bran accelerated slow intestinal transit and delayed rapid intestinal transit, lead to suggestions that the ingestion of fibre produces a more regular bowel habit (9). Based largely on the above premise as well as on the fashionable doctrine that dietary fibre was good overall, suggestions began to be made in the second half of the 1980s that there could be benefits to supplementing commercially produced liquid enteral diets with fibre. In 1989, our Unit published the first major review on fibre and enteral nutrition (10). Attempts were made to critically examine the premises on which the proposed use of fibre supplemented enteral diets were based. The definition of dietary fibre was discussed (11), the physiology of dietary fibre assimilation reviewed and particular attention was paid to discussing the factors affecting the breakdown of non starch polysaccharide (NSP) in man. Of importance in relationship to the clinical applications of fibre supplementation in enteral feeding was the fact that non-cellulosic polysaccharide (NCP) components of dietary fibre are known to be degraded more efficiently than cellulose (11). The influence of important physical properties such as solubility (12), particle size (13) and surface area (14, 15) on the degree of digestibility was emphasised as was the influence that the substrate inducibility of the colonic bacterial polysaccharidase enzyme systems would likely to exert on fibre degradation (16). As a consequence of these discussions it was suggested that the physical characteristics of the fibre sources being used clinically in enteral feeding were likely to rapidly degrade, not only because most were predominantly NCP, but because particle size was small (in order to overcome viscosity problems), and since only single fibre sources were being employed, digestibility would increase with time, a situation which was envisaged during long term administration of fibre supplemented enteral diets (10). Two main areas of interest in fibre and enteral nutrition were identified, namely effect on bowel function and effects on small and large intestinal mucosal
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cell morphology (16). A particular area of interest that developed later, concerned with the effects of fibre supplementation on mucosal barrier function has arisen. This article seeks to update progress that has been made in these areas. Fibre and enteral nutrition - effect on bowel function
Constipation Studies of healthy volunteers have shown that the majority of the population in the Western World pass one bowel movement per day with an average daily output 120-130 g stool (17). Similar findings were reported in normal subjects taking part in dietary studies and consuming metabolically controlled diets (18). Large individual variation is seen, however, both in frequency and weight of bowel movements, without complaints of either constipation or diarrhoea (19). Such variability in normal bowel habit makes it difficult to define an abnormal or constipated state and to date this basic difficulty has not been overcome (19). Clinical studies in which fibre free defined formula enteral diets have been administered to normal healthy volunteers suggest that wet stool weights in the range of 40-70 g/d in the norm with a daily stool frequency of 0.5-0.7 (20-23). Based on the known effects that increasing the intake of dietary fibre has on bowel function (10) most investigations have sought to show that supplementing fibre free enteral diets with fibre results in increases in daily stool wet weights and transit time. Certainly these have been the main goals of investigators who have carried out studies in normal healthy subjects as well as in stable medical patients and those with psychiatric or neurological disorders. Although Slavin and colleagues (20) showed that the addition of 30 and 60 gld soy fibre to a fibre free defined formula diet administered to normal healthy volunteers resulted in significant increases in daily wet stool weight (60 g/d) and daily stool frequency the findings of other studies carried out in normal healthy volunteers have been less impressive (21). Direct comparisons of data are unwarranted however, as experimental designs have not been standardised. In our Unit, we have been interested in investigating the differential effects of readily metabolised and relatively poorly metabolised fibre sources on bowel function of normal human volunteers fed fibre free and fibre supplemented diets (24, 25). Positive effects have been minimal even where a poorly metabolised oat fibre source was studied (26).
One interesting recent study (27) has shown that the administration of a fibre free chemically defined elemental diet to normal human volunteers resulted in the passage of liquid stools in 60% of subjects. The addition of pectin (range 14.5-31.5 gld) abolished the liquid stools (27). Two controlled studies have been performed in stable medical patients (23, 28). Neither the addition of 24 gld carrot fibre nor 12.4 gld and 38.5 g/d of soy polysaccharide fibre to fibre free liquid formulae resulted in any significant change in the parameters of bowel function studied. In a prospective crossover study performed in 28 mentally retarded young individuals suffering from chronic constipation as a consequence of fibre free enteral feeding, the addition of soy polysaccharide (15.6-17.4 g/d) for 2 weeks was without effect on stool weight, stool frequency or transit time (22). In a subsequent study from the same Unit (29) a 1 year trial in 11 mentally retarded patients showed that supplementation of a fibre free liquid diet administered via gastrostomy with 18-25 gld soy fibre resulted in a significant increase in stool weights (30 ± SD 13 g/d vs 87 ± g/d) and bowel frequency 0.6 ± 0.2 vs 1.1 ± 0.5). One final study carried out in patients with neurological disorders (30) is difficult to interpret as the mean wet stool weights in the patients receiving long term tube feeding with a fibre free diet were much higher (142.6 g/d) than one would have expected. The requirements of laxatives were reported to be significantly less when the patients received the same diet supplemented with 12.8 gIL soy fibre. One is forced to conclude as a consequence of the above studies that the supplementation of fibre free defined formula diets with a single fibre source results in only marginal benefits in respect of bowel function and that the positive benefits shown are of questionable clinical significance. Rapidly degraded fibre sources increase faecal weight by virtue of the fact that they stimulate growth of microflora within the colon (31, 32). Poorly digested fibre on the other hand, stimulates bacterial growth to a lesser degree, but survives to hold water (33). Poorly degraded fibre produces larger faecal weights than equivalent supplements of more rapidly degraded fibre (19, 31). It is perhaps hardly surprising therefore that the studies described above, most of which have employed the use of well degradable small particle sized single sources of predominantly non cellulosic polysaccharide containing fibre, have produced such modest improvements in bowel function. If in the future, there remains a demand to improve bowel function in patients receiving long term enteral feeding then a different strategy will be required.
lOH
FIBRE AND ENTERAL NUTRITION
Possibilities would seem to include the use of multiple fibre sources that in tum should be varied to overcome the problem of substrate inducibility of the colonic bacterial polysaccharidase enzyme systems (16). Consideration might be given to the use of more poorly degraded fibre sources. Caution is required though as the oat fibre studied by our group (26) was without effect on bowel function, and the use of cellulose as a fibre supplement resulted in the production of hard pellety stools that were painfully difficult to pass (34). Much innovative thinking and research will be required before the problems of sluggish bowel function and low stool weights in patients on long term enteral feeding are overcome.
Diarrhoea Diarrhoea is a significant problem in enteral nutrition. According to basic physiological principles, which take into account the capacity of the normal small and large intestine to assimilate fluid and electrolytes, diarrhoea can be defined as the passage of more than 200 g of stool/24 h on an average Western diet (35). It follows that the diagnosis of diarrhoea is dependent on accurate measurements of stool outputs, hardly a feasible proposition in uncooperative enterally fed patients with faecal incontinence. For the purposes of our clinical studies we have therefore defined enteral feeding related diarrhoea as the passage of too frequent stools or stools of too loose a consistency that are of inconvenience to the nursing staff and/or the patient (36, 37). In our original experience, diarrhoea so defined, occurred in up to 25% of patients receiving enteral nutrition (38). A number of factors have been implicated in its pathogenesis (1). These include use of infected feeds, lactose intolerance, intolerance of high osmotic loads of nutrients administered, inappropriate release of gastro-intestinal polypeptide hormones, concomitant antibiotic therapy, ingestion of laxatives, and hypoalbuminaemia. The role of lactose intolerance in the pathogenesis of the diarrhoea has been discussed in some detail (1). In brief, the deleterious effect of lactose in enterally fed patients with lactose intolerance will depend on the load (concentration x rate) of lactose administered. Bolus feeding in lactose intolerant patients results in the production of stool volumes in excess of 1 1/24 h (39). In contrast, when a low load of lactose is presented to the upper small intestine, as occurs during constant 24-h intragastric infusion of liquid lactose containing diets, diarrhoea does not occur (36). In a prospective controlled trial of continuous 24-h nasogastric infusion of polymeric diets to patients with normal or near normal gastro-intestinal
function, the development of diarrhoea was not related to osmotic load of nutrients presented for absorption but to concomitant antibiotic therapy (37) an abservation that has subsequently been confirmed (40,41). Animal studies carried out in our laboratory have not confirmed that the onset of diarrhoea is related to an inappropriate release of gastro-intestinal polypeptide hormones (42). Finally, hypoalbuminaemia has been related to the development of diarrhoea (43). Disappointed that so little progress was being made in achieving a greater understanding of the pathogenesis of enteral feeding related diarrhoea, we have undertaken a series of intubation studies in normal human subjects receiving continuous intragastric or intraduodenal enteral feeding. For the first series of experiments we devised and validated a multilumen orocaecal intubation technique that has permitted the study of small intestinal motility responses to the enteral feeding as well as permitting quantitative of colonic inflows of nutrients, water and electrolytes (44,45). Intraduodenal infusion of different loads of a polymeric enteral diet evoked a normal post prandial small bowel motility response, and colonic inflow volumes even during infusion of high nutrient loads fell within the functional absorptive capacity of the colon. In contrast, intragastric diet infusion was associated with a persistence of fasting small intestinal motility. Despite this, colonic inflow volumes were low and not significantly greater than fasting values. A number of those subjects however, developed diarrhoea during the course of the experiments (44, 45). Clearly, diarrhoea occurring in this experimental setting could not be explained on the basis of disturbed small intestinal physiology, and the findings pointed towards a colonic basis to this important clinical complication of enteral nutrition (46). Further experiments are currently being undertaken to investigate colonic function during enteral feeding. Preliminary results show evidence of water secretion in the ascending colon during intragastric enteral feeding (47). This may tum out to be an important finding and even the clue to the pathogenesis of enteral feeding related diarrhoea. The ascending colon is the major site of fibre degradation (48). It is also the major site of short chain fatty acid(SCFA) absorption (49). SCFAs act as a powerful stimulus to colonic water and electrolyte absorption (50). Could it be therfore that diarrhoea occurs during enteral feeding because the administration of fibre free defined formula diets results in impaired colonic SCFA production which in some instances is so marked as to result in impaired colonic absorption of fluid and electrolytes? If this was the case, there could
CLINICAL NUTRITION 109
become an important basis to supplementing defined formula diets with a rapidly degradable fibre source to enhance colonic SCFA production. A number of studies have already been carried out to investigate whether fibre supplementation of enteral diets results in a reduced incidence of enteral feeding related diarrhoea (40, 41, 51, 52). All were carried out in patients in intensive care units, and none showed a significant benefit. Intensive care unit patients however are nearly always receiving concomitant antibiotic therapy and indeed in two of the studies (40, 41), there was a correlation between diarrhoea and the administration of antibiotics. Recently we have shown that antibiotics markedly inhibit the bacterial fermentation of fibre (24). It remains possible therefore that enteral feeding related diarrhoea occurs as a consequence of impaired colonic SCFA production and that if this is the case fibre supplementation may have a very beneficial effect as long as the patients are not receiving concomitant antibiotic therapy. If future research confirms this hypothesis then a method other than fibre supplementation of enteral diets will have to be devised to increase colonic luminal SCFAs of patients on antibiotic therapy. Enteral diets and intestinal epithelial cell proliferation Experimental studies The intestinal epithelium can respond to a wide variety of stimuli by altering its proliferative rates (53, 54). There is now a large and interesting literature on the effect of low residue liquid enteral diets on intestinal morphology, cell turnover kinetics and function. Almost all experiments have been performed in the rat, and low residue chemically defined elemental diets and polymeric diets have been studied. In general, in the jejunum, intestinal mass is maintained or increased (55-58) the specific activity of brush border hydrolase activity maintained (55, 56), or increased (57) DNA synthesis rates maintained (55) and absorptive function maintained (58). In shall) contrast, administration of these low residue diets is associated with pronounced atrophy in the ileum (55-58) and colon (55, 59), compared with the feeding of a normal fibre containing rat chow diet. As fibre has been shown experimentally to have a proliferative effect on intestinal epithelium (60, 63). Suggestions have been made that the atrophy and reduced intestinal proliferation seen in rats fed on liquid enteral diets because of the lack of fibre in these diets (58, 59, 64). To prove this hypothesis it would be
necessary to compare the responses of ileal and colonic epithelia to the same liquid enteral diet fed in the absence and presence of added fibre. Results of published studies in general are supportive. Ryan and colleagues showed that cellulose and petroleum jelly added to an oral liquid fibre free diet resulted in significant increases in colonic weight and DNA synthesis rates compared with values seen when the fibre free diet was fed (59). When the same liquid polymeric diet with and without 9% added bulk was administered orally to rats for 4 weeks, however, the total weight of ileal segments were similar (58). In the most comprehensive study to date, Goodlad and colleagues (64) have studied crypt cell production rate in starved rats re-fed a liquid elemental enteral diet supplemented with very large (1:1) quantities of different fibre sources, inert bulk (kaolin), a poorly digestible fibre source (purified wood cellulose), a more readily digestible fibre source(purified wheat bran), and a soluble NSP prepared from ispaghula husk). Crypt cell production rate in the terminal ileum and colon was unaffected by the addition of inert bulk. Of the fibre sources, the most marked crypt cell production rates in terminal ileum and colon were seen when purified wheat bran was added to the diet (64). Unfortunately, no firm conclusions could be reached as to the effect of soluble NSP as not all this diet was consumed. One of the implications of the study of Goodlad et al (64) is that the proliferative effect of added fibre on the distal ileum and colon is related to its digestibility, and thence SCFA formation. It is of interest therefore that other research shows that intraluminal volatile fatty acids (VFAs) stimulate colonic mucosal proliferation (65, 67). Definitive proof that the trophic effects of fibre are due to the products of fibre degradation rather than fibre per se was gained from studies performed in germ free rats, in whom no effect of fibre on colonocyte proliferation was seen (68). Of the three major SCFA liberated during colonic fibre digestion, acetate, propionate and butyrate, butyrate is preferentially metabolised by isolated colonocytes (69). When butyrate (20 mmol/l) was infused for 7 days into the colon of caecectomised rats fed on fibre free elemental diets, colonic mucosal growth, as evidenced by changes in mucosal weight protein and DNA content, was stimulated as effectively as when a mixture of acetate 70 mmol/l, propionate 25 mmol/l, and butyrate 20 mmol/l was infused (70). These experimental animal findings suggest that SCFAs exert a direct trophic effect on colonic epithelium, and that of the three major SCFAs, butyrate exerts the prominent role. These findings have recently been confirmed in man (71); in vitro incubation
110 FIBRE AND ENTERAL NUTRITION
studies showed that to mmol/l butyrate stimulated DNA synthesis to the same extent as a SCFA mixture.
Effect of SCFA in experimental post-operative conditions Rambeau and colleagues have recently moved forward and undertaken a series of animal studies to investigate the effects of fibre and SCFAs on colonic anasto~otic int~grity and an intestinal adaptation follow ing massive small bowel resection (72-74). In the colonic anastomosis model, pectin significantly enhanced colonic mucosal cell proliferation and higher pressures were required to disrupt the anastomosis in animals fed a pectin supplemented diet (72). Colonic infusion of SCFAs was then shown to accelerate wound healing after colonic transection and re-anastomosis (73). Spontaneous anastomotic dehiscence was significantly less in the SCFA than in the control group and, as with pectin, the suture line burst in fewer colons from the SCFA group when tension was applied to the bowel wall (73). In their model of massive (80%) small bowel resection , the addition of pectin to a fibre free chemically defined elemental diet significantly enhanced small intestinal and colonic adaptation (74). Interestingly, ~nder the same experimental conditions, parenterally mfusedSCFA led to a significant enhancement of the adaptive response only in the jejunum and ileum and not in the colon (75). The most recent animal studies reported by this group indicate that the trophic effects of SCFAs on the colon are luminally and not parenterally mediated (76). The evidence summarised above suggests that there could be advantages in incorporating a rapidly degradable fibre source in defined formula enteral diets. The proliferative effects of fibre are however related to the production of the end products of fermentation, namely SCFAs. Clinicians should be wary therefore of assuming that advantages of fibre supplemented diets will accrue in patients receiving antibiotic therapy.
Fibre and gut barrier function There is much evidence in the old literature that starvation results in atrophy of the villous architecture. Similar findings have been described during long term parenteral nutrition in animals (77) and in the segments o~ human small intestine surgically bypassed for obesity (78). The lack of luminal nutrit ion plays a
pivotable role in producing these change, presumably by inhibiting the production of hormones acting on the gut. Although the knowledge that depriv ing the gut of luminal nutrition has a deleterious effect on intestinal morphology has provided a powerful argument for providing nutritional support where ever possible via the enteral rather than the parenteral route the story does not end here. Changes in intestinal morphology have been shown to be associated with changes in barrier function. Thus, not only does parenteral nutrition adversely affect the morphology of experimental animals but it is also associated with the pas sage of viable bacteria from the gastro-intestinal tract to otherwise sterile tissue such as mesentery lymph nodes (MLN) liver and spleen (79), a phenomenon that is known as bacterial translocation. Experimental studies show that bacterial translocation occurs to a significantly lesser extent in animals receiving enteral rather than parenteral feeding (77). Bacterial translocation has now been shown to occurr in experimental animals submitted to a number of stimuli including bums, trauma, sepsis, mesenteric ischaemia and intestinal bacterial overgrowth (80). Bacterial translocation can be potentiated by prote in m~lnutri.ti?n (81) and specifically by essential fatty acid deficiency (82). There is now experimental evidence to show that partial loss of intestinal barrier function may be reversed by luminal nutrition either in the form of oral nutrition (83) or as suggested in some experiments by glutamine alone (84). Although the clinical significance of bacterial translocation is unclear, translocating bacteria have been hypothesised as a potential source of sepsis in critically ill patients. If this hypothesis is correct then the protective effects of luminal nutrition so far demonstrated may tum out to be of unparalled importance because it will elevate the status of enteral nutrition at least in critically ill patients, from supportive to primary therapy. Clearly one important question that arises when considering concepts of fibre and enteral nutrition is wh~ther there is any evidence that fibre or its degradation p~oducts ~ave any specific effects in madifying gut barr ier funct ion. Experiments today prov ide interesting but conflicting data. The addition of cellulose to an orally administered total parenteral nutrition solution reduces the incidence of bacterial translocation in experimental animals (85). In a similar experimental model citrus pectin exhibited no such effect (86). 1.'he addition of corn cobs but not soy fibre to a defined fibre free formula diet in a further study reduced the ~anslocation. rate significantly (87). Neither glutamme nor psyllium fibre when added to a fibre free
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formula diet protected effectively against spontaneous or endotoxin induced bacterial translocation (88). Clearly, therefore, much further work is needed in this area, but there is much preliminary evidence to suggest that the addition of fibre to fibre free defined formula diet may exert a beneficial effect an gut barrier function.
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