- Email: [email protected]
PROBIOTICS
4792 PROBIOTICS preterm human milk. American Journal of Clinical Nutrition 52(2): 254–262. Lucas A, Stafford M, Morley R et al. (1999) Efficacy and safety of long-chain polyunsaturated fatty acid supplementation of infant-formula milk: a randomised trial [see comments]. Lancet 354(9194): 1948–1954. Lundstrom U, Siimes MA and Dallman PR (1977) At what age does iron supplementation become necessary in lowbirth-weight infants? Journal of Pediatrics 91(6): 878– 883. Putet G (1993) Energy. In: Tsang RC, Lucas A, Uauy R and Zlotkin S (eds) Nutritional Needs of the Preterm Infant. Scientific Basis and Practical Guidelines, pp. 15–28.Cincinnati, OH: Digital Educational Publishing. Reifen RM and Zlotkin S (1993) Microminerals. In: Tsang RC, Lucas A, Uauy R and Zlotkin S (eds) Nutritional Needs of the Preterm Infant. Scientific Basis and Prac-
tical Guidelines, pp. 195–207. Cincinnati, OH: Digital Educational Publishing. Schulze KF, Stefanski M, Masterson J et al. (1987) Energy expenditure, energy balance, and composition of weight gain in low birth weight infants fed diets of different protein and energy content. Journal of Pediatrics 110(5): 753–759. Tyson JE, Wright LL, Oh W et al. (1999) Vitamin A supplementation for extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network [see comments]. New England Journal of Medicine 340(25): 1962–1968. Vileisis RA (1987) Effect of phosphorus intake in total parenteral nutrition infusates in premature neonates. Journal of Pediatrics 110(4): 586–590.
PROBIOTICS S E Gilliland, Oklahoma State University, Stillwater, OK, USA Copyright 2003, Elsevier Science Ltd. All Rights Reserved.
Background 0001
tbl0001
Probiotics may be defined as selected viable microorganisms that, following consumption in a food or feed, have potential for improving health or nutrition of man or animal. Bacteria in this group may be used to ferment food or are added to food as dietary supplements. Foods for human consumption containing these organisms are sometimes referred to as functional foods. A number of different bacterial species have been suggested as probiotics (Table 1). The major species that have been considered over the years, however, are Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium species, and Bifidobacterium longum.
Table 1 Bacteria used as probiotics Major bacteria Lactobacillus acidophilus Lactobacillus casei Bifidobacterium longum Bifidobacterium bifidum Others Lactobacillus ruterii Lactobacillus johnsonii Bifidobacterium lactis Lactobacillus plantarum
Dairy products provide an excellent carrier for these probiotic bacteria especially Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium species. Most of these can readily utilize lactose as an energy source for growth; thus, an important requirement for their growth in the intestinal tract is provided by the milk. Additionally, many of them have been used for centuries in the manufacture of cultured dairy products and thus are generally regarded as safe. This means that there should be no objection to their being used as dietary adjuncts in milk products. In the early 1900s, Eli Metchnikoff advocated that man should consume, on a daily basis, milk fermented by Lactobacillus species to displace microorganisms in the intestinal tract that produce toxic substances that could shorten man’s life. Thus, he felt that consumption of such fermented milk would prolong life. This theory was the beginning of what we refer to today as foods containing probiotic bacteria. Several dairy products containing probiotic bacteria are marketed today, and the most widely encountered product is yogurt. It is not uncommon to read on the label of a yogurt product that it was made with a culture including Lactobacillus acidophilus and/or Bifidobacterium species. These are not the bacteria that have traditionally been used to manufacture yogurt. The traditional yogurt starter cultures are Streptococcus salivarius ssp. thermophilus and Lactobacillus delbrueckii ssp. bulgaricus. Neither of these two organisms is traditionally listed as a probiotic, because they are not expected to survive and grow in the intestinal tract, whereas
0002
0003
PROBIOTICS
probiotics do. In the USA, nonfermented milk products are available that contain added cells of Lactobacillus acidophilus and/or bifidobacteria. Following supplementation of the pasteurized milk with these two organisms, it is stored under refrigeration so that the probiotic bacteria do not grow in the milk. In this case, milk serves as a carrier for the organisms, and the product, of course, does not have the sour or tart taste normally associated with fermented dairy products. This provides a product containing the probiotics for those people who do not desire the taste and flavor associated with fermented products.
Potential Benefits 0004
tbl0002
When Eli Metchnikoff proposed his theory to prolong life, the primary benefit he proposed from the consumption of the fermented milk product was to control the intestinal microflora. Since the interest in probiotics was renewed some 20–30 years ago, several other potential benefits have come to light (Table 2). While these potential health and nutritional benefits appear to be very important to mankind, most of them have not been thoroughly proven. In order to firmly establish whether or not the benefits can actually be produced, relatively large clinical trials will be required, especially in the case of humans. A large number of factors must be considered when undertaking such a monumental task. A very important aspect is the selection of the probiotic bacteria to be utilized. This will be discussed in a later section of this chapter. Most of the possible benefits listed in Table 2 have to do with human health and nutrition. However, with the pending ban on the use of subtherapeutic levels of antibiotics in livestock feed, there is tremendous interest in the role of probiotics as supplements for animal feed. The primary interest here focuses on controlling intestinal pathogens as well as improving nutrient utilization. The subtherapeutic antibiotics, which have been used for years as livestock feed supplements, have been shown in many cases to improve the growth and performance of livestock. While this may be due in part to control of undesirable microorganisms in the
Table 2 Potential health and/or nutritional benefits from probiotics in the diet . . . . . .
Control of intestinal pathogens Modulation of the immune system Control lactose maldigestion Hypocholesterolemic action Control of colon cancer Improved utilization of nutrients
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digestive tract, other mechanisms are also likely. Probiotic bacteria offer very good opportunities for use as livestock feed supplements to achieve these goals.
Control of Intestinal Infections In the literature, there are many studies on the use of Lactobacillus species to control intestinal infections. Unfortunately, many of these earlier studies were not well designed. In most cases, the probiotics, primarily Lactobacillus species, were used as a therapeutic rather than a preventative agent. In many cases, proper controls were not included in the studies, so valid observations as to the effectiveness of the probiotic could not be made. Additionally, in many of these studies, there was very little information concerning the particular culture of probiotic involved, especially with regard to origin or characteristics giving it the potential for producing the desired effect. While it is possible that they may function in a therapeutic manner, it is more reasonable to consider probiotics as a prophylactic treatment for intestinal infections. This has been shown in a well-designed study involving germ-free chickens. In this study, germ-free chickens were fed a culture of Lactobacillus acidophilus and 2 days later were challenged with either Salmonella typhimurium or Staphylococcus aureus. In the same study, another series of germfree chickens were fed the pathogenic organisms initially and then fed Lactobacillus acidophilus (as a therapeutic treatment). In the therapeutic experiments, the Lactobacillus acidophilus had minimal effect, but those animals fed the Lactobacillus acidophilus initially (prior to challenge with the pathogen) survived much better than did those animals that were challenged with the pathogen first. These results suggest that it is important to have the Lactobacillus acidophilus initially (i.e., as a prophylactic treatment) to ward off intestinal pathogens. The scientists conducting this study also indicated that it was desirable to provide the probiotic organism on a continuing basis in a diet for best control of the pathogens. Other studies involving animal models have confirmed these types of results. It is difficult to perform such studies in humans, since it is very difficult, if not impossible, in a university setting to obtain approval for doing challenge studies with intestinal pathogens using human test subjects. However, there have been some well-designed studies in which feeding products containing selected probiotic bacteria have been shown to be effective in helping control naturally occurring intestinal disorders brought on by intestinal pathogens, especially in young children. Based on what is known about the variation among strains and species of this group of bacteria, it is
0005
0006
4794 PROBIOTICS tbl0003
Table 3 Suggested mechanisms through which probiotics might control intestinal infections . . . .
0007
Production of antimicrobial substances Competition for nutrients (not likely) Competitive exclusion Stimulation or modulation of the body’s immune system
very important to properly select a strain or culture for use as a probiotic to control intestinal infections. Several mechanisms have been suggested to be responsible for the control of intestinal pathogens by probiotic bacteria (Table 3). Probiotic bacteria can produce several types of antimicrobial agents, including acid, bacteriocins, and hydrogen peroxide. However, because of the proteolytic enzymes in the intestine, the role of bacteriocins (most of which are easily inactivated by proteolysis) may be very limited. Because of the low levels of oxygen, peroxide formation should be minimal. Acid (especially acetic acid) is likely the most involved of these antimicrobial agents. Some have suggested competition for nutrients as a mechanism, although this is unlikely. Competitive exclusion, where probiotic bacteria occupy the binding sights on the intestinal wall, thus preventing attachment of pathogenic organisms, may be a main factor in some cases. Stimulation or modulation of the body’s immune system, which is discussed in the next section, appears to be a very likely mechanism.
Modulation of the Immune System 0008
Stimulation or modulation of the body’s immune system by probiotic bacteria can have health benefits. Probiotic bacteria can cause the body to secrete antimicrobial substances into the intestines. These antimicrobial substances then in turn inhibit the growth of undesirable microorganisms. This is a very interesting and challenging area of research and is currently receiving considerable attention throughout the world. While most of the research on modulation of the immune system has involved animal studies, several studies have focused on the influence of feeding cells of Lactobacillus acidophilus on the immune system of humans. In these studies, an increase in the secretion of substances, which are considered inhibitory for certain intestinal pathogens, into the intestine was observed. The ability to modulate the body’s immune system through the consumption of probiotic bacteria provides a great opportunity to control intestinal pathogens as well as potentially to have other benefits for the consumer.
Lactose Maldigestion A number of terms, including ‘lactose malabsorption‘ and ‘lactose intolerance,‘ have been used to describe the inability of a person to digest lactose adequately. ‘Lactose maldigestion‘ seems to be a more accurate term to describe this condition in humans, since it refers to the inability of a person to digest lactose adequately. This is primarily due to the absence of sufficient amounts of the enzyme b-galactosidase in the small intestine. Microorganisms in the intestinal tract can influence the ability to digest lactose. For instance, dietary lactose is highly toxic to germ-free chicks, whereas chicks with a normal intestinal flora, are able to digest the lactose. This difference has been attributed to the lactose-hydrolyzing enzymes provided by the microorganisms in the intestinal tract of conventional chicks. Some cultured or culture-containing milk products have been shown to be beneficial. For instance, the consumption of milk containing cells of Lactobacillus acidophilus has been shown to improve the utilization of lactose by lactose maldigestors. A similar phenomenon can be observed by the consumption of cultured yogurt containing viable starter bacteria. The primary requirement for these probiotic and yogurt bacteria to provide this benefit is that they contain adequate levels of the enzyme b-galactosidase (Figure 1). The traditional bacteria used to manufacture yogurt, Lactobacillus delbrueckii ssp. bulgaricus and Streptococcus salivarius ssp. thermophilus, are not expected to survive and grow in the intestinal tract, because they lack bile tolerance. However, when they interact with bile in the intestinal tract, their permeability is altered, permitting lactose to enter the cells to be hydrolyzed. This results in the organisms being able to hydrolyze lactose at a more rapid rate than they would in milk in the absence of bile. Thus, without growing in the intestinal tract, these two species of bacteria can provide a benefit for those people unable to digest lactose adequately. Research has shown that, while the permeability of these cells was altered in the presence of bile, it was not sufficient to completely rupture the cells. The b-galactosidase remains in the cell having the increased permeability. Bile has a similar effect on Lactobacillus acidophilus in that the permeability of the cells increases
LACTOSE
β-galactosidase
0009
0010
0011
0012
GLUCOSE + GALACTOSE
Figure 1 Action required by probiotics to provide benefit for lactose maldigestion.
fig0001
PROBIOTICS
in the presence of bile enabling lactose to enter more freely and be hydrolyzed. Thus, the mechanism whereby cells of Lactobacillus acidophilus can alleviate the problems of lactose maldigestion is similar to that of yogurt. However, Lactobacillus acidophilus has the added advantage that it can grow in the presence of the bile, and so new cells can be produced during its growth in the intestine, providing even more of the enzyme necessary for hydrolyzing lactose. When preparing a product to which cells Lactobacillus acidophilus are added, it is important that the cells have been grown in a medium containing lactose as a sugar source to insure that cells contain adequate levels of the enzyme b-galactosidase. If not, the amount of enzyme probably will be too low to produce the desired benefit with regard to lactose maldigestion as rapidly as desired.
Hypocholesterolemic Actions 0013
0014
The risk of coronary heart disease in hypercholesterolemic persons can be significantly reduced by lowering serum cholesterol levels. Germ-free animals on an elevated cholesterol diet accumulate approximately twice as much cholesterol in the blood as conventional animals on a similar diet. This suggests the possibility that microorganisms in the intestinal tract can influence serum cholesterol levels. Consumption of organisms such as Lactobacillus acidophilus can aid in the control of serum cholesterol levels in humans. Two studies published in the 1970s showed this to occur. In one of the studies, infants fed a formula supplemented with Lactobacillus acidophilus exhibited reduced serum cholesterol levels associated with increased numbers of lactobacilli in the feces, compared with infants receiving the control formula. This suggests that the lactobacilli may be associated with the reduction of serum cholesterol levels. In another study, a group of men fed milk fermented by the natural flora in raw milk exhibited unexpected reduced serum cholesterol levels. The fermentation apparently included what was described as a culture of Lactobacillus, although the organism was not identified. Because of these studies, considerable research has focused on the potential for Lactobacillus acidophilus or related bacteria to exert beneficial influences on serum cholesterol levels. Lactobacillus acidophilus growing in a laboratory medium supplemented with cholesterol and bile salts under anaerobic conditions will assimilate cholesterol. This ability to assimilate cholesterol varies tremendously among strains of this species of bacteria. Results from a feeding trial using pigs on a high-cholesterol diet as an animal model revealed that supplementation of the diet with a strain
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of Lactobacillus acidophilus that assimilated cholesterol during growth in a laboratory medium had a significant beneficial effect on serum cholesterol, whereas a strain that did not assimilate cholesterol during growth in a laboratory medium did not. This suggests the importance of screening cultures for use as a probiotic to produce a beneficial effect on serum cholesterol levels. In another feeding trial involving pigs with diet-induced hypercholesterolemia, animals receiving cells of Lactobacillus acidophilus exhibited a significant positive correlation between the reduction of serum cholesterol levels and the concentration of cholic acid in the serum. The decline in serum cholesterol was initiated more rapidly and reached a significantly lower level in the animals fed the lactobacilli than in those not fed the lactobacilli. Such data suggest the possibility that the lactobacilli interfered with the enterohepatic circulation of bile acids, which can be an important factor in reducing serum cholesterol levels. This also suggests another activity of the lactobacilli, which may be important in controlling serum cholesterol levels. Lactobacillus acidophilus has the ability to deconjugate bile acids through the action of bile salt hydrolase. Free bile acids being less well absorbed from the small intestine than conjugated acids are more likely to be excreted from the body. Replacement of these excreted bile acids involves the synthesis of new bile acids from cholesterol in the body. This has a tendency to lower the cholesterol pool in the body. This represents the major pathway for removing cholesterol from the human body. An additional advantage for the deconjugation is that free bile acids do not support the absorption of cholesterol for the intestinal tract as well as conjugated acids. The mechanism whereby consumption of fermented milk products containing cells of Lactobacillus acidophilus or other probiotics may reduce levels of serum cholesterol appears to include their ability to assimilate cholesterol and/or deconjugate bile acids (Table 4). Some of the cholesterol assimilated by Lactobacillus acidophilus is incorporated in the cellular membranes of the organisms. Bifidobacterium longum also can incorporate some cholesterol into its membrane, but Lactobacillus casei does not. All three species have the ability to deconjugate bile salts.
Table 4 Activities of probiotic cultures important for imparting a hypocholesterolemic effect . Assimilation of cholesterol . Deconjugation of bile salts
0015
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4796 PROBIOTICS
Control of Colon Cancer 0016
0017
Some lactic acid bacteria can produce anticarcinogenic or antimutagenic compounds, which can result in the inhibition of some types of tumor cells in animals. For example, rats that had been implanted with ascites tumor cells and fed milk fermented with Lactobacillus acidophilus exhibited a lower proliferation of tumor cells than those in the control group. The conclusion was that the Lactobacillus species produced substances during growth in the intestine that was antagonistic toward the proliferation of these tumor cells. Other studies have shown that certain fermented milks have a beneficial influence on the proliferation of colon tumor cells in rats. Feeding rats cells of Lactobacillus reduced the activity of three enzymes capable of converting procarcinogens into carcinogens in the intestinal tract. Similar results have been shown in human studies. These enzymes were bglucuronidase, azoreductase, and nitroreductase. Reduction of the level of activity of these enzymes in the intestinal tract can reduce the chances of carcinogens being formed. The enzymes apparently are of microbial origin. Thus, the potential anticarcinogenic activity of feeding Lactobacillus acidophilus may, in this case, be related to the control of undesirable microorganisms in the intestinal tract. In other studies, the consumption of milk containing cells of Lactobacillus casei activated macrophages in mice. This observation was based on increases in enzyme activity associated with macrophages. This suggests another potential means, whereby the consumption of a selected probiotic culture may influence proliferation of tumor cells in the body.
Other Benefits 0018
One of the main interests in the livestock industry in using probiotic bacteria as feed supplements is to improve nutrient utilization resulting in improved growth and/or feed efficiency of the livestock. While there is great interest in this area, there is very little evidence reported in the scientific literature to indicate how such benefits might occur. It is possible that such benefits can result from the action of certain enzymes associated with the probiotic bacteria. This could be similar, for instance, to the beneficial effect of yogurt bacteria and Lactobacillus acidophilus on lactose maldigestion in humans that results from b-galactosidase associated with the bacterial cells. Selection of a culture of Lactobacillus acidophilus with a high level of amylase activity for inclusion as a probiotic in the diet of young pigs can improve starch utilization in the young animal. In a feeding
trial involving the use of such a culture, improved growth and feed efficiency of weaning aged pigs were observed as a result of including the selected culture in the diet. The benefit was attributed to the amylase activity of the culture. It is possible that other enzymes that could improve the digestion of other nutrients may be present in some bacteria used as probiotics that could result in improved growth and feed efficiency of the livestock. Of course, the improved growth may relate to the control of undesirable microorganisms in the animal’s intestinal tract. There is also interest in the livestock and pet-food industries in using probiotics to help control intestinal infections in animals.
Selection of Probiotic Culture While there are a number of potential benefits from the inclusion of a probiotic culture in the diet, it is essential that a culture be properly selected for such use. One culture, that is one strain of one species, should not be expected to provide all of the potential benefits that might be derived from probiotics. To help insure that the culture is successful and has a positive effect, certain requirements are to be met (Table 5). Since, in most cases, the sight of action of the probiotic organisms is the intestinal tract, it is generally accepted that the organism should be a normal inhabitant of the intestinal tract. There is strong evidence in the literature indicating that many of these probiotic bacteria exhibit host specificity; for example, a strain of Lactobacillus acidophilus originating in the intestinal tract of a calf should not be expected to function equally well in the intestinal tract of a pig or of a human. Thus, it is desirable to use a selected strain of bacteria that originated in the host species for which the product is to be used. If it is to be used as a probiotic for humans, it is highly desirable that the probiotic organism originated in the human intestines. In order to avoid problems with regulatory agencies, it is desirable that the organism of choice has a history of having been used for producing fermented food products.
Table 5 Important factors to consider in selection of a probiotic culture . . . . . . .
Normal inhabitant of intestine Host specificity Acid tolerance Bile tolerance Stability during production and delivery Production of desired health/nutritional benefit One strain would be unlikely to provide all possible benefits
0019
tbl0005
PROBIOTICS
0020
The organism should be resistant to gastric acidity to survive passage through the stomach. The main organisms considered for use as probiotics (i.e., lactobacilli) are acid-tolerant. However, resistance to acidity varies among strains and species, so it must be considered. If the organism is expected to grow and function in the intestinal tract, it must have a certain degree of bile tolerance. The bile resistance based on the ability of the organism to grow in the presence of bile acids varies tremendously among strains of each species of probiotic bacteria. The minimum level of bile tolerance required is not known, but it is suggested that the most bile-resistant strain that will provide the desired benefit be selected. The probiotic culture must be stable during production and storage of the food or feed containing it. This is often the most challenging factor in providing a probiotic organism that has adequate levels of viability at the time of consumption. The most important characteristic of course is that the probiotic culture produce the desired effect. Therefore, it is desirable that some sort of laboratory screening test for the desired effect be implemented. This is not always easy. However, if the organism for instance is to be used for improving lactose utilization, it would be desirable to select one having a high level of b-galactosidase activity. If it is to be used for controlling serum cholesterol levels, it is desirable that the organism not only assimilate cholesterol but also have a high degree of ability to deconjugate bile acids. In order to develop useful screening tests, it is of course essential that we understand how the probiotic organism functions to provide the desirable benefit. In many cases, we simply do not know the answer to this mechanism at this point. A major factor in selection of a specific organism for use as a probiotic is to remember that one strain should not be expected to provide all potential benefits. Far more is required in the selection process than to select a culture just because it is Lactobacillus acidophilus, for example. There is a great variation among strains of this bacterial species. Such variation also occurs among strains of other species of probiotic bacteria.
Dietary Delivery of the Probiotic 0021
If the probiotic organism is expected to provide its benefit during growth and action in the intestinal tract, it is reasonable to assume that the organism must be viable at the time of consumption. It is also desirable and recommended that the probiotic be consumed on a continuing basis. The numbers of viable probiotic bacteria required in a food or feed product to provide the benefit are not known. The
4797
actual numbers required probably will vary with the organism and the expected function. Some have suggested, particularly with regard to milk products, that the probiotic should be present at a level of one to two million per milliliter; however, these numbers are not based on scientific data but are based more on an economic situation reflecting the cost of the organism. Research is needed to answer the question with regard to the optimum numbers required. It is essential that the organism be stable and that the desired characteristics be maintained during the production of the probiotic culture, during its storage, and delivery in the food or feed. This is often the greatest challenge in the use of probiotic bacteria. The stability of the organism during storage and delivery can be greatly influenced by the conditions under which the bacteria are grown. For instance, the growth of Lactobacillus acidophilus at pH 5 has resulted in cultures that are more stable during storage when added to refrigerated milk than the same cultures grown at a higher pH. The storage stability, especially during frozen and refrigerated storage, varies among strains of a given bacterial species used as a probiotic. Thus, this becomes a factor to consider in selecting the organism for use as a probiotic. The use of probiotic bacteria such as Lactobacillus acidophilus in conjunction with yogurt can be accomplished by either including the probiotic as part of the starter culture or adding cells of the probiotic bacteria after the product has been manufactured. Of course, it would be desirable to use the probiotic as part of the inoculum (i.e., starter culture) used in the manufacture of yogurt in order to yield higher numbers of the probiotic bacteria during the incubation period for the fermentation. However, most of the probiotic bacteria do not grow well under such conditions, and very little increase in numbers is achieved during the incubation process involved in the manufacture of yogurt. Research is needed to provide means of increasing the numbers of probiotic bacteria that grow during the manufacture of a product such as yogurt when the organism is used as a part of the inoculum for manufacturing the fermented milk. In summary, once a desired probiotic culture has been selected, it is important to develop procedures for producing the culture, storing the culture, and delivering the culture in the food or feed without damaging the desired characteristics. See also: Bifidobacteria in Foods; Cholesterol: Properties and Determination; Role of Cholesterol in Heart Disease; Colon: Cancer of the Colon; Immunology of Food; Lactic Acid Bacteria; Lactose; Salmonella: Salmonellosis; Staphylococcus: Food Poisoning
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4798 PROSTAGLANDINS AND LEUKOTRIENES
Further Reading Bezkorovainy A and Catchpole RM (1989) Biochemistry and Physiology of Bifidobacteria. Boca Raton, FL: CRC Press. Fuller R (ed.) (1992) Probiotics the Scientific Basis. New York: Chapman & Hall. Gilliland SE (1990) Health and nutritional benefits from lactic acid bacteria. FEMS Microbiology Reviews 87: 175–188. Klein G, Pack A, Bonaparte C and Renter G (1998) Taxonomy and physiology of probiotic lactic acid bacteria. International Journal of Food Microbiology 41: 103–125.
Ouwehand AC, Kirjavainen PV, Shortt C and Salminen S (1999) Probiotics: mechanisms and established effects. International Dairy Journal 9: 43–52. Robinson RK (ed.) (1991) Therapeutic Properties of Fermented Milks. Barking, UK: Elsevier Science. Sissons JW (1989) Potential of probiotic organisms to prevent diarrhoea and promote digestion in farm animals – a review. Journal of the Science of Food and Agriculture 49: 1–13. Tamine AY and Robinson RK (1999) Yoghurt Science and Technology, 2nd edn. Boca Raton, FL: CRC Press.
Process Control See Plant Design: Basic Principles; Designing for Hygienic Operation; Process Control and Automation; Instrumentation and Process Control
Processed Cheese See Cheeses: Types of Cheese; Starter Cultures Employed in Cheese-making; Chemistry and Microbiology of Maturation; Manufacture of Extra-hard Cheeses; Manufacture of Hard and Semihard Varieties of Cheese; Cheeses with ‘Eyes‘; Soft and Special Varieties; White Brined Varieties; Quarg and Fromage Frais; Processed Cheese; Dietary Importance; Mold-ripened Cheeses: Stilton and Related Varieties; Surface Mold-ripened Cheese Varieties; Risk Assessment
PROSTAGLANDINS AND LEUKOTRIENES S Katayama, Saitama Medical School, Iruma-gun, Saitama, Japan J B Lee, State University of New York, New York, USA Copyright 2003, Elsevier Science Ltd. All Rights Reserved.
Background 0001
Prostaglandins (PGs) were discovered in the 1930s and were first chemically isolated and identified in sheep seminal vesicles and renal medulla in the 1960s. Although together with thromboxanes (TXs) and leukotrienes (LTs), the PGs possess the most potent and most divergent biological activities of any naturally occurring compounds, their true physiological role in many instances remains unknown. From a pathophysiological viewpont, an absolute or relative deficiency of PGs relative to TXs has been implicated in the etiology of hypertension, thrombosis, and
atherogenesis for many years. Since PGs and TXs are derived from essential fatty acids, the role of dietary intake of these fatty acids in PG and TX production, particularly in relation to cardiovascular system, will be examined. The possible role of dietary essential fatty acids on LT and PG production in relation to inflammation, the immune system, and gastric function will also be discussed.
Chemistry In the 1930s, it was reported that fresh human semen causes rhythmic contractions of human endometrium. The active substance was called ‘prostaglandin.‘ In the 1960s, PG was determined to be a mixture of biologically active compounds, which were isolated from sheep seminal vesicles and identified as PGE1–3 and PGF1–2. These compounds were independently isolated from extracts of rabbit kidney
0002
tical Guidelines, pp. 195–207. Cincinnati, OH: Digital Educational Publishing. Schulze KF, Stefanski M, Masterson J et al. (1987) Energy expenditure, energy balance, and composition of weight gain in low birth weight infants fed diets of different protein and energy content. Journal of Pediatrics 110(5): 753–759. Tyson JE, Wright LL, Oh W et al. (1999) Vitamin A supplementation for extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network [see comments]. New England Journal of Medicine 340(25): 1962–1968. Vileisis RA (1987) Effect of phosphorus intake in total parenteral nutrition infusates in premature neonates. Journal of Pediatrics 110(4): 586–590.
PROBIOTICS S E Gilliland, Oklahoma State University, Stillwater, OK, USA Copyright 2003, Elsevier Science Ltd. All Rights Reserved.
Background 0001
tbl0001
Probiotics may be defined as selected viable microorganisms that, following consumption in a food or feed, have potential for improving health or nutrition of man or animal. Bacteria in this group may be used to ferment food or are added to food as dietary supplements. Foods for human consumption containing these organisms are sometimes referred to as functional foods. A number of different bacterial species have been suggested as probiotics (Table 1). The major species that have been considered over the years, however, are Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium species, and Bifidobacterium longum.
Table 1 Bacteria used as probiotics Major bacteria Lactobacillus acidophilus Lactobacillus casei Bifidobacterium longum Bifidobacterium bifidum Others Lactobacillus ruterii Lactobacillus johnsonii Bifidobacterium lactis Lactobacillus plantarum
Dairy products provide an excellent carrier for these probiotic bacteria especially Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium species. Most of these can readily utilize lactose as an energy source for growth; thus, an important requirement for their growth in the intestinal tract is provided by the milk. Additionally, many of them have been used for centuries in the manufacture of cultured dairy products and thus are generally regarded as safe. This means that there should be no objection to their being used as dietary adjuncts in milk products. In the early 1900s, Eli Metchnikoff advocated that man should consume, on a daily basis, milk fermented by Lactobacillus species to displace microorganisms in the intestinal tract that produce toxic substances that could shorten man’s life. Thus, he felt that consumption of such fermented milk would prolong life. This theory was the beginning of what we refer to today as foods containing probiotic bacteria. Several dairy products containing probiotic bacteria are marketed today, and the most widely encountered product is yogurt. It is not uncommon to read on the label of a yogurt product that it was made with a culture including Lactobacillus acidophilus and/or Bifidobacterium species. These are not the bacteria that have traditionally been used to manufacture yogurt. The traditional yogurt starter cultures are Streptococcus salivarius ssp. thermophilus and Lactobacillus delbrueckii ssp. bulgaricus. Neither of these two organisms is traditionally listed as a probiotic, because they are not expected to survive and grow in the intestinal tract, whereas
0002
0003
PROBIOTICS
probiotics do. In the USA, nonfermented milk products are available that contain added cells of Lactobacillus acidophilus and/or bifidobacteria. Following supplementation of the pasteurized milk with these two organisms, it is stored under refrigeration so that the probiotic bacteria do not grow in the milk. In this case, milk serves as a carrier for the organisms, and the product, of course, does not have the sour or tart taste normally associated with fermented dairy products. This provides a product containing the probiotics for those people who do not desire the taste and flavor associated with fermented products.
Potential Benefits 0004
tbl0002
When Eli Metchnikoff proposed his theory to prolong life, the primary benefit he proposed from the consumption of the fermented milk product was to control the intestinal microflora. Since the interest in probiotics was renewed some 20–30 years ago, several other potential benefits have come to light (Table 2). While these potential health and nutritional benefits appear to be very important to mankind, most of them have not been thoroughly proven. In order to firmly establish whether or not the benefits can actually be produced, relatively large clinical trials will be required, especially in the case of humans. A large number of factors must be considered when undertaking such a monumental task. A very important aspect is the selection of the probiotic bacteria to be utilized. This will be discussed in a later section of this chapter. Most of the possible benefits listed in Table 2 have to do with human health and nutrition. However, with the pending ban on the use of subtherapeutic levels of antibiotics in livestock feed, there is tremendous interest in the role of probiotics as supplements for animal feed. The primary interest here focuses on controlling intestinal pathogens as well as improving nutrient utilization. The subtherapeutic antibiotics, which have been used for years as livestock feed supplements, have been shown in many cases to improve the growth and performance of livestock. While this may be due in part to control of undesirable microorganisms in the
Table 2 Potential health and/or nutritional benefits from probiotics in the diet . . . . . .
Control of intestinal pathogens Modulation of the immune system Control lactose maldigestion Hypocholesterolemic action Control of colon cancer Improved utilization of nutrients
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digestive tract, other mechanisms are also likely. Probiotic bacteria offer very good opportunities for use as livestock feed supplements to achieve these goals.
Control of Intestinal Infections In the literature, there are many studies on the use of Lactobacillus species to control intestinal infections. Unfortunately, many of these earlier studies were not well designed. In most cases, the probiotics, primarily Lactobacillus species, were used as a therapeutic rather than a preventative agent. In many cases, proper controls were not included in the studies, so valid observations as to the effectiveness of the probiotic could not be made. Additionally, in many of these studies, there was very little information concerning the particular culture of probiotic involved, especially with regard to origin or characteristics giving it the potential for producing the desired effect. While it is possible that they may function in a therapeutic manner, it is more reasonable to consider probiotics as a prophylactic treatment for intestinal infections. This has been shown in a well-designed study involving germ-free chickens. In this study, germ-free chickens were fed a culture of Lactobacillus acidophilus and 2 days later were challenged with either Salmonella typhimurium or Staphylococcus aureus. In the same study, another series of germfree chickens were fed the pathogenic organisms initially and then fed Lactobacillus acidophilus (as a therapeutic treatment). In the therapeutic experiments, the Lactobacillus acidophilus had minimal effect, but those animals fed the Lactobacillus acidophilus initially (prior to challenge with the pathogen) survived much better than did those animals that were challenged with the pathogen first. These results suggest that it is important to have the Lactobacillus acidophilus initially (i.e., as a prophylactic treatment) to ward off intestinal pathogens. The scientists conducting this study also indicated that it was desirable to provide the probiotic organism on a continuing basis in a diet for best control of the pathogens. Other studies involving animal models have confirmed these types of results. It is difficult to perform such studies in humans, since it is very difficult, if not impossible, in a university setting to obtain approval for doing challenge studies with intestinal pathogens using human test subjects. However, there have been some well-designed studies in which feeding products containing selected probiotic bacteria have been shown to be effective in helping control naturally occurring intestinal disorders brought on by intestinal pathogens, especially in young children. Based on what is known about the variation among strains and species of this group of bacteria, it is
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Table 3 Suggested mechanisms through which probiotics might control intestinal infections . . . .
0007
Production of antimicrobial substances Competition for nutrients (not likely) Competitive exclusion Stimulation or modulation of the body’s immune system
very important to properly select a strain or culture for use as a probiotic to control intestinal infections. Several mechanisms have been suggested to be responsible for the control of intestinal pathogens by probiotic bacteria (Table 3). Probiotic bacteria can produce several types of antimicrobial agents, including acid, bacteriocins, and hydrogen peroxide. However, because of the proteolytic enzymes in the intestine, the role of bacteriocins (most of which are easily inactivated by proteolysis) may be very limited. Because of the low levels of oxygen, peroxide formation should be minimal. Acid (especially acetic acid) is likely the most involved of these antimicrobial agents. Some have suggested competition for nutrients as a mechanism, although this is unlikely. Competitive exclusion, where probiotic bacteria occupy the binding sights on the intestinal wall, thus preventing attachment of pathogenic organisms, may be a main factor in some cases. Stimulation or modulation of the body’s immune system, which is discussed in the next section, appears to be a very likely mechanism.
Modulation of the Immune System 0008
Stimulation or modulation of the body’s immune system by probiotic bacteria can have health benefits. Probiotic bacteria can cause the body to secrete antimicrobial substances into the intestines. These antimicrobial substances then in turn inhibit the growth of undesirable microorganisms. This is a very interesting and challenging area of research and is currently receiving considerable attention throughout the world. While most of the research on modulation of the immune system has involved animal studies, several studies have focused on the influence of feeding cells of Lactobacillus acidophilus on the immune system of humans. In these studies, an increase in the secretion of substances, which are considered inhibitory for certain intestinal pathogens, into the intestine was observed. The ability to modulate the body’s immune system through the consumption of probiotic bacteria provides a great opportunity to control intestinal pathogens as well as potentially to have other benefits for the consumer.
Lactose Maldigestion A number of terms, including ‘lactose malabsorption‘ and ‘lactose intolerance,‘ have been used to describe the inability of a person to digest lactose adequately. ‘Lactose maldigestion‘ seems to be a more accurate term to describe this condition in humans, since it refers to the inability of a person to digest lactose adequately. This is primarily due to the absence of sufficient amounts of the enzyme b-galactosidase in the small intestine. Microorganisms in the intestinal tract can influence the ability to digest lactose. For instance, dietary lactose is highly toxic to germ-free chicks, whereas chicks with a normal intestinal flora, are able to digest the lactose. This difference has been attributed to the lactose-hydrolyzing enzymes provided by the microorganisms in the intestinal tract of conventional chicks. Some cultured or culture-containing milk products have been shown to be beneficial. For instance, the consumption of milk containing cells of Lactobacillus acidophilus has been shown to improve the utilization of lactose by lactose maldigestors. A similar phenomenon can be observed by the consumption of cultured yogurt containing viable starter bacteria. The primary requirement for these probiotic and yogurt bacteria to provide this benefit is that they contain adequate levels of the enzyme b-galactosidase (Figure 1). The traditional bacteria used to manufacture yogurt, Lactobacillus delbrueckii ssp. bulgaricus and Streptococcus salivarius ssp. thermophilus, are not expected to survive and grow in the intestinal tract, because they lack bile tolerance. However, when they interact with bile in the intestinal tract, their permeability is altered, permitting lactose to enter the cells to be hydrolyzed. This results in the organisms being able to hydrolyze lactose at a more rapid rate than they would in milk in the absence of bile. Thus, without growing in the intestinal tract, these two species of bacteria can provide a benefit for those people unable to digest lactose adequately. Research has shown that, while the permeability of these cells was altered in the presence of bile, it was not sufficient to completely rupture the cells. The b-galactosidase remains in the cell having the increased permeability. Bile has a similar effect on Lactobacillus acidophilus in that the permeability of the cells increases
LACTOSE
β-galactosidase
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GLUCOSE + GALACTOSE
Figure 1 Action required by probiotics to provide benefit for lactose maldigestion.
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PROBIOTICS
in the presence of bile enabling lactose to enter more freely and be hydrolyzed. Thus, the mechanism whereby cells of Lactobacillus acidophilus can alleviate the problems of lactose maldigestion is similar to that of yogurt. However, Lactobacillus acidophilus has the added advantage that it can grow in the presence of the bile, and so new cells can be produced during its growth in the intestine, providing even more of the enzyme necessary for hydrolyzing lactose. When preparing a product to which cells Lactobacillus acidophilus are added, it is important that the cells have been grown in a medium containing lactose as a sugar source to insure that cells contain adequate levels of the enzyme b-galactosidase. If not, the amount of enzyme probably will be too low to produce the desired benefit with regard to lactose maldigestion as rapidly as desired.
Hypocholesterolemic Actions 0013
0014
The risk of coronary heart disease in hypercholesterolemic persons can be significantly reduced by lowering serum cholesterol levels. Germ-free animals on an elevated cholesterol diet accumulate approximately twice as much cholesterol in the blood as conventional animals on a similar diet. This suggests the possibility that microorganisms in the intestinal tract can influence serum cholesterol levels. Consumption of organisms such as Lactobacillus acidophilus can aid in the control of serum cholesterol levels in humans. Two studies published in the 1970s showed this to occur. In one of the studies, infants fed a formula supplemented with Lactobacillus acidophilus exhibited reduced serum cholesterol levels associated with increased numbers of lactobacilli in the feces, compared with infants receiving the control formula. This suggests that the lactobacilli may be associated with the reduction of serum cholesterol levels. In another study, a group of men fed milk fermented by the natural flora in raw milk exhibited unexpected reduced serum cholesterol levels. The fermentation apparently included what was described as a culture of Lactobacillus, although the organism was not identified. Because of these studies, considerable research has focused on the potential for Lactobacillus acidophilus or related bacteria to exert beneficial influences on serum cholesterol levels. Lactobacillus acidophilus growing in a laboratory medium supplemented with cholesterol and bile salts under anaerobic conditions will assimilate cholesterol. This ability to assimilate cholesterol varies tremendously among strains of this species of bacteria. Results from a feeding trial using pigs on a high-cholesterol diet as an animal model revealed that supplementation of the diet with a strain
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of Lactobacillus acidophilus that assimilated cholesterol during growth in a laboratory medium had a significant beneficial effect on serum cholesterol, whereas a strain that did not assimilate cholesterol during growth in a laboratory medium did not. This suggests the importance of screening cultures for use as a probiotic to produce a beneficial effect on serum cholesterol levels. In another feeding trial involving pigs with diet-induced hypercholesterolemia, animals receiving cells of Lactobacillus acidophilus exhibited a significant positive correlation between the reduction of serum cholesterol levels and the concentration of cholic acid in the serum. The decline in serum cholesterol was initiated more rapidly and reached a significantly lower level in the animals fed the lactobacilli than in those not fed the lactobacilli. Such data suggest the possibility that the lactobacilli interfered with the enterohepatic circulation of bile acids, which can be an important factor in reducing serum cholesterol levels. This also suggests another activity of the lactobacilli, which may be important in controlling serum cholesterol levels. Lactobacillus acidophilus has the ability to deconjugate bile acids through the action of bile salt hydrolase. Free bile acids being less well absorbed from the small intestine than conjugated acids are more likely to be excreted from the body. Replacement of these excreted bile acids involves the synthesis of new bile acids from cholesterol in the body. This has a tendency to lower the cholesterol pool in the body. This represents the major pathway for removing cholesterol from the human body. An additional advantage for the deconjugation is that free bile acids do not support the absorption of cholesterol for the intestinal tract as well as conjugated acids. The mechanism whereby consumption of fermented milk products containing cells of Lactobacillus acidophilus or other probiotics may reduce levels of serum cholesterol appears to include their ability to assimilate cholesterol and/or deconjugate bile acids (Table 4). Some of the cholesterol assimilated by Lactobacillus acidophilus is incorporated in the cellular membranes of the organisms. Bifidobacterium longum also can incorporate some cholesterol into its membrane, but Lactobacillus casei does not. All three species have the ability to deconjugate bile salts.
Table 4 Activities of probiotic cultures important for imparting a hypocholesterolemic effect . Assimilation of cholesterol . Deconjugation of bile salts
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Control of Colon Cancer 0016
0017
Some lactic acid bacteria can produce anticarcinogenic or antimutagenic compounds, which can result in the inhibition of some types of tumor cells in animals. For example, rats that had been implanted with ascites tumor cells and fed milk fermented with Lactobacillus acidophilus exhibited a lower proliferation of tumor cells than those in the control group. The conclusion was that the Lactobacillus species produced substances during growth in the intestine that was antagonistic toward the proliferation of these tumor cells. Other studies have shown that certain fermented milks have a beneficial influence on the proliferation of colon tumor cells in rats. Feeding rats cells of Lactobacillus reduced the activity of three enzymes capable of converting procarcinogens into carcinogens in the intestinal tract. Similar results have been shown in human studies. These enzymes were bglucuronidase, azoreductase, and nitroreductase. Reduction of the level of activity of these enzymes in the intestinal tract can reduce the chances of carcinogens being formed. The enzymes apparently are of microbial origin. Thus, the potential anticarcinogenic activity of feeding Lactobacillus acidophilus may, in this case, be related to the control of undesirable microorganisms in the intestinal tract. In other studies, the consumption of milk containing cells of Lactobacillus casei activated macrophages in mice. This observation was based on increases in enzyme activity associated with macrophages. This suggests another potential means, whereby the consumption of a selected probiotic culture may influence proliferation of tumor cells in the body.
Other Benefits 0018
One of the main interests in the livestock industry in using probiotic bacteria as feed supplements is to improve nutrient utilization resulting in improved growth and/or feed efficiency of the livestock. While there is great interest in this area, there is very little evidence reported in the scientific literature to indicate how such benefits might occur. It is possible that such benefits can result from the action of certain enzymes associated with the probiotic bacteria. This could be similar, for instance, to the beneficial effect of yogurt bacteria and Lactobacillus acidophilus on lactose maldigestion in humans that results from b-galactosidase associated with the bacterial cells. Selection of a culture of Lactobacillus acidophilus with a high level of amylase activity for inclusion as a probiotic in the diet of young pigs can improve starch utilization in the young animal. In a feeding
trial involving the use of such a culture, improved growth and feed efficiency of weaning aged pigs were observed as a result of including the selected culture in the diet. The benefit was attributed to the amylase activity of the culture. It is possible that other enzymes that could improve the digestion of other nutrients may be present in some bacteria used as probiotics that could result in improved growth and feed efficiency of the livestock. Of course, the improved growth may relate to the control of undesirable microorganisms in the animal’s intestinal tract. There is also interest in the livestock and pet-food industries in using probiotics to help control intestinal infections in animals.
Selection of Probiotic Culture While there are a number of potential benefits from the inclusion of a probiotic culture in the diet, it is essential that a culture be properly selected for such use. One culture, that is one strain of one species, should not be expected to provide all of the potential benefits that might be derived from probiotics. To help insure that the culture is successful and has a positive effect, certain requirements are to be met (Table 5). Since, in most cases, the sight of action of the probiotic organisms is the intestinal tract, it is generally accepted that the organism should be a normal inhabitant of the intestinal tract. There is strong evidence in the literature indicating that many of these probiotic bacteria exhibit host specificity; for example, a strain of Lactobacillus acidophilus originating in the intestinal tract of a calf should not be expected to function equally well in the intestinal tract of a pig or of a human. Thus, it is desirable to use a selected strain of bacteria that originated in the host species for which the product is to be used. If it is to be used as a probiotic for humans, it is highly desirable that the probiotic organism originated in the human intestines. In order to avoid problems with regulatory agencies, it is desirable that the organism of choice has a history of having been used for producing fermented food products.
Table 5 Important factors to consider in selection of a probiotic culture . . . . . . .
Normal inhabitant of intestine Host specificity Acid tolerance Bile tolerance Stability during production and delivery Production of desired health/nutritional benefit One strain would be unlikely to provide all possible benefits
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0020
The organism should be resistant to gastric acidity to survive passage through the stomach. The main organisms considered for use as probiotics (i.e., lactobacilli) are acid-tolerant. However, resistance to acidity varies among strains and species, so it must be considered. If the organism is expected to grow and function in the intestinal tract, it must have a certain degree of bile tolerance. The bile resistance based on the ability of the organism to grow in the presence of bile acids varies tremendously among strains of each species of probiotic bacteria. The minimum level of bile tolerance required is not known, but it is suggested that the most bile-resistant strain that will provide the desired benefit be selected. The probiotic culture must be stable during production and storage of the food or feed containing it. This is often the most challenging factor in providing a probiotic organism that has adequate levels of viability at the time of consumption. The most important characteristic of course is that the probiotic culture produce the desired effect. Therefore, it is desirable that some sort of laboratory screening test for the desired effect be implemented. This is not always easy. However, if the organism for instance is to be used for improving lactose utilization, it would be desirable to select one having a high level of b-galactosidase activity. If it is to be used for controlling serum cholesterol levels, it is desirable that the organism not only assimilate cholesterol but also have a high degree of ability to deconjugate bile acids. In order to develop useful screening tests, it is of course essential that we understand how the probiotic organism functions to provide the desirable benefit. In many cases, we simply do not know the answer to this mechanism at this point. A major factor in selection of a specific organism for use as a probiotic is to remember that one strain should not be expected to provide all potential benefits. Far more is required in the selection process than to select a culture just because it is Lactobacillus acidophilus, for example. There is a great variation among strains of this bacterial species. Such variation also occurs among strains of other species of probiotic bacteria.
Dietary Delivery of the Probiotic 0021
If the probiotic organism is expected to provide its benefit during growth and action in the intestinal tract, it is reasonable to assume that the organism must be viable at the time of consumption. It is also desirable and recommended that the probiotic be consumed on a continuing basis. The numbers of viable probiotic bacteria required in a food or feed product to provide the benefit are not known. The
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actual numbers required probably will vary with the organism and the expected function. Some have suggested, particularly with regard to milk products, that the probiotic should be present at a level of one to two million per milliliter; however, these numbers are not based on scientific data but are based more on an economic situation reflecting the cost of the organism. Research is needed to answer the question with regard to the optimum numbers required. It is essential that the organism be stable and that the desired characteristics be maintained during the production of the probiotic culture, during its storage, and delivery in the food or feed. This is often the greatest challenge in the use of probiotic bacteria. The stability of the organism during storage and delivery can be greatly influenced by the conditions under which the bacteria are grown. For instance, the growth of Lactobacillus acidophilus at pH 5 has resulted in cultures that are more stable during storage when added to refrigerated milk than the same cultures grown at a higher pH. The storage stability, especially during frozen and refrigerated storage, varies among strains of a given bacterial species used as a probiotic. Thus, this becomes a factor to consider in selecting the organism for use as a probiotic. The use of probiotic bacteria such as Lactobacillus acidophilus in conjunction with yogurt can be accomplished by either including the probiotic as part of the starter culture or adding cells of the probiotic bacteria after the product has been manufactured. Of course, it would be desirable to use the probiotic as part of the inoculum (i.e., starter culture) used in the manufacture of yogurt in order to yield higher numbers of the probiotic bacteria during the incubation period for the fermentation. However, most of the probiotic bacteria do not grow well under such conditions, and very little increase in numbers is achieved during the incubation process involved in the manufacture of yogurt. Research is needed to provide means of increasing the numbers of probiotic bacteria that grow during the manufacture of a product such as yogurt when the organism is used as a part of the inoculum for manufacturing the fermented milk. In summary, once a desired probiotic culture has been selected, it is important to develop procedures for producing the culture, storing the culture, and delivering the culture in the food or feed without damaging the desired characteristics. See also: Bifidobacteria in Foods; Cholesterol: Properties and Determination; Role of Cholesterol in Heart Disease; Colon: Cancer of the Colon; Immunology of Food; Lactic Acid Bacteria; Lactose; Salmonella: Salmonellosis; Staphylococcus: Food Poisoning
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Further Reading Bezkorovainy A and Catchpole RM (1989) Biochemistry and Physiology of Bifidobacteria. Boca Raton, FL: CRC Press. Fuller R (ed.) (1992) Probiotics the Scientific Basis. New York: Chapman & Hall. Gilliland SE (1990) Health and nutritional benefits from lactic acid bacteria. FEMS Microbiology Reviews 87: 175–188. Klein G, Pack A, Bonaparte C and Renter G (1998) Taxonomy and physiology of probiotic lactic acid bacteria. International Journal of Food Microbiology 41: 103–125.
Ouwehand AC, Kirjavainen PV, Shortt C and Salminen S (1999) Probiotics: mechanisms and established effects. International Dairy Journal 9: 43–52. Robinson RK (ed.) (1991) Therapeutic Properties of Fermented Milks. Barking, UK: Elsevier Science. Sissons JW (1989) Potential of probiotic organisms to prevent diarrhoea and promote digestion in farm animals – a review. Journal of the Science of Food and Agriculture 49: 1–13. Tamine AY and Robinson RK (1999) Yoghurt Science and Technology, 2nd edn. Boca Raton, FL: CRC Press.
Process Control See Plant Design: Basic Principles; Designing for Hygienic Operation; Process Control and Automation; Instrumentation and Process Control
Processed Cheese See Cheeses: Types of Cheese; Starter Cultures Employed in Cheese-making; Chemistry and Microbiology of Maturation; Manufacture of Extra-hard Cheeses; Manufacture of Hard and Semihard Varieties of Cheese; Cheeses with ‘Eyes‘; Soft and Special Varieties; White Brined Varieties; Quarg and Fromage Frais; Processed Cheese; Dietary Importance; Mold-ripened Cheeses: Stilton and Related Varieties; Surface Mold-ripened Cheese Varieties; Risk Assessment
PROSTAGLANDINS AND LEUKOTRIENES S Katayama, Saitama Medical School, Iruma-gun, Saitama, Japan J B Lee, State University of New York, New York, USA Copyright 2003, Elsevier Science Ltd. All Rights Reserved.
Background 0001
Prostaglandins (PGs) were discovered in the 1930s and were first chemically isolated and identified in sheep seminal vesicles and renal medulla in the 1960s. Although together with thromboxanes (TXs) and leukotrienes (LTs), the PGs possess the most potent and most divergent biological activities of any naturally occurring compounds, their true physiological role in many instances remains unknown. From a pathophysiological viewpont, an absolute or relative deficiency of PGs relative to TXs has been implicated in the etiology of hypertension, thrombosis, and
atherogenesis for many years. Since PGs and TXs are derived from essential fatty acids, the role of dietary intake of these fatty acids in PG and TX production, particularly in relation to cardiovascular system, will be examined. The possible role of dietary essential fatty acids on LT and PG production in relation to inflammation, the immune system, and gastric function will also be discussed.
Chemistry In the 1930s, it was reported that fresh human semen causes rhythmic contractions of human endometrium. The active substance was called ‘prostaglandin.‘ In the 1960s, PG was determined to be a mixture of biologically active compounds, which were isolated from sheep seminal vesicles and identified as PGE1–3 and PGF1–2. These compounds were independently isolated from extracts of rabbit kidney
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