Hypersensitivity angiitis in a dormant black bear (Ursus americanus).
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Biomedical subjects
Publications and source records attributed to C L Wells.
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Members of the endogenous flora have become recognized as major pathogens in nosocomial infections, and the intestinal tract has become recognized as a major portal of entry for these pathogens. The English-language literature on this topic has been summarized and a working hypothesis devised describing a mechanism whereby intestinal bacteria can escape and cause systemic disease. It is postulated that the motile phagocyte ingests intestinal bacteria, transports them to extraintestinal sites, fails to accomplish intracellular killing, and then liberates the bacteria in the extraintestinal site. This hypothesis is consistent with many observations found in the literature: (1) The intestinal bacteria that most readily translocate out of the intestinal tract are classified as facultative intracellular pathogens. (2) Intestinal particles with no intrinsic motility (e.g., yeast, ferritin, starch) can translocate out of the intestinal lumen within hours after their ingestion. (3) The rate of translocation of intestinal bacteria can be altered with agents that modulate immune (including phagocytic) function. In the context of the mechanisms involved in intestinal immune responses, bacterial translocation appears to be a part of the normal antigen-sampling process of gut-associated lymphoid tissue. Systemic disease caused by translocating intestinal bacteria could be due to a maladaptation of the antigen-sampling process that has been designed to regulate the immune response to intestinal antigens.
BACKGROUND: There are several reports indicating that the isoflavone genistein may augment the integrity of the intestinal epithelial barrier as well inhibit bacterial internalization by cultured enterocytes. We speculated that oral genistein might enhance the integrity of the intestinal epithelial barrier as monitored by the extraintestinal dissemination of intestinal bacteria. METHODS: Mice were treated with oral antibiotics to induce cecal bacterial overgrowth accompanied by bacterial translocation of antibiotic-resistant enterobacteria, especially Escherichia coli. These mice were divided into separate groups that included chow-fed mice orally inoculated either with saline, vehicle, or genistein, and mice fed isoflavone-free diet and orally inoculated with either saline, vehicle, or genistein. Intestinal bacterial overgrowth was monitored by quantitative culture of excised ceca and bacterial translocation was monitored by quantitative culture of draining mesenteric lymph nodes. RESULTS: Mice fed the isoflavone-free diet had decreased populations of cecal bacteria compared with chow-fed mice, and bacterial translocation was reduced in chow-fed mice compared with mice fed isoflavone-free diet. However, bacterial translocation was similar in mice given oral genistein compared with appropriate control mice. CONCLUSIONS: Oral genistein had no noticeable effect on bacterial translocation in this model. However, the isoflavone-free diet had an antibacterial effect on cecal flora, and the isoflavone-free diet was associated with decreased numbers of cecal bacteria and decreased incidence of bacterial translocation.
Normal intestinal bacteria can initiate systemic disease by translocating out of the intestinal lumen to extraintestinal sites such as the mesenteric lymph nodes (MLN), liver, and spleen. To determine whether dietary essential fatty acids can affect the incidence of bacterial translocation, separate groups of mice were fed one of two diets for 8 days: an essential fatty acid-replete diet (EFA-R) containing a basal formula supplemented with arginine, yeast RNA, menhaden oil, and safflower oil, or an essential fatty acid-deficient diet (EFA-D) containing the same ingredients with the safflower oil replaced by menhaden oil. Mice were given either diet alone, diet plus 50 micrograms of intraperitoneal lipopolysaccharide (LPS), or diet plus 3 days of 4 mg of intramuscular metronidazole (MET) three times a day. (Both LPS and MET have been shown to increase the incidence of bacterial translocation to the MLN.) Within treatment groups there were no significant differences in the total numbers of viable ileal bacteria (separate quantitation of strict anaerobes, aerobic, and facultative Gram-positive results, and aerobic and facultative Gram-negative results). The incidence of bacterial translocation to the MLN was increased in mice fed EFA-D as compared with EFA-R in mice treated with diet alone (17% vs 0%; p less than .005) and in mice treated with diet plus LPS (71% vs 48%; p = .027). There was no difference in the incidence of bacterial translocation in mice fed EFA-D or EFA-R and treated with MET (83% vs 81%).
Liquid Isosource was supplemented with soy fiber (Isosource-soy) or guar fiber (Isosource-guar) to study the effects of fiber supplementation of a liquid diet on the composition of mouse cecal flora and on the incidence of bacterial translocation, quantified as the number of mice with viable intestinal bacteria recovered from mesenteric lymph nodes. Mice fed chow, Isosource, Isosource-soy, or Isosource-guar had similar concentrations of cecal bacteria and similarly low incidences of bacterial translocation. In separate experiments, mice were given parenteral metronidazole or parenteral lipopolysaccharide (LPS) to induce cecal bacterial overgrowth and bacterial translocation. Compared with mice treated with diet alone, metronidazole- or LPS-treated mice had high numbers of cecal bacteria and high incidences of bacterial translocation. However, among the dietary groups of LPS-treated mice, the incidence of translocation was significantly less in mice fed Isosource-soy or Isosource-guar compared with mice fed unsupplemented Isosource. These results suggest that soy or guar supplementation of Isosource might be beneficial in some circumstances.
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Separate groups of mice were fed either standard rodent chow or one of three liquid diets (Impact, Isosource HN, Fibersource HN) for 14 days to determine the effects of these liquid diets on the cecal bacterial flora and on the incidence of bacterial translocation to the mesenteric lymph nodes. Liquid Isosource and liquid Fibersource had no noticeable effect on either the cecal bacterial flora or the incidence of bacterial translocation. Liquid Impact was associated with cecal bacterial overgrowth but had no effect on the incidence of bacterial translocation. Each of the liquid diets was then lyophilized and similarly fed to mice; none of the lyophilized diets had a noticeable effect on the cecal bacterial flora or the incidence of bacterial translocation. To test these liquid and lyophilized diets in stressed mice, separate groups of mice were again fed the various diets for 14 days but given parenteral Escherichia coli lipopolysaccharide (LPS) 24 h before being killed. None of the liquid or lyophilized diets had a noticeable effect on the cecal bacterial overgrowth noticed in LPS-treated chow-fed mice. Compared with chow-fed mice, the typically elevated LPS-induced bacterial translocation was even more elevated in mice fed liquid diet but was somewhat decreased in mice fed lyophilized diet. Thus, the modulatory effects of these liquid diets on the cecal flora and the incidence of bacterial translocation appeared to depend on the composition of the diet and on prior treatment with parenteral LPS.