The most widely recognized living probiotic bacteria in use today are lactobacilli and bifidobacteria (Macfarlane and Cummings 1999). These bacteria occur naturally in the human GI tract. Figure 1 shows images of these bacteria magnified many times under a microscope.
These and other live bacteria are available in a range of food products targeted to various age groups.

Consumption of probiotics can increase the levels of beneficial bacteria in the gut, creating an environment that is unfavorable to the growth of harmful bacteria (Parracho et al 2007). Increased levels of beneficial bacteria that result from consumption of probiotics can also support immune function (Rolfe 2000).

Although conclusive evidence about the health effects of probiotics is limited, researchers are actively pursuing studies on their usefulness in the prevention and treatment of a number of disorders (Rolfe 2000). These include:

• antibiotic-induced diarrhea
• traveler's diarrhea
• gastroenteritis due to H. pylori bacteria
• pouchitis
• irritable bowel syndrome

Currently, most of the data on probiotics in infant feeding are based on small trials. Additional studies are needed to identify potential clinical benefits and tolerability of probiotics added to infant formula (Osborn and Sinn 2007).

Because they are live bacteria, probiotics are sensitive to heat, moisture, oxygen, and acid (Douglas and Sanders 2008). Keeping probiotics alive during food processing, packaging, and storage is a technological challenge. Manufacturers of probiotic foods and supplements have developed numerous technologies to control temperature, moisture, and oxygen. Once a package is opened, however, these controls are compromised. Added to these challenges are the deleterious effects of the stomach's acidic environment on the survival of probiotic bacteria.

Scientists have defined prebiotics as a selectively fermented ingredient that allows specific changes, both in the composition and/or activity in the gastrointestinal microflora that confers benefits upon host well-being and health (Roberfroid 2007).

Many prebiotics identified to date are members of the carbohydrate family. One of the things that distinguish prebiotics from other, more familiar carbohydrates found in foods (eg, sugars, starches) is that humans cannot digest prebiotic carbohydrates very well.

Before going into greater detail about prebiotic carbohydrates, take a moment to review some of what you may already know about other carbohydrates, especially lactose and sucrose. This information will make it easier to understand and remember that the prebiotics that you are learning about here are simply members of the carbohydrate family.

Lactose is the primary sugar in milk, and is a disaccharide. This means that it is a carbohydrate that is made up of 2 connected sugar units (di- = two; saccharide = sugar). Each of the individual sugar units in a disaccharide is referred to as a monosaccharide (mono- = one). Figure 2 illustrates this basic concept. As mentioned, lactose is a disaccharide. It is made up of 1 galactose unit bonded to 1 glucose unit. This basic structure is shown in Figure 3. Another disaccharide that we are all familiar with is sucrose, or table sugar. Sucrose is made up of 1 fructose unit bonded to 1 glucose unit. This basic structure is shown in Figure 4. Disaccharides such as lactose and sucrose can be digested by most people. Enzymes in the GI tract break the chemical bond between the sugar units, releasing the monosaccharides, which can then be absorbed by the body in the small intestine. This process is illustrated in Figure 5.

In addition to digestible carbohydrates used by humans for energy, a variety of poorly digested carbohydrates are contained in fruits, vegetables, and other plant foods. In general, humans do not have the necessary enzymes to break down these specific types of carbohydrates into smaller pieces that can be absorbed by the gut (Gibson and Roberfroid 1995).

Since these carbohydrates are poorly digested, they are available as a source of fuel for the beneficial bacteria in the large bowel (Roberfroid 2007). Examples of nondigestible, prebiotic carbohydrates that occur naturally in foods include the oligosaccharides (oligo- = a few) known as galacto-oligosaccharide ( GOS) and fructo-oligosaccaride (FOS).

GOS is an abbreviation for galacto-oligosaccharide. GOS refers to a group of compounds containing chains of galactose units with lactose on the terminal end. The length of the galactose chain in GOS varies from 1 to approximately 6 units.

Figure 6 illustrates the basic structure of GOS. The linkages between the galactose units are primarily β(1-4), but some of the linkages are β(1-2) and others are β(1-6). Lactase, the enzyme in the human GI tract that breaks down lactose into galactose and glucose monosaccharides, is not able to break the linkages between the monosaccharides in GOS. This is why GOS is poorly digested, while lactose, which is a part of GOS, is easily digested by many people.

GOS can be found in human breast milk (Coppa et al 1999). It can also be manufactured through the enzymatic processing of lactose for use as a food ingredient (Macfarlane et al 2006).

Human milk contains a diverse array of oligosaccharides, including GOS. Collectively, the oligosaccharides in breast milk are called human milk oligosaccharides (HMOs). In contrast to human milk, cow's milk contains very small amounts of oligosaccharides (Boehm and Stahl 2007). HMOs have been shown to be an important factor in stimulating the growth and activity of beneficial bacteria in the GI tract of the breastfed infant (Coppa et al 2004).

The primary action of prebiotics is to stimulate the growth of beneficial bacteria that are already present in the GI tract. As described in Figure 9, prebiotics are poorly digested in the upper GI tract (stomach and small bowel). As a result, prebiotics pass into the large bowel, where they are available as a food source for beneficial bacteria. This results in increased levels of beneficial, or "good," bacteria, which helps to create an environment that is unfavorable to the growth of "bad" bacteria.

The increased levels of beneficial bacteria in the gut resulting from the consumption of prebiotics are associated with a number of positive effects in the digestive and immune systems (Figure 10). These include the development of the mucosal barrier, production of short-chain fatty acids which reduce pH in the gut, activation of the immune system, metabolism of bile acids, and synthesis of several vitamins (Bruzzese et al 2006). The GI and immune effects resulting from increased beneficial bacteria in the gut are especially important during infancy.

The human body is home to an abundance of bacteria. This is especially true in the GI tract, which contains as many as 500 different types of bacteria. You may be shocked to learn that bacteria account for 60% of the weight of your feces (Guarner and Malagelada 2003)!

The bacteria in your GI tract are often referred to as commensal bacteria, meaning that they live in peaceful coexistence with you. Some of the bacteria in your gut are called symbiotic bacteria. This is because both you and the bacteria benefit from the other's presence. You provide food and shelter for the symbiotic bacteria. In turn, the symbiotic bacteria help you in many ways (Gibson and Roberfroid 1995; Bruzzese 2006), including the following:

• Digestion of unused energy sources
• Prevention of growth of harmful bacteria
• Synthesis of certain vitamins
• Healthy development of the GI tract
• Support of the developing infant immune system

As most of us know, the human gut can also contain potentially harmful bacteria, such as Clostridium difficile and Escherichia coli. However, these bacteria are not present in large numbers in healthy individuals. Prebiotics help discourage the growth and activity of less favorable bacteria by selectively increasing the number of beneficial bacteria.

The bacterial composition in the infant digestive tract (also called the intestinal microflora) follows a pattern of change starting in the newborn, and varies depending on the infant diet. Development of the infant's intestinal microflora is initiated at birth. The aseptic, or sterile, digestive tract of the fetus is inoculated with bacteria during birth by the mother's intestinal and vaginal microflora.

During the first week of life, enterobacteria and enterococci predominate in the gut of both breastfed and formula-fed infants. After this, the microflora changes rapidly. Some of the changes that occur depend on whether the infant is breastfed or formula-fed (Orrhage and Nord 1999; Harmsen et al 2000).

In general, breastfed infants have been shown to have higher levels of bifidobacteria than formula-fed infants (Orrhage and Nord 1999). The increased presence of these beneficial bacteria is at least partly due to substances found in human breast milk, especially the HMOs (Coppa et al 2004).

The intestinal microflora of the formula-fed infant differs from that of the breastfed infant (Harmsen et al 2000). While human milk-fed infants have an abundance of bifidobacteria in the gut, formula-fed infants have a more diverse gut flora, similar to that seen in adults.

The addition of prebiotics to infant formula can increase beneficial bacteria in the digestive system to levels similar to those in the breastfed baby (Ben et al 2004). In addition, prebiotics can help soften stools to be more like those of the breastfed infant (Costalos et al 2008; Ben et al 2004; Moro et al 2002). Recent clinical studies also suggest that prebiotics may have the potential to reduce the risk of common childhood infections (Bruzzese et al 2006, abstract; Arslanoglu et al 2007) and the incidence of atopic dermatitis (Moro et al 2006).

Prebiotics stimulate the growth of beneficial bacteria in the gut. In a recent clinical trial, formula-fed infants were randomized to receive either an infant formula with prebiotics (GOS at 2.4 g/L) or an infant formula without prebiotics (control formula). When compared with infants fed a control formula, infants fed a formula containing prebiotics had significantly increased levels of bifidobacteria and lactobacilli, more closely resembling levels in the breastfed infant (Ben et al 2004).

Infant formulas containing prebiotics can help soften stools to be more like those of breastfed infants (Costalos et al 2008; Ben et al 2004; Moro et al 2002). In a recent study, healthy formula-fed infants 0 to 14 days after birth received either a formula with prebiotics (GOS-inulin mixture at 4 g/L) or a standard formula without prebiotics (Costalos et al 2008). Infants fed the prebiotic formula had significantly softer stools than infants fed the control formula. Other studies have shown similar effects of prebiotic formulas on stool softness (Ben et al 2004; Moro et al 2002). Thus, clinical studies indicate that the addition of prebiotics to infant formula results in softer stools that are more like those of breastfed infants.

It has long been thought that infant nutrition may play a role in the prevention of certain infections. A clinical study randomized healthy infants, between 15 and 120 days of age, to receive a standard infant formula with prebiotics (GOS-inulin mixture in a 9-to-1 ratio) or an infant formula without prebiotics (Bruzzese et al 2006, abstract). After 3, 6, 9, and 12 months, data on episodes of respiratory tract infections were collected. The number of babies with at least 3 episodes of upper respiratory tract infection was significantly lower in the group receiving the formula with prebiotics than in the group receiving the control formula (Bruzzese et al 2006, abstract).

Many infants and children suffer from allergies. Atopic dermatitis is also known as eczema. It is an allergic disease characterized by dry, itchy skin. Preliminary evidence suggests that some allergic disease might be prevented if the gut immune system in infants is properly developed (Kukkonen et al 2007).

In a recent study, infants at high risk of developing allergic diseases such as atopic dermatitis were randomized to receive a hypoallergenic infant formula with prebiotics (8 g/L GOS-inulin mixture in a 9-to-1 ratio) or a control formula without prebiotics (Moro et al 2006). This study showed that compared with the control formula, the formula with prebiotics reduced the incidence of atopic dermatitis.

Note: The clinical studies summarized in this section are not Abbott sponsored; research was not conducted for Abbott products.

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