Discovering Prebiotics: FIBER AND BEYOND

The role of probiotics in maintaining health no longer is quite as obscure to Americans as it once was. Yogurt is touted in TV and print advertisements; sometimes, an actor on a show even will play up his or her fondness for yogurt to make a fictional character more human and personable. Similarly, probiotics no longer are found only in health food stores—most drugstores sell at least two or three brands. This situation certainly is an improvement in providing sources of support for digestive health. However, it also may be a bit misleading.

The greatest benefits in probiotic clinical and other trials usually are found in those cases in which probiotics are consumed in conjunction with foods and supplements that promote their growth, which is to say, with prebiotics. There even is a term for these beneficial combinations: synbiotics. Moreover, it is not at all certain that the probiotic bacteria always constitute the more important side of this equation.

What Are Prebiotics?
Probiotics are bacteria that potentially improve health by means of their actions in the alimentary canal. Among other effects, prebiotics selectively stimulate the growth of probiotics.¹ At the very least, this suggests that prebiotics are possible solutions to the factors in our diets and habits that harm probiotics.

Prebiotics for the most part fall into the following four types:

• Non-digestible fibers
• Resistant starches and sugars
• Bacterial metabolites
• Other prebiotics, e.g., glucosamine

Prebiotics might be thought of as being the opposite of factors that harm probiotics. Unfortunately, our modern lives are full of the latter—a great many everyday items harm beneficial bacteria in the gut and promote the growth of pathogens and yeasts. Antibiotics, sex hormones (birth control pills) and antacids all exhibit unfavorable effects upon probiotic organisms.

Of course, poor dietary habits generally are the primary hindrance to the health of probiotic species of bacteria. Sugar and other refined carbohydrates tend to promote the growth of yeasts while failing to provide food to probiotic flora. Long ago, it was established that sucrose and fructose, which are major components of the American diet, have an undesirable impact upon immune functioning. Part of this effect may be indirect via actions upon the gut flora. Moreover, caution must be exercised in unlikely places. Unless care is exercised in purchasing only organically-grown meats and poultry, and, likewise, in consuming deep-ocean fish instead of the farm-raised varieties, individuals will find that they are ingesting antibiotics at the dinner table.

The First Prebiotics in Humans
Our initial exposure to prebiotics literally is with our mother's milk. Researchers have found that the development of intestinal microflora in newborns is strictly related to their early feeding. Breastfed infants, unlike the bottle-fed ones, have an intestinal ecosystem characterized by a strong prevalence of bifidobacteria and lactobacilli. This is because among the numerous substances present in human milk, oligosaccharides have a clear prebiotic effect. Indeed, oligosaccharides are quantitatively one of the main components of human milk. These compounds are only partially digested in the small intestine and a significant fraction of the amount ingested reaches the colon and selectively stimulates the development of bifidobacterial flora.²

Mother's milk might be thought of as our earliest exposure to non-digestible fiber. Human milk oligosaccharides play an important role, as prebiotic soluble fibers, in the postnatal development of the intestinal flora. In contrast, infant formulas are virtually free of prebiotic oligosaccharides. As a consequence, formula-fed infants develop an intestinal flora significantly different to the flora of breastfed infants. However, it is possible to remedy some of the downside of formula feeding. A prebiotic mixture containing 90 percent short-chain galacto-oligosaccharides and 10 percent long-chain fructo-oligosacchrides simulates naturally present prebiotics. With this prebiotic mixture, the growth of bifidobacteria and lactobacilli can be stimulated, the faecal pH can be decreased, and the presence of pathogens can be reduced to levels similar to those of breastfed infants.³

Technically, mother's milk contains human-derived glycans that inhibit pathogen binding to the gut wall. In fact, oligosaccharides are the third largest component of human milk. Oligosaccharide protection against infectious agents may result in part from their prebiotic characteristics, but is thought to be primarily due to their inhibition of pathogen binding to host cell ligands. This suggests that human milk oligosaccharides are constituents of a human milk innate immune system passed from mother to child and able to inhibit binding and disease by specific pathogens.⁴

Human milk illustrates clearly that prebiotics can play many roles at once, for example, influencing the intestinal flora while at the same time inhibiting pathogenic bacteria directly. Both probiotics and prebiotics may be helpful in malnutrition, particularly in lactose intolerance and calcium absorption, and in constipation. As in the very young, probiotics and prebiotics have been shown clearly to boost immunity in the elderly, but the clinical significance of this remains to be clarified.⁵

Each of the various types of prebiotics brings with it its own set of strengths. Once again, the broad general categories of prebiotics are:

• Non-digestible fibers
• Resistant starches and sugars
• Bacterial metabolites
• Other prebiotics

Non-digestible Fiber Prebiotics
This group of prebiotics includes oligosaccharides, gums, etc., many of which the reader will recognize. These are the most common prebiotics added to supplements and foods.

• inulin (from chicory and other sources)
• oligofructose (a mixture of fermentable fructanes)
• fructooligosaccharides (FOS, from beets and other sources)
• konjac glucomannan, acid-hydrolyzed glucomannan, galactooligosaccharides and related compounds
• high-viscosity barley beta-glucan, probably via polymerized oligosaccharides
• arabinogalactans, sometimes derived from larch trees, are densely branched, high molecular weight, water soluble polysaccharides fermented by B. longum, mostly in the large intestine; may have immune effects

Mannan Oligosaccharides as Prebiotics
It already has been noted that some of the oligosaccharides found in mother's milk can exert direct immune-related effects that can be characterized also as prebiotic. More generally, inhibiting pathogen binding or attachment is important and can have prebiotic functions. Mannan oligosaccharides (MOS) contain cell wall fragments obtained from the yeast Saccharomyces cerevisiae. Yeast cells are fractured (lysed) and the resulting culture is centrifuged to concentrate mannan oligosaccharides (bound or unbound to proteins) along with beta-glucans (a type of fiber). The components then are washed and spray dried.

Mannans have specific structures that are recognized by immune cells. Many pathogenic (gram-negative) bacteria attach to the intestinal wall surface (epithelium) using mannose-specific attachments. MOS provides competitive binding sites for these intestinal pathogens, which is to say that the pathogens attach to the MOS rather than to the intestinal wall surface and pass through the gut and leave the intestine without attaching to the intestinal wall. Mannan oligosaccharides may also enhance health by stimulating antibody production or by affecting other intestinal functions.

Fructooligosaccharides: A Downside?
Oligosaccharides and resistant starches seem to improve the uptake of calcium and magnesium. Whether all members of these categories are protective remains an open issue. For instance, on the one hand, in the case of FOS and short-chain inulin, at least, intestinal vulnerability to salmonella may sometimes be increased. On the other hand, lactulose and also the symbiotic combination of bifidobacteria plus transgalactosylated oligosaccharides have been shown to improve resistance to salmonella.

Resistant Starches and Sugars
In Europe more than in the U.S., there is a movement towards using resistant starches (RS) in foods in some proportion in substitution for normal starches. Resistant starches, as the name suggests, resist or slow digestion, usually by resisting the actions of the starch digestant amylase found in the saliva and throughout the upper digestive tract. The component amylose resists being broken down by amylase to more simple sugars and then to glucose. High amylose starches can be derived from corn, rice, barley, soybean and other sources.

RS exerts its synbiotic action partly through the adhesion of bacteria to its surface. As one example, rice porridge high in RS appears to modify large-bowel microflora favorably by lowering Escherichia coli and coliform numbers, in this acting a bit like the MOS described above. Another mechanism of action is changing the pH of the gut to make it more acid. Many of the beneficial effects of RS on large-bowel function appear to be exerted through short-chain fatty acids (SCFAs) formed by bacterial fermentation. The presence of SCFAs indicates a lower pH and these acids themselves may support normal gut wall health.

In a nutshell, human colonic bacteria ferment RS and non-starch polysaccharides to short-chain fatty acids, mainly acetate, propionate, and butyrate. SCFAs stimulate colonic blood flow and fluid and electrolyte uptake. Butyrate is a preferred substrate for colonocytes (large intestine gut wall cells) and appears to promote a normal phenotype in these cells. The fermentation of some RS types especially favors butyrate production and bile turnover.

Bacterial Metabolites as Prebiotics
There is an argument to be made that many of the benefits of yogurt, sauerkraut, kimchee and other fermented foods do not depend upon the fermentation bacteria ever going beyond the stomach. Instead, it is the many metabolites or fermentation products found in these foods that are important. Processing that sterilizes these products often will destroy the significant metabolites and, of course, the production of “faux” cheeses, yogurts, etc. usually means that the metabolites are never formed.

A good example of the effects of bacterial metabolites is Metabolin^TM a special blend of fermentation products prepared from selected strains of lactic acid bacteria, such as Propionibacterium shermani ssp. and Lactobacillus ssp. These bacteria produce natural organic acids and peptides that are instrumental in suppressing undesirable microorganisms. Inhibitory organic acids found in the product include propionic, acetic and lactic acids. The combination of natural acetic, propionic and lactic acid can effectively inhibit the growth of common gram-negative bacteria, yeast and molds. Peptides produced by lactic acid fermentation are known to be inhibitory substances to many types of bacteria. The same principles apply to Germinated Barley Foodstuff (GBF), a prebiotic that has shown promise in irritable bowel disease (IBD) and ulcerative colitis.

Other Prebiotics
As might be expected, there are a number of prebiotics that defy easy classification, yet nevertheless can yield significant benefits. For instance, most species of bifidobacterium (found mostly in the large intestine) can ferment D-galactosamine, D-glucosamine, amylose and amylopectin. Some of these are "amino sugars" better known for joint than gut health. Nevertheless, N-acetyl-glucosamine (NAG) has long been used in Europe for IBD and other similar conditions (1.5–3 grams per day in divided dose). Its prebiotic effect may be a part of its benefit.

Wild Bitter Melon—a Natural Prebiotic
Good prebiotics are continuing to be discovered, although it may not always be clear whether their effects reflect a combination of components already known or something new. A previous essay [in Total Health magazine Online October 2011], "Going WILD with Bitter Melon for Blood Sugar Support," examined a number of the benefits of bitter melon and the superiority of a specially stabilized wild variety (Glycostat®) exhibited in comparative animal trials conducted both in Indian and in the United States at Georgetown University Medical Center.⁶ Since that time, researchers at China Medical University (Taiwan) conducted a quite different set of trials with Glycostat to examine its usefulness as a prebiotic and potentially as an anti-obesity agent as part of a prebiotic/probiotic combination. As the researchers put it, "the active ingredients of . . . [a probiotic/prebiotic] compound formula will have the actions of coordination, competition and inhibition, leading to the augmentation, attenuation or even ineffectiveness." In other words, probiotics are commonly bundled together with many other ingredients, some of which are good choices and some of which are bad choices and only direct experimentation can clarify the issue.

In this case, two types of experiments were conducted. In the first test, which was in vitro, a special strain of bacteria, Lactobacillus plantarum CMU995, was shown to be resistant to acid and bile salts, and effective at adhering to a simulated gut wall, something important for establishing adequate residence time in the gut to exhibit benefits. As part of the in vitro testing, experimenters further determined that many extracts, such as green tea extract and aloe vera extract, inhibited the growth of lactic acid bacteria, whereas Glycostat did not. In fact, CMU995 could be mixed with Glycostat powder and was relatively stable at even 25°C conditions.⁷ Related tests showed that Glycostat exhibits a similar growth-promoting effect upon a wide number of lactic acid and other probiotic bacteria, a finding that suggests that this wild bitter melon ingredient may have broad symbiotic potential.

The second study was in vivo with mice on a high fat diet. There was an active arm, a control arm and an arm testing two percent cholestyramine (a cholesterol-lowering drug). Under test conditions, the drug lowered cholesterol 36.2 percent, the combination prebiotic/probiotic by 30.8 percent, and the probiotic alone by 26.6 percent. The combination increased the viable count of the lactic acid bacteria in the intestinal tract of the mice as well as reducing the concentration of triglyceride and leptin in the blood. There was a dramatic decrease in fat tissue weight and cell size at six weeks, the combination of prebiotic/probiotic being superior to all other arms.⁸

Conclusion
The exploration of the concept of synbiotics, meaning prebiotic/probiotic combinations with special benefits, is beginning to yield results not originally anticipated based solely on research with probiotics. The role of prebiotics remains much under appreciated by most Americans, who, if they desire to experience greater benefits from their probiotic supplements should experiment with the various prebiotic categories. Finally, as in the case of wild bitter melon, some items already recognized as having health benefits may exhibit more or other unexpected benefits if utilized as prebiotics in symbiotic combinations.

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