Bacterial translocation during enteral and parenteral nutrition

Microbial translocation can be defined as the passage of both viable and non-viable microbes and microbial products across the intact intestinal barrier. In human subjects, translocation may be important in the hypermetabolic response to injury, a septic state in the absence of a defined focus, the development of distant infections, and multiple organ failure. The load of microbial products, such as endotoxin, and their role in inciting inflammatory and cytokine responses may be as important or more important than the presence of the organisms themselves. Translocation is not a new phenomenon; it was vaguely suggested by the writings of Fraenkel(l891). Several more papers in the early 1900s suggested that organisms could penetrate through the intact bowel wall (Alexander & Gennari, 1996), but it was really the work of Arnold and his colleagues in 1928-30 (Arnold, 1928, 1930; Arnold & Brody, 1928) that provided a clear indication for the role of translocation in producing systemic illness in animals. Of interest, he was able to show that alkalinization of the intestinal contents significantly increased the incidence of translocation, and that translocation occurred very early, as soon as 5 min after introduction of bacteria into the lumen of the intestine. Flory (1933) was able to show that translocation occurred through a trans-epithelial process, i.e. through the enterocytes, rather than between them. In the 1950s, Jacob Fine and his colleagues (Fine et al. 1952) established compelling relationships between translocation and irreversible haemorrhagic shock. Numerous diseases have been found to be associated with translocation in man (Alexander & Gennari, 1996). These include pneumatosis intestinalis, non-occlusive intestinal gangrene, necrotizing enterocolitis, radiation injury, response to cytotoxic drugs, the cytokine release syndrome, Crohn’s disease, ulcerative colitis, haemorrhagic shock, severe trauma, cerebral injury, leukaemia, neutropenia, and colon cancer. Translocation from the intestine is most commonly detected by measuring the presence of viable bacteria in the tissues. This can reflect not only the integrity of the intrinsic barrier function of the mucosa but also the numbers and types of microbes in the lumen and the ability of the host to kill the bacteria that do translocate. Translocation may occur by three mechanisms: through M cells, which is a normal processing pathway; through epithelial cells, which increases after systemic injury; through ulcerations, which is an important pathway after cellular injury, such as caused by cytotoxic drugs or radiation (Alexander & Gennari, 1996). Translocation through the tight junctions has not been observed. Factors that increase microbial translocation, as measured by bacterial counts in the tissues, include: diminished blood flow or 0 2 delivery, e.g. haemorrhagic shock, bum injury, administration of zymosan or endotoxin, mesenteric occlusion, hypoxia or fever; immunosuppression, e.g. high-dose prednisone or blood transfusions; changes in the intestinal microbial density, e.g. following antibiotic therapy or the administration of an elemental diet or total parenteral nutrition (TPN); direct damage to the epithelium, e.g. irradiation, cytotoxic drugs, irritants, cytomegalovirus infection, mucosal disease, bowel manipulation, bowel obstruction or reperfusion injury (Alexander & Gennari, 1996). Drugs which will decrease bacterial translocation can be divided into several broad categories: those which will improve the microcirculation of the intestine, e.g. enalopril or prostaglandin El or E2 analogues; those which increase mucus production, e.g. prostaglandins El or E2 analogues, sucralfate; those which act as growth factors (basic fibrobast growth factor, granulocyte macrophage colony-stimulating factor, epidermal growth factor, bombesin or insulin-like growth factor-1); those which decrease inflammatory damage, e.g. allopurinol, or anti-interleukin 6. Antibiotics themselves do not seem to influence the mucosal barrier, except via alteration of the numbers and types of microbes in the intestinal lumen (Alexander & Gennari, 1996).