Probiotics 1

Continued from Probiotics and Prebiotics As Ingredients in Functional Foods

In total, 109 volunteers actually ingested different amounts of chicory inulin and/or oligofructose.  The effect was seen as soon as within 1 week after the start of the ingestion, and was demonstrated to last for more than 2 months.  A number of studies also included a certain run-out period, during which the bifidobacteria levels always started to decrease, and the composition seems to return to its original or pre-study status.  Again this is a clear demonstration that the increase is purely related to the ingestion of the active ingredient.  One study (Menne et al, 2000) contained 2 different daily diets through which 8 g of oligofructose was ingested, suggesting that the food matrix that contains the prebiotic ingredient does not have any influence on the effect.  The prebiotic effect seen with inulin and oligofructose has been demonstrated in healthy volunteers as well as in patient groups of various disease states (constipation, inflammatory bowel diseases, colonic cancer, etc.) over various age groups (infants, children, adults and elderly person) and living in different places all over the world (Tuohy et al, 2001a & b; Rao, 2001; Menne et al., 2000; Roberfroid et al.,1998; Gibson et al, 1995; Bouhnik et al, 2004).

From these randomized, double-blind and placebo-controlled intervention studies it is demonstrated that the prebiotic effect with inulin and oligofructose is obtained as soon as within 1 week after the start of consumption and already at a quantity as low as 5 g/day (Rao, 2001).  In this perspective inulin and oligofructose optimalize gut health.

In preterm and a terme born infants, most studies are done on the prebiotic effects of a combination of GOS and long chain inulin which clearly prove a modulation of the bacterial flora towards a composition more closely related to that of the colon in the breast-fed infant.  This is particularly important since breast-fed infants have a colon flora dominated by bifidobacteria that is considered to be in relation with the lower prevalence of disease within this group of infants.  Infants fed infant formula supplemented with GOS and long chain inulin showed to have a colonic environment (lactic acid, short chain fatty acid profiles and pH) and stool characteristics more closely related to breast fed infants (Knol et al., 2005; Schmelzle et al., 2003; Boehm et al., 2002; Moro et al., 2002).

Bacteria that inhabit the colon can be divided into: those that are free living in the lumen (planktonic bacteria) and those that are attached to the mucosa (or the mucosa-associated flora:  MAF).  The planktonic flora is known to play a. o. a major role in the digestion process through fermentation and the provision of a barrier to invading pathogens. Less is known about the MAF population, but more recent evidence on the prebiotic effect of a combination of oligofructose and long chain inulin shows that these ingredients also alter the balance of these MAF populations towards a more beneficial composition (e.g. increased numbers of bifidobacteria and lactobacilli). (Langlands et al.; 2004).  In this recent study, the influence on inulin and oligofructose specifically in the MAF was monitored in 14 subjects recruited from colonoscopy waiting lists.  During a 2 week supplementation of 15g of a carefully selected inulin and oligofructose mixture, a significant increase was observed for both bifidobacteria and lactobacilli.  Because of their intimate association with the epithelial cells, the MAF is directly involved in the functioning of the epithelia through its ability to exclude pathogens (increase colonization resistance), act on the immune system because of cross-talk between bacteria and the epithelial cells (immuno-modulation) and moderate inflammatory responses in state of disease (inflammatory bowel disease).  This increase in intestinal defense against pathogens by inulin and oligofructose has been demonstrated in-vitro (Wang & Gibson, 1993; Gibson & Wang 1994), animal models (Buddington et al., 2002; Bomba et al., 2002) and human intervention trials (Lewis et al., 2005).  In this perspective inulin and oligofructose contribute to improved epithelial health and increase the resistance against infections.  Consequently these ingredients can be efficiently used to decrease gastrointestinal discomfort e.g. traveler’s (Cummings et al., 2001) and antibiotic associated diarrhea (Lewis et al., 2005)

Recently a study in infants showed also benefits of inulin and oligofructose on systemic infections in that infants supplemented with oligofructose (2 g/d) had a decrease in the number of sickness events and related symptoms (vomiting, diarrhea, etc.). (Waligora et al., submitted for publication)

In addition, depending on the chain length of the inulin-type fructans the prebiotic effect can be extended throughout the whole colon.  Studies have demonstrated that oligofructose is more rapidly fermented in the proximal colon, whereas the longer inulin chains allow a slower fermentation reaching the more distal parts of the colon.  In this perspective a ‘second generation prebiotic’ is developed and commercialized that contains oligofructose and long chain inulin in a patented combination (oligofructose-enriched inulin named Synergy1) to exert a sustained prebiotic effect throughout the whole colon (Van Loo, 2004, Langlands et al., 2004).

A prebiotic effect that takes place in the more distal parts of the colon is of particular importance since this is the part where most diseases occur (e.g. colorectal cancers).  The distal colon is an environment dominated by protein fermentation, which generates indoles, p-cresol, ammonia and other metabolites with toxic effects.  The oligofructose-enriched inulin is able to revert this proteolytic into a saccharolytic environment decreasing the risk of developing disease.  This effect has been demonstrated in placebo-controlled human intervention trials where volunteers consuming the oligofructose-enriched inulin had a lower urinary exertion of nitrogen vs. controls (data from the GBOU-project, 2005).

Recent data from the SYNCAN project on the effect of a synbiotic with oligofructose-enriched inulin on colon cancer patients and patients with high risk for developing cancer (polyp-ectomized patients) indicated a clear preventive action of the synbiotic on the development of colorectal cancer in both patient groups. (Van Loo et al., 2005)  The effects of Synergy1 alone in the prevention of cancer have been demonstrated before in vitro (Klinder et al., 2004a and b) and in various animal models (Femia et al., 2002, Roller et al., 2004a and b) and on various types of cancer (intestinal proximal and distal parts and extra-intestinal sites). (Taper et al., 1997 and 1998 and 1999)

In patients with sustained and chronic inflammations such as inflammatory bowel diseases (ulcerative colitis and Chrohn’s disease) the benefits of supplementation with inulin and oligofructose alone or in a symbiotic combination together with current medical therapies have been demonstrated with respect to the clinical outcomes of disease (including histological appearance of the inflamed tissue) and modulation of parameters involved in the inflammatory process (human beta defensins mRNA expression, cytokine profiles, calprotectin, dendritic cells). (Furrie et al., 2005; Bosscher et al., 2005; Lindsay et al, 2005)

Extensive research on the use of inulin and oligofructose has been done on their role in calcium and magnesium metabolism.  One study (double-blind and placebo-controlled) in boys showed a significant increase in the calcium absorption, measured by stable isotopes, with 15g/d of oligofructose vs. the control group (Van den Heuvel et al., 1999).  In addition, 3 randomized double-blind and placebo-controlled studies on the effects of Synergy1 in adolescents demonstrated that an increase in calcium absorption was obtained by 20% after Synergy1 intake at a daily dose of 8g vs. controls (maltodextrin) (Griffin et al., 2002 and 2003).  More recently data from a long-term study (1 year) showed that this higher calcium uptake led to a significant increase of bone mineral density and bone mineral content, which was not observed in the control group.  Increasing peak bone mass during adolescence is one strategy to combat the increasing prevalence of osteoporosis all around the world.  In this perspective inulin and oligofructose, and more efficiently Synergy1, improve bone health (Abrams et al., 2005).

Research on inulin and oligofructose is extending these days towards the modulation of gut hormones that act on the gut-brain axis that involves the signaling of the feeling of hunger vs. satiety.  It appears that the rapid fermentation of oligofructose induces the release of gut hormones such as GLP-1 and reduces plasma levels of ghrelin (Cani et al., 2004).  In continuation with the data from animal studies a pilot study in human volunteers is currently in the press. (Cani et al., in press).  In addition, inulin and oligofructose have an impact on lipid metabolism (Fiordaliso et al., 1995; Daubioul et al., 2002) and modulate triglycerides and cholesterol levels in plasma (Letexier et al., 2003; Jackson et al., 1999)  In this way inulin and oligofructose are promising agents in the search for strategies to prevent or treat obesity and related chronic diseases such as diabetes and cardiovascular disease.