Prebiotics

Prebiotics are non-digestible food components, mostly - but not exclusively - constituting of dietary fibers, which promote the growth and activity of bacteria in the large intestine. In the diet are present in minimally processed and unprocessed plant foods. For example, chicory, artichoke, Jerusalem artichoke, onion, asparagus and the skins of apples and oranges naturally contain considerable amounts of prebiotically active substances (1). Inulin, is added to fat-reduced yoghurts and helps to improve taste, texture and mouthfeel. In sausage products, inulin increases fiber content. Pectins, which serve the food industry as gelling, thickening and stabilizing agents and are contained buried in jams, sweets, bakery products and dairy products (1). 

The bacterial flora of the gastrointestinal tract consists of an enormous variety of organisms, which together form a complex microcosm that significantly influences both the health and the disease of the host on many levels. The fact that the genome of intestinal bacteria contains about 150 times as many genes as our own demonstrates the importance and influence of this system. But it is precisely this capacity and diversity that makes it difficult for science to grasp the full extent of the effect. In addition, no two microbiota are alike. Even if at least those of closely related family members are similar in essence, external influences such as stress, nutrition or drug intake are the main factors that determine the activity and composition of the individual intestinal flora. Thus, the care of intestinal bacteria is highly individual. Nevertheless, scientists  are attempting to get a global overview of the functions and connections of the microbiome with human metabolism in order to get an impression of the actual influence on the health status. The cultivation of some microorganisms is difficult, which in turn limits research. New methods for sequencing the bacterial genome and metagenomic analyses provide the possibilities and information needed to understand the human microbiome. These findings have demonstrated how important the balance of intestinal bacteria really is and that dysbioses very often correlate with the occurrence of serious diseases. This is now the basis for the development of medical products that modulate microbial diversity and thus have a health-promoting effect on the body. Such a change can, for example, increase or decrease the synthesis of health-relevant bacterial metabolites, reduce intestinal pathogens, stimulate the immune system or stimulate the growth of health-promoting bacterial strains (4)(5).

One of the main tasks of intestinal bacteria is to break down carbohydrates that have not been digested in the ileum. The so-called carbohydrate fermentation primarily leads to the formation of short chain fatty acids (SCFAs), such as acetates, propionates and butyrates, which can be quickly absorbed and introduced into the energy metabolism. Humans draw up to 10 % of their total energy needs from this process, but the actual extent depends strongly on the individual composition of the microbiota. Thus, modulation of the intestinal flora can also contribute significantly to energy production, storage and consumption (4). SCFAs are absorbed by the mucosa of caeca and ascending colon. The mucosa cells themselves benefit above all from the butyrates, which contribute, among other things, to the maintenance of their structure. Butyrates can inhibit the enzyme histone deacetylase and thus alter gene expression in the epithelial cells of the colon. However, they can also intervene in the inflammatory response. By inhibiting the nuclear factor κB (NFκB) and the interferon(IF)-γ production, butyrates have an anti-inflammatory effect (6).

Non-digested carbohydrates also contribute to stool consistency in the colon and increase stool mass. More weight causes a higher defecation frequency and a shorter transit time. This in turn can prevent colon diseases such as constipation, diverticulitis and colon cancer. Most non-absorbed carbohydrates also have a laxative effect by increasing osmotic effects and binding water to remaining unfermented fibers. In summary, it is evident that both a healthy composition and feeding of intestinal bacteria are nutritionally and clinically highly relevant and can influence our long-term and short-term well-being to a large extent (7).
 

Finding a suitable and holistic description of dietary fibers has so far been more difficult than assumed. The large variety of structures and properties of the components in question complicates the classification. In addition, the physiological significance is greater than originally thought. It is currently agreed that dietary fibers are carbohydrate polymers that are not broken down by the secretions and enzymes of the human digestive tract. Botany also insists on the characterization of dietary fibers as plant cell wall components. The term thus covers a very broad spectrum of compounds which differ greatly in their chemical properties and structure. Examples of this are: Non-starch polysaccharides from plant cell walls, lignins, microbial polysaccharides, inulin and resistant starch (7)(8). 

The definition as cell wall components explains the primary source of dietary fiber: (almost) anything of vegetable origin. Many dietary fibers can be found in roots, tubers and other vegetables as well as in fruit, nuts and of course cereals. As cell wall constituents, dietary fibers offer stability and protection against invading organisms and must also be sufficiently dynamic to adapt quickly to growth, differentiation and environmental influences. While the cellulose provides the appropriate supporting function, the pectin content determines the porosity and thus the material exchange through the cell wall (8). Fibers are classically divided into water-soluble and water-insoluble. Both types occur in fiber-rich foods in different quantities and have specific properties. Therefore, as always, variety and versatility in the diet make sense in order to be able to benefit from the entire health-promoting spectrum of fiber (7).

The solubility of a dietary fiber determines its technical functionality and physiological suitability. Soluble dietary fibers, such as pectin increase the viscosity of the food paste in the gastrointestinal tract and reduce the glycemic response and blood cholesterol. Insoluble agents, such as cellulose and lignin, reduce intestinal transit time and increase stool frequency (7). The health-promoting properties have been scientifically confirmed: dietary fibers have been shown to reduce total and LDL cholesterol in the blood as well as postprandial blood sugar and/or insulin levels (9). The underlying mechanisms of the cholesterol-lowering effect are postulated to be changes in cholesterol absorption and bile acid reabsorption as well as modulation of liver metabolism and plasma lipoprotein clearance. In addition, there is an inverse correlation between fiber intake and the risk of developing coronary heart disease. The influence on blood sugar and insulin levels is explained by pectin-mediated delayed gastric emptying and faster onset of satiety due to slowly digestible starch. This is precisely why an increased dietary fibers intake is also discussed for the prevention of diabetes mellitus type 2 (7). Many dietary fibers are subject to fermentation by colonic bacteria. In this way they have a significant influence on their growth and activity. The stimulation of beneficial microorganisms, such as lactobacilli and bifidobacteria, in the large intestine has a positive effect on the health of the host. Solubility also plays a role here, because the extent to which dietary fibers can be fermented depends strongly on this property. For example, colon bacteria degrade soluble pectin to a much greater extent than insoluble lignin (7).

The composition of intestinal microbiota is variable. It changes over time and adapts to given and sometimes extreme circumstances. The most important external determinant of the microbiome is likely nutrition. The composition and the energy content of the diet plays an important role. Depending on an individual genetic background, what we eat every day directly influences the composition of our intestinal flora. Genetics thus provides the framework conditions that are then modulated by external influences. There are twin experiments in twins that seek to quantify the actual proportions of genetic and non-genetic factors. They teach us that the content of individual fecal microbes is at least similar in closely related individuals. The microbiota of monozygotic twins with normal body weight is more similar than that of twins with an unequal tendency to overweight (4). A high-energy diet is associated with a substantial transformation of the colon flora. For example, the number of health-promoting bifidobacteria decreases. This in turn leads to metabolic changes associated with the development of insulin resistance. In addition, a low intake of fruit and vegetables is associated with a reduced genetic diversity of the microbiota. Dietary interventions can broaden the intestinal gene spectrum again and thus positively influence possible clinical phenotypes. A diet based on a high whole grain and fibers intake has been shown to reduce endotoxin-producing opportunistic pathogens, such as enterobacteria or desulfovibrionales, and stimulate the growth of bacterial strains associated with intestinal barrier protection (4). The intestinal flora also actively determines how we react to food. A high-fiber diet during childhood can, for example, lead to a lower tendency to become overweight as an adults. In humans, the presence or frequency of certain bacterial strains can also be used to predict how overweight people react to a particular form of nutrition. This fact highlights the potential of the microbial signature for personalized nutrition. In addition to nutrition, age also plays a role in the modulation of the microbiome. However, this change is probably also due to the change in eating habits towards higher-energy and sugary foods (4).  
 

As already mentioned above, the intestinal flora produces mainly short-chain fatty acids (SCFAs) as products of prebiotic degradation. These molecules are small enough to diffuse through the intestinal erocytes and enter the bloodstream. Prebiotics can therefore not only positively influence the gastrointestinal tract, but also other distant organs or organ systems (1).
 

Fibres from acacia, also known as gum arabic, ferment slowly in the colon. It is therefore assumed that the addition of gum arabic to a dietary fiber mixture prolongs fermentation time. A variation modulation effect is expected on the microbiota in the different areas of the ascending, transverse and descending colon. The health-promoting properties of dietary fibers on colon flora should not be affected (5). The high-quality raw material Fibergum^TM provides soluble acacia fibers from a completely natural source. Obtained from the sap of carefully selected acacia trees, Fibrergum^TM guarantees a soluble fiber content of at least 90% of the total dry matter. The raw material also contains valuable polyphenols, such as catechins and epicatechins, as well as the minerals magnesium, sodium, calcium and potassium. Fibergum^TM is considered well tolerated even in high doses. Studies have confirmed bifidogenic activity and show the stimulation of lactobacteria growth with an intake of 10 g Fibergum^TM/day. The soluble acacia fibers are primarily fermented in the transverse large intestine by lactobacteria, but a portion still reaches the descending colon, which causes a gradual fermentation process. Over a longer period, the microbiota of the colon can adapt and the fermentation capacity increases. Fibergum^TM also induces the production of SCFAs. In particular, after administration of Fibergum^TM the production of butyrates in the distal colon (10) increased. An in vitro study by Marzorati et al. (2015) investigated the influence of gum arabic on the fermentation of fibre mixtures. Using the Simulator of the Human Intestinal Microbial Ecosystem (SHIME®) the natural digestive processes could be simulated and the fermentation of inulin and  fructooligosaccharides (FOS) in combination with gum arabic could be observed. Usually both FOS and inulin are fermented very rapidly, but the addition of gum arabic caused more gradual degradation. This is mainly attributed to the change in intestinal pH resulting from the individual fiber mixtures. While the control mixture (without gum arabic) only led to acidification of the ascending colon, the intervention caused an increase in pH in all sections of the colon. This suggests that parts of the dietary fiber mixture reach even the distal colon due to slower fermentation. The formation of short-chain fatty acids could be increased both with and without gum arabic. In addition, both mixtures showed bifidogenic properties. However, the modulating activity in different sections of the colon was different. It was found that long-term repeated administration was required to cause gradual changes in the composition and activity of the colonic flora. Since the additional intake of gum arabic reduces the rate of fermentation, the authors see a health-promoting effect here, which suggests the intake of larger amounts of dietary fiber (5).
 

The term resistant starch refers to the total amount of starch and starch degradation products in a food that resists degradation in the small intestine, reaches the large intestine and is then fermented by microorganisms. The content of resistant starch in a carbohydrate is influenced by various factors. These include the ratio of the two starch building blocks amylose and amylopectin. The latter represents a group of highly branched glucose polymers. Amylose, on the other hand, is less strongly branched and also has a low molecular weight (11). Amylopectin can contribute to an increase of the resistant starch fraction in a carbohydrate. This happens due to the retrogradation of amylopectin in the course of which resistant starch is formed. During retrogradation, the molecules in the gel network become increasingly entangled. The branching process of amylopectin over time also contributes to the content of resistant starch, as the resulting low-molecular polymers promote retrogradation (12).
 

Pectin belongs to the family of heteropolysaccharides and as such is mainly found in the primary cell walls of plants and in the skins of various fruits and vegetables. The peel of oranges, for example, contains up to 30 % pectin and that of apples about 15 %, therefore citrus peel and apple pomace are often used as sources for natural pectin. Dietary fiber is a popular functional food component and enjoys a broad pharmacological application. Pectin is soluble in hot water and forms gels when cooled. This effect is used in the food industry, where pectin is used as a gelling agent during the production of jams and fruit jellies. The cholesterol-reducing effect of pectin is also based on its solubility. Dietary fiber binds cholesterol and bile acids in the intestines and thus promotes their excretion (7). Pectin has further positive effects on the organism, especially on the gastrointestinal tract. These include, for example, immune modulation as well as anticarcinogenic and ulcus preventive properties. In addition, pectin can selectively stimulate positive intestinal bacteria (13). Pectin has a bifidogenic effect and stimulates the growth of health-promoting microorganisms. For example, it influences the bacterial adhesion of Lactobacillus rhamnosus. A study by Nazzaro et al. (2012) investigated, among other things, the influence of pectin on the developmental ability of L. acidophilus in a simulated gastric and pancreatic passage. In comparison to control (glucose), pectin induced a kind of cellular stress resistance to gastrointestinal juices. Furthermore, contrary to control, pectin led to the formation of the biomolecule butyrate (6).
 

The demand for new candidates that can independently and selectively stimulate the growth of positive bacterial strains, for example lactic acid bacteria, is high. The aim is to prevent fermentation by other, possibly pathogenic organisms as far as possible. Starch products, such as, resistant starch, or dextrin, are a promising source. Resistant dextrins form a new group of soluble dietary fibers. The short-chain carbohydrate polymers are usually obtained from potato or corn starch by heat and/or acid treatment and are almost completely resistant to human digestion. The production method influences the proportion of the resistant fraction, i.e. the percentage that reaches the colon and interacts with the microbiota there. Dextrin serves the intestinal flora as a useful source of carbon. Studies have shown that dextrins are particularly useful as a food source for beneficial bacterial strains. Experiments with resistant dextrin demonstrated an increase in carbohydrase flora, i.e. the bacteria that form the enzymes of carbohydrate degradation, and a decrease in the potentially dangerous Clostridium perfringens in the colon. Similar formulations in animal experiments led to an increased production of short-chain fatty acids in the colon (14) (15).

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