Inulintype Fructans And Systemic Defense Functions

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Besides their effect (both direct and indirect) on the risk of diseases related to dysfunction of the gastrointestinal defense, inulin-type fructans have also been shown to possibly contribute to reducing the risk of diseases related to dysfunction of systemic defense. Essentially, this has been shown using experimental models of:

1. Systemic infection

2. Chemically induced mammary carcinogenesis

3. Growth of implanted tumor

4. Metastasis

5. Cancer therapy

12.5.1 Effect of Inulin-Type Fructans on Risk of Systemic Infection

In a recent study, Buddington et al. have demonstrated a strong protection against a systemic (intraperitoneal) challenge by Listeria monocytogenes (1-5 □ 106 cfu/mouse) and Salmonella typhimurium (103 cfu/mouse) in mice (B6C3F1, n = 25) prefed with either oligofructose or inulin HP (10% w/w in diet) for 6 weeks.137 Indeed, 2 weeks after the challenge, survival in the L. monocytogenes and S. typhimurium infected mice were 72% and 16%; 88% and 24%; 100% and 40% in the groups receiving the standard, the oligofructose (NS and +16%) or the inulin (+24% and +28%) diet, respectively. The protective effects of inulin and to a lesser extent oligofructose was correlated with a higher density of lactic acid bacteria in the intestine, an increased phagocytic activity of unactivated peritoneal macrophages, a heightened sensitivity of lymphocytes, and enhanced natural killer cell activity of splenocytes.

12.5.2 Effect of Inulin-Type Fructans on Risk of Chemically Induced Mammary Carcinogenesis

Only one preliminary experiment has been reported on the effect of oligofructose on chemically induced mammary carcinogenesis in rats. In that experiment, young (45 days of age) female Sprague-Dawley rats (n = 8) were injected s.c. with 50 mg/kg bw. of N-methylnitrosourea. One week later they were fed a standard diet either without or with oligofructose (15% w/w).251 From week 4 after the injection of the carcinogen until week 26, number and position of mammary tumors were manually assessed and their volume was evaluated weekly by measuring three perpendicular dimensions. At week 27 rats were sacrificed and a detailed autopsy was performed with tumor counting, measuring, and histological examination. All along the observation period (week 4 to week 26) data show that the incidence of tumors as expressed by the number of rats bearing tumors was always lower in the oligofructose-treated than in the control rats (e.g., 25% vs. 50% and 62.5% vs. 90% at weeks 12 and 24, respectively). Similarly, the total yield of tumors (number of tumors per group) in the oligofructose fed group was lower than in the control group (e.g., 2 vs. 7 and 9 vs. 16 at weeks 12 and 24, respectively). As revealed by histological examination, all mammary tumors were adenocarcinomas and, in the rats fed the control but not the oligofructose diet, two renal fibrosarcomas and two metastases (one in the lung, one in lymphatic node) were detected. Oligofructose feeding had, however, no effect on mean mammary tumor volume. These data are consistent with the hypothesis that oligofructose has the capacity to negatively modulate the carcinogenic process by slowing down the kinetics of appearance of malignant tumors and by reducing the risk of metastasis. But these data need to be confirmed using a larger number of animals group and comparing oligofructose with long-chain inulin and/or oligofructose-enriched inulin Synergy 1.

12.5.3 Effect of Inulin-Type Fructans on Growth of Implanted Tumors

As indirect evidence for enhanced systemic defense functions, experimental studies have also been designed to test for the possible effect of dietary inulin and oligofructose on the growth of transplantable mouse tumors. Essentially three different tumor cell lines have been used, i.e., the mammary tumor cell line EMT6,252 the transplantable liver tumor cell line TLT253 254 and the B16F10 tumor cell line. In the first two protocols, the diets containing oligofructose or inulin (15% w/w) were introduced 7 d before an intramuscular transplantation of either EMT6 tumor cells into balb/e female mice or TLT tumor cells into young male NMRI mice. Two perpendicular tumor dimensions were measured weekly and the increase in the mean tumor surface was calculated for each time period for the different groups of control and treated animals. These experiments demonstrated that the in vivo the growth of both tumor cell lines was significantly (ANOVA p < 0.01) and similarly inhibited by both oligofructose and inulin that had basically the same effect (see Figure 12.3).251,255

Untreated

Oligofructose

Inulin r

10 12 14 16 18 20 Days after tumor transplantation

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