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8.1 Introduction
Functional foods are food choices that provide additional benefits to human physiology and metabolic activities. The probiotic effects of fermented dairy products have been examined in an increasing num- ber of recent studies. Kefir, which contains probiotic microorganisms and has a complex structure, is the most interesting beverage among these products (Köroğlu et al., 2015). The term kefir comes from the Turkish word keyif (pleasure) to indicate pleasure after drinking (Esmek and Güzeler, 2015). Kefir is one of the most important pro- biotic products considered as a strong supplement. It is a fermented dairy product that is yellowish or white, sour, acidic, and viscous; it contains a slight amount of alcohol. Kefir is produced by the fermen- tation of traditional or commercial semiskimmed or skimmed milk (goat, cow, sheep, and camel milk) with kefir particles (Sharifi et al., 2017). Turkish Food Codex kefir is defined as a fermented dairy prod- uct, and starter cultures or kefir particles including the yeast types that ferment lactose (Kluyveromyces marxianus) with the different strains of Lactobacillus kefir and Leuconostoc, Lactococcus, and Acetobacter types and those that do not ferment lactose (Saccharomyces unispo- rus, Saccharomyces cerevisiae and Saccharomyces exiguus) are used for the fermentation process of this kefir type (Turkish Food Codex, 2009).
Kefir fermentation occurs with lactic acid and alcohol fermentation, and yeasts and lactic acid bacteria are in a symbiotic relationship and responsible for the fermentation (Karabıyıklı and Daştan, 2016). The variation, type, and number of the population in the microflora of kefir particles, biochemical characteristics, and microbiological profile of the milk used or the physical or geographical differences regarding the method used in production cause differences in the color, taste, smell, and chemical or microbial context of the end product (Karabıyıklı and Daştan, 2016).
KEFIR BEVERAGE AND ITS EFFECTS ON HEALTH
Nalan Hakime No ğ ay
Faculty of Health Science, Department of Nutrition and Dietetics, Erciyes University, Kayseri, Turkey
8
Fermented elements produced by lactic acid bacteria have a bene- ficial effect on the specific or nonspecific immune response of humans and animals (Ahmed et al., 2013). In addition, different studies have shown that kefir has anticarcinogenic and antiallergic effects, regu- lates the immune system, lowers cholesterol and blood pressure lev- els, regulates the blood glucose level, acts as an antimicrobial, and has positive effects on lactose intolerance and the gastrointestinal system (Köroğlu et al., 2015). This chapter will focus on the composition of kefir and its effects on health.
8.2 Microbiological Characteristics of Kefir
Kefir particles consist of lactic acid bacteria, acetic acid bacteria, and yeasts. The particles used in kefir production include an inert polysaccharide/protein matrix and a glucose-related structure that hosts bacteria and small (3–20 mm in diameter) irregularly shaped yeasts that look like cauliflower or popcorn (Karabıyıklı and Daştan, 2016). Kefiran, which constitutes at least 25% of kefir particles, con- sists of 30%–34% casein, 45%–60% saccharide, 3%–4% fat, living and dead microorganisms, and equal amounts of glucose and galactose (Karatepe et al., 2012).
Kefir particles consist of yeast (Kluyveromyces, Candida, Torulopsis, and Saccharomyces spp.) lactobacilli (L. brevis, L. acidophilus, L. casei, L. helveticus, and L. delbruckii), streptococci (Streptococcus salivarus), lactococci (L. lactis ssp. thermophilus, Leuconostoc mesen- teroides, and L. cremoris) and a slight amount of acetic acid bacteria.
Homofermentative lactobacillus constitutes the most important part of the bacterial flora. L. kefiranofaciens, a new lactobacillus type, has been recognized recently; the outer polysaccharide layer of kefir parti- cle is produced by this bacterium (Karatepe et al., 2012).
Lactobacillus generally constitutes 65%–80% of the granule mi- croflora. The rest consists of Streptococcus (20%) and yeasts (5%) (Karatepe et al., 2012). Lactococcus types grow faster in milk than in yeast. Lactococcus hydrolyzes lactose and produces lactic acid, thereby ensuring the optimal environment for yeast growth. Yeasts synthesize complex vitamin B types and hydrolyze milk proteins to produce CO2 and ethanol using oxygen. The interaction between yeast and lactic acid bacteria may be prevented or stimulated with the growth of one or both (Leite et al., 2013b).
Exopolysaccharides (EPS) are polysaccharides synthesized on the outside of the cells by microorganisms. EPS produced by kefir micro- organisms have antioxidant, antiinflammatory, and positive effects on key organisms in the intestines. EPS, produced by Weissella cibaria and Pediococcus pentosaceus, displays a strong reactivity in diges- tion in the stomach and intestines. The EPS type that is produced by
Lactobacillus plantarum DM5 inhibits the growth of nonprobiotic bacteria. In a study conducted on mice to determine the effect of the EPS type that is produced by Lactobacillus plantarum YW11 on the level of intestinal microbiota, it was found that EPS increased glutathi- one peroxidase (GSH-Px), superoxide dismutase, catalase (CAT), and total antioxidant capacity, reduced oxidative stress and Flexispira den- sity, and boosted Blautia density and the amount of short chain fatty acids (Zhang et al., 2016).
Lactic acid bacteria in kefir are added to milk to assist in initiat- ing the fermentation. These microorganisms produce lactic acid from lactose and lower the pH level. Lactic acid bacteria are responsible for certain main characteristics of fermented milk such as taste and long shelf life. For the production of fermented milk, Lactobacillus, Streptococcus, Leuconostoc, Pediococcus, and Lactococcus genera are used (Karatepe et al., 2012).
Yeasts have an important role in kefir fermentation because they produce ethanol and CO2. Yeasts are also important for the symbiosis between the microorganisms of kefir particles, improving the authen- tic aroma and taste of kefir. Kefir particles generally contain lactose- fermented yeasts (Kluyveromyces lactis, Kluyveromyces marxianus, and Torula kefir) and nonlactose fermented yeasts (Saccharomyces cerevisiae). In dairy products, yeasts are some of the most important causes of spoilage. Yeasts provide a small contribution to the fermen- tation of kefir and kumis (Karatepe et al., 2012).
The microbial composition of kefir varies by the production method and culture used (Arslan, 2015). In addition, factors such as kefir particle to milk ratio, incubation time and temperature, sanitation during the separation of kefir particles, how the particles are washed and stored significantly affect kefir quality and microflora of kefir par- ticles (Gao and Li, 2016). A study conducted with Brazil kefir indicated that the number of lactic acid bacteria was higher than that of yeasts and acetic acid bacteria following the fermentation. During the stor- age phase, the amount of lactic acid bacteria and yeasts was constant, but the amount of acetic acid bacteria increased. The same study sug- gested that the lactose content, pH level, and citric acid amount de- creased and glucose, galactose, ethanol, butyric acid, propionic acid, and acetic acid amounts increased during the time from fermentation to the end of the storage phase (Leite et al., 2013a). In another study that examined the microbiologic quality of 50 kefir samples and cer- tain chemical characteristics, the amounts of lactobacilli, lactococci, enterococci, Enterobacteriacea, Staphylococcus aureus, and yeast, re- spectively, were found as follows: 3.6 × 107, 1.8 × 108, 4.8 × 104, 7.3 × 103, 2.4 × 102, and 7.7 × 104 cfu/mL. In addition, the pH value of the kefir samples changed between 3.9 and 4.7, and Escherichia coli was found in 22%. The same study suggested kefir samples can be contaminated
with significant bacterial pathogens, and that good hygiene practices should be performed during production as there may be a health risk (Cetınkaya et al., 2012).
8.3 Nutritional Composition
Kefir contains not only the basic nutritional elements, but also high amounts of amino acids, protein, phosphorus, and calcium (Ahmed et al., 2013). The chemical composition of kefir is as follows: 90% wa- ter, 6% carbohydrate, 3.5% fat, 3% protein, and 0.7% ash. Serine, lysine, alanine, threonine, tryptophan, valine, methionine, phenylalanine, and isoleucine are higher in kefir in comparison with nonfermented milk (Rosa et al., 2017).
Kefir is rich in vitamins; the vitamin content will vary with the quality of the milk used, microorganisms found in kefir particles, and preparation method. Kefir contains thiamine, riboflavin, and vi- tamins C, A, K, and carotenes (Köroğlu et al., 2015). The production of some compounds such as pyridoxine, vitamin B12, folic acid, and biotin increases during the fermentation process, and the amounts of riboflavin and thiamine decrease (Esmek and Güzeler, 2015). Some re- searchers suggest that the amount of vitamin B12 also decreases during this stage, which may result from the selectivity of specific microflora in kefir particles (Guzel-Seydim et al., 2000).
Kefir is a good source of minerals such as magnesium, calcium, and phosphorus. In addition, it contains other minerals such as zinc, copper, iron, cobalt, and manganese (Rosa et al., 2017).
The lipid content of kefir varies by the type of milk used for fermen- tation (Rosa et al., 2017). The sugar found in kefir, kefiran, is a hetero- polysaccharide (Ahmed et al., 2013). Kefiran reduces the viscosity of kefir; it has useful physicochemical qualities, such as improving the rheological characteristics (Sharifi et al., 2017).
Lactic acid, CO2, and ethanol are the main components of the lactic fermentation process. Kefir also contains aldehydes, isoamyl alcohol, and formic, succinic, and propionic acids. The ethanol con- tent of kefir varies between 0.5% and 2%, and its pH level between 4.2 and 4.6. Kefir contains biogenic amines such as tyramine, cadaver- ine, and putrescine produced by lactic acid bacteria (Arslan, 2015).
High amounts of biogenic amines negatively affect the sensory char- acteristics of kefir. Thus, the level of these biogenic amines is consid- ered as a significant indicator of kefir quality and acceptability (Rosa et al., 2017).
In a study conducted to determine the effect of kefir fermentation on kefir characteristics, the effects of different goat and cow species and different nutritional habits on mineral, vitamin, and chemical characteristics were examined. It was found that the kefir made from
Hair goat milk had more vitamins and minerals than that made from the milk of other goat and cow species (Saanen goat milk and Holstein cow milk) (Satir and Guzel-Seydim, 2016).
8.4 Kefir Production
Different methods can be used for kefir production, but traditional and industrial methods are generally preferred. Any milk type (goat, cow, sheep, rice, soy, etc.) can be used for kefir production (Otles and Cagindi, 2003). Traditional kefir production is performed by adding kefir particles directly to milk. Raw milk is boiled and cooled to 20–
25°C. Kefir particles are added at 2%–10% (usually, 5%), and the mix- ture is left to ferment. After 18–24 h, kefir particles are separated from milk using a colander. These kefir particles are stored at 4°C until the next inoculation (Otles and Cagindi, 2003).
Different methods are more common in industrial kefir produc- tion, but the basic principles are generally the same. The milk to be used for industrial kefir production passes through microbiological and chemical controls. It is homogenized and heated at 90–95°C with 8% dry content for 5 or 10 min. Afterward, it is cooled to 18–
24°C and left to ferment with kefir particles at 2%–8%. Following the fermentation process, which lasts 18–24 h, kefir is bottled, matured at 3–10°C, and stored at 4°C (Otles and Cagindi, 2003). Lyophilized (freeze-dried) culture use began to be common to reduce the risk of contamination as industrial kefir production increased (Hertzler and Clancy, 2003).
Different methods are used to store kefir particles. Freezing, ly- ophilization, air drying, and storing under refrigeration are among them. Traditional kefir particles can maintain their activity for 12–
18 months due to air drying and lyophilization methods. Kefir parti- cles can maintain their microbial activities for 7–8 months if stored at
−20°C. However, their activities decrease after approximately 10 days (Turan and Ilter, 2007). Dried particles can retain activity for 12–
18 months. Excessive washing and misuse can change the quality of the end product and the microbiota of the particles. Kefir particles can be dried for 36–48 h at room temperature and stored in a cold and dry place or by freezing for long-term storage (Altay et al., 2013).
8.5 Effects of Kefir on Health
Kefir has prophylactic, recuperative, and many other significant physiological effects on health. These effects emerge through the ef- fects of the many bioactive components produced during fermenta- tion and the dense microbiota (Rosa et al., 2017).
8.5.1 antimicrobial characteristics of Kefir
Organisms in kefir produce many antimicrobial elements such as lactic acid, acetic acid, carbon dioxide, hydrogen peroxide, ethanol, diacetyl, and bacteriosins (Nielsen et al., 2014). Kefir displays its anti- bacterial effect thanks to these organic acids, hydrogen peroxide, car- bon dioxide, bacteriosins, and acetaldehyde (John and Deeseenthum, 2015). In a study, bacteriosin produced by Lactobacillus plantarum inhibited Gram-negative and Gram-positive bacteria (Powell et al., 2007). Kefir displays a bactericidal effect on Gram-negative bacteria.
This effect was also found against Salmonella, Shigella, Staphylococcus, Helicobacter pylori, E. coli, Enterobacter aerogenes, Streptococcus pyogenes bacteria and Candida albicans fungi. The antibacterial ac- tivity of the kefir particles is higher than the kefir itself against Gram- positive cocci containing Gram-positive bacilli and staphylococci. It was found that fresh kefir inhibited Staphylococcus aureus and E. coli, but no inhibiting effect was found against Saccharomyces cerevisiae and Candida albicans. Kefir lost this effect following reemergence and lyophilization in milk (Rosa et al., 2017). In addition to S. thermophilus isolated from kefir, L. acidophilus and L. kefiranofaciens types display antimicrobial activity against pathogenic organisms such as E. coli, L.
monocytogenes, S. aureus, S. typhimurium, S. enteritidis, and S. flexneri (Bourrie et al., 2016).
8.5.2 antihypertensive effect
The kidneys play an important role in many bodily functions, in- cluding balancing electrolyte levels and regulating blood pressure. If kidney veins are damaged, excess water may not be eliminated from the body, causing an increase in blood pressure. The blood pressure level of many hypertensive people is sensitive to increases in dietary salt and total body sodium. An increase in dietary NaCl intake causes further increases in body weight, extracellular fluid volume, and plasma volume. In addition, it causes decreases in plasma rennin, an- giotensin, and norepinephrine levels. Rats were administered a high- salt diet for 4 weeks to examine the effect of kefir on blood pressure and it was found that the cathepsin B level of the group to which kefir was administered significantly decreased, creatinine clearance was higher, and kefir reduced the harm to renal function as angiotensin converter enzyme (ACE) inhibitor (Kanbak et al., 2014).
Studies suggested that kefir might inhibit the activity of ACE via the effect of the bioactive peptides produced from casein during fer- mentation (Quirós et al., 2005). ACE inhibitor peptides inhibit the destruction of bradykinin, a hormone that assists in blood pressure reduction. ACE peptides reduce the formation of angiotensin-I and aldosterone (Rosa et al., 2017). In a study in which hypertensive rats
were administered kefir (0.3 mL/100 g) for 60 days, blood pressure de- creased by 15% (Friques et al., 2015).
8.5.3 Hypocholesterolemic effects
Cardiovascular diseases are among the most common reasons for death; a high serum cholesterol level is an important risk factor.
Diet plays a significant role in managing the serum cholesterol level.
Studies have suggested that fermented milk may reduce the serum cholesterol level (Bourrie et al., 2016). Consumption of probiotic milk products is also recommended as a way to reduce the cholesterol level.
Lactic acid, which inhibits the bacteria in small intestines by binding the hexogen cholesterol, is plentiful in kefir and can directly or indi- rectly reduce the cholesterol level by 33% (Rosa et al., 2017).
Probiotic bacteria boost the production of short chain fatty acids;
among them, propionate hydroxymethylglutaryl CoA (HMG-CoA), a short chain fatty acid, inhibits reductase activity and reduces cho- lesterol production. In addition, propionate inhibits the intestinal ex- pression of the genes that are necessary for cholesterol biosynthesis and causes kefir to display a hypocholesterolemic effect (Rosa et al., 2017). Lactobacillus plantarum MA2, isolated from kefir, was found to reduce total serum cholesterol, triglycerides, and LDL cholesterol of rats consuming a high cholesterol diet (Wang et al., 2009).
Kefir particles can reduce the cholesterol level of milk during the fermentation process (Bourrie et al., 2016). Bacteria in kefir decon- jugate bile salts and reduce serum cholesterol levels. Lactobacillus spp. produces the bile salt hydrolase (BSH) enzyme, ensuring decon- jugation. BSH activity deconjugates bile salt. The solubility of decon- jugated bile acids is lower, and fewer of these acids are absorbed by the intestines, causing an increased discharge of bile acids from the intestine channel. The liver uses the present cholesterol level in the body and synthesizes more bile acid. Thus, cholesterol, the main el- ement of bile acids, is used more and the serum cholesterol level de- creases (Alp and Ertürkmen, 2017). In a study conducted to assess the lipid-lowering effect of kefir drinks, 75 overweight or obese women whose ages ranged from 25 to 45 were randomly separated into three groups. For 8 weeks, the first group was administered four portions of kefir, the second group consumed four portions of milk, and the third group drank two portions of low-fat milk each day. Serum lipoprotein levels and rates of the group consuming kefir were significantly lower than those of the control group, but no significant difference was pres- ent between the groups consuming milk and kefir (Fathi et al., 2017).
In a study conducted in slightly hypercholesterolemic males who were administered kefir for 4 weeks, it was found that kefir did not cause a significant change in total serum cholesterol, HDL cholesterol,
triglyceride, and LDL cholesterol levels (St-Onge et al., 2002). Another study indicated that kefir reduced triaxial glycerol, total cholesterol, and LDL cholesterol levels of mice consuming a high-fat diet. This is presumed to arise from an inhibition of intestinal lipid absorption (Choi et al., 2017).
Kefir reduces cardiac and vascular sympathetic hyperactivity and strengthens cardiac parasympathetic hypoactivity (Klippel et al., 2016).
8.5.4 its effects on lactose intolerance
Dairy products contain high amount of lactose, a disaccharide;
intestinal absorption of lactose requires the hydrolysis of this com- pound. Some persons may suffer from lactose intolerance due to the lack of intestinal β-galactosidase enzyme activity. The β-galactosidase enzyme is naturally present in kefir particles. In addition, lactose con- tent in kefir decreases during fermentation and kefir becomes suitable for those who have lactose intolerance. Kefir delays gastric discharge and helps in the digestion of lactose (Rosa et al., 2017). A study con- ducted on this issue suggested that kefir consumption reduced lactose intolerance in adults (Hertzler and Clancy, 2003).
8.5.5 antiinflammatory effect
A direct or indirect antiinflammatory effect on microbiota arises from the bioactive components produced during fermentation (Rosa et al., 2017). Bioactive peptides in kefir cause macrophage activation, nitric oxide (NO) formation, and phagocytosis. In addition, they in- crease the secretions of TNF-α and cytokine and decrease IL-8 secre- tion. An increase in the level of IL-5, a cytokine, increases IgA secretion.
A decrease in the IL-8 level represses neutrophil activities and controls the inflammatory response (Sharifi et al., 2017). A study conducted in septic rats to determine whether kefir prevents organ dysfunction sug- gested that kefir reduces organ dysfunction in experimental sepsis and may be a beneficial treatment for organ dysfunction related to sepsis or local systemic inflammation (Öresin, 2008).
Angiogenesis is the formation of new veining from already exist- ing veins. Angiogenesis is very important for tissue repair and devel- opment such as hair growth, development of colorectal circulation in the ischemic tissues in the corpus luteum, wound healing, and endo- metrium and placenta formation. Tissue stimulation and expression of proangiogenetic factors must increase for angiogenesis to occur.
Hyaluronidase enzyme ensures that a cell is connected to another cell; it can stimulate inflammation but can be inhibited by chemicals or natural inhibitors (phenolic compositions and flavonoids). A study conducted to determine the antiinflammatory and angiogenic activity of polysaccharide extract produced by the fermentation of Tibet kefir
indicated that kefir polysaccharide extract inhibited hyaluronidase enzyme and that kefir polysaccharide extract can be safely used for pharmacologic purposes (Prado et al., 2016).
Acute spinal cord injury is a significant cause of morbidity and mortality. Secondary injury follows the initial injury in acute spinal cord injuries; this leads to cellular death. The amount of free oxygen radicals is increased by secondary injury, and endogenous radical scavengers become insufficient. The central nervous system is very sensitive to increased lipid peroxidation; it increases with the free radicals that increase with acute spinal cord injuries. Simultaneously, MDA (malondialdehyde) values increase. A study conducted to deter- mine the effect of kefir on lipid peroxidation that plays a significant role in spinal cord trauma indicated that MDA values significantly de- creased, while cathepsin B values increased, in the study group con- suming kefir. Thus, by virtue of its antioxidant and antiinflammatory characteristics, kefir may help prevent secondary injuries in acute spi- nal cord injuries (Delen et al., 2015). A study conducted with rats to determine the effects of kefir on lipid peroxidation and certain antiox- idant enzyme systems indicated that the MDA level was significantly lowered in the group administered kefir, but the frequency of glutathi- one (GSH), GSH-Px, and CAT activity was high. It was found that kefir was effective in reducing lipid peroxidation (Güven et al., 2004).
Mast cells play an important role in allergic and inflammatory dis- eases. In a study conducted to examine the effect of kefiran on mast cell activation in response to antigens, kefiran repressed mast cell degran- ulation and cytokine production and displayed an antiinflammatory effect (Furuno and Nakanishi, 2012). Corrosive esophageal injury is an important health problem for the pediatric age group. The general reason for this type of injury is based on alkaline substances such as potassium and sodium. These substances may cause great damage to the mucosal surface. In addition, regarding long-term complications, they may cause esophageal cancer. Kefir reduced the total number of inflammatory cells and free oxygen radicals in rats that had developed corrosive esophagitis (Yasar et al., 2013).
8.5.6 anticarcinogenic effects
The anticarcinogenic characteristic of kefir is related to its bioac- tive components, such as peptides, polysaccharides, and sphingolip- ids. These bioactive components have important roles in regulating cellular processes—cellular proliferation, apoptosis, and transforma- tion (Rafie et al., 2015). The regular consumption of kefir may posi- tively affect the composition of the immune system and intestinal microbiota. Lactobacilli play an important role in the antitumor ef- fect of kefir (Ahmed et al., 2013). Studies indicated that effervescent
polysaccharides in kefir particles displayed a protective effect against lung metastasis in rats, and that noneffervescent polysaccharides pre- vented skin metastasis (Lopitz-Otsoa et al., 2006). One of the mecha- nisms of the anticarcinogenic effect is the decrease in TNF-α, TNF-β, and Bc12 secretion. Low TNF-α and TNF-β secretion produces an an- tiproliferative effect against cancer cells. In addition, the sphingomye- lins in kefir increase the secretion of interferon-β (Sharifi et al., 2017).
Dietary components play an important role in protecting the body against oxidative damage. Kefir contains many components with an- tioxidant activity (Ahmed et al., 2013). This effect increases the GSH- Px level and reduces the malondialdehyde level. Kefir can also bind 1,1- diphenyl-2-picrylhydrazyl (DPPH) and superoxide radicals, and inhibit linoleic acid peroxidation (Sharifi et al., 2017). A study con- ducted to determine the antioxidant capacity of kefir made from goat milk indicated that the total phenolic content significantly decreased as the fermentation duration increased, and this content reached its highest level at the fourteenth day in terms of storage duration (Yilmaz- Ersan et al., 2016). Another study conducted with mice exposed to carbon tetrachloride, a hepatotoxic causing oxidative harm, suggested that kefir reduced the malondialdehyde levels in the liver and kidney.
This is thought to be the result of the antioxidant characteristics of ke- fir. The same study showed that kefir was more effective than vitamin E in fighting against oxidative hazards (Güven et al., 2003).
Kefir was found to suppress morphological changes in melanoma cells. In addition, administering kefir extract resulted in a significant decrease in intracellular reactive oxygen species (ROS) (Sharifi et al., 2017). Some studies have indicated that kefir consumption increases the apoptosis rate and decreased cellular proliferation in leukemia. In addition, kefir displayed a proapoptotic effect on cancer cells, but it did not cause any necrotic effect on normal cells (Jalali et al., 2016; Maalouf et al., 2011). Similarly, another study found that kefir caused apopto- sis in gastric cancer cells. Apoptosis is related to the decrease in the polarization of mitochondrial membrane potential (MMP) (Ghoneum and Felo, 2015). In a study conducted to evaluate the anticarcinogenic effect of kefir on the human colon, kefir displayed a protective effect against DNA damage caused by carcinogen agents. DNA damage is a critical issue in carcinogenesis; thus, kefir was thought to reduce the risk of colon cancer with this anticarcinogenic effect (Grishina et al., 2011). A study performed to determine the effect of kefir on the side effects of chemotherapy in colorectal cancer patients suggested that consuming 500 mL kefir daily during the whole chemotherapy process had no effect on the gastrointestinal side effects of chemotherapy such as nausea, vomiting, and constipation, but that it relieved the sleeping problems patients suffered (Can et al., 2009). Another study indicated that kefir has an anticarcinogenic effect against human sarcoma cells
(Alsha'ar et al., 2017). In addition, a study conducted to evaluate the anticarcinogenic effect of kefir and ayran, another fermented drink, found that their consumption reduced DNA loss, presumably related to the antioxidant characteristics of acetic and lactic acid in these bev- erages (Grishina et al., 2011).
8.5.7 its effects on the immune system
There is no direct relationship between nutrition and the immune system. Another reason for the source for kefir’s activity in the im- mune system is the sphingomyelin isolated from its lipids. After the intake of lactic acid bacteria in kefir, immune activities were observed in humans and various animals, and lactic acid bacteria were found to boost the resistance to infections seen in both humans and animals.
The effect of lactic acid bacteria on the immune system can easily be observed after oral or parenteral administration (Karatepe and Yalçın, 2014). These microorganisms provide beneficial effects either by di- rectly maintaining the activity of microbial cells or indirectly through metabolites. The rate of pathogenic activity of pulmonary and perito- neal macrophages is reduced after the consumption of kefir. These re- sponses can affect the mucosal response in various areas of the body.
The microflora in kefir can modify innate immunity by altering the cytokine response (Ahmed et al., 2013). In a study conducted to de- termine the immunomodulatory effect of kefir, 18 healthy volunteers (ages 20–40 years) followed a diet that did not contain any fermented products for 2 weeks and then consumed 200 mL of kefir daily for 6 weeks. Serum IL-8 levels decreased in the third and sixth weeks com- pared with the beginning, and IL-5 levels increased in the third week.
TNF-α levels increased with kefir consumption; however, a statistically significant increase took place only in the sixth week. Consumption of kefir increased the polarization to the Th1-type immune response and repressed the allergic response (Adiloğlu et al., 2013). During the fermentation of kefir, proteolysis of milk casein takes place. Peptidic fractions are thought to stimulate the growth of kefir bacteria and im- prove the immune system (Turan and Ilter, 2007). Another reason why kefir stimulates the immune system is based on the activation of exo- polysaccharides in kefir particles (Farnworth, 2005).
Giardiasis, caused by Giardia intestinalis, is one of the most common intestinal diseases. This parasite can affect children and adults and cause diarrhea, malabsorption, loss of weight, and growth retardation. A study conducted in rats to determine whether or not kefir has a protective ef- fect on the infection caused by giardia indicated that kefir significantly reduced the intensity of giardia infection and displayed a protective ef- fect against this infection by ensuring that humoral and cellular immu- nity is stimulated with different mechanisms (Franco et al., 2013).
8.5.8 obesity and Kefir
Intestinal microbiota and an obesogenic diet type are environ- mental factors that are responsible for weight increase and altered energy metabolism. Therefore, modulating the intestinal microbiota is a recommended method for preventing obesity (Kim et al., 2015).
Nonalcoholic fatty liver disease (NAFLD, which causes increases in cardiovascular disease and the resultant mortality rate, is related to overweight or obesity. With altered composition of intestinal micro- biota, evidence shows increased changes related to liver disease. In a study conducted to determine the effect of kefir, a natural and com- plex probiotic, on obesity and liver steatosis, rats consuming a fatty diet were separated into two groups; one group was administered kefir for 12 weeks and the control group was administered milk. The body weight of the group that consumed kefir significantly decreased com- pared to that of the control group, and Lactobacillus/Lactococcus and the total yeast amount was higher, which showed a strong correlation with adiposis and PPARα genetic expression in hepatic tissue. This study showed that kefir regulated the intestinal microbiota and pre- vented obesity and NAFLD by stimulating fatty acid oxidation (Dong- Hyeon et al., 2017). A study conducted to investigate the preventive effect of kefir on adiposis and fat collection on liver tissue in obese rats that consumed a fatty diet indicated that kefir significantly reduced the increase in body weight and prevented fat collection on liver and epididymal fat tissues by inhibiting triaxial glycerol and adipose tissue and fatty acid synthesis. In addition, proinflammatory marker levels decreased in epididymal fat tissues, and expressions of the genes re- lated to adipogenesis and lipogenesis decreased (Choi et al., 2017).
Results of a study that evaluated the effect of kefir peptides on hepatic steatosis caused by high-fructose corn syrup suggested that kefir pep- tides improved the symptoms of NAFLD such as body weight, inflam- mation reactions, and liver lipoidosis. Consumption of high-fructose corn syrup causes leptin resistance, and kefir peptides decrease leptin resistance and heal NAFLD by activating JAK2 signals through JAK2/
STAT3 and JAK2 /AMPK paths (Chen et al., 2016).
In another study, premenopausal women whose ages ranged from 25 to 45 years were assigned to three groups and were followed for 8 weeks.
The first group was administered two portions of low fat milk (control group) daily, the second group consumed four portions of low fat milk (milk group) daily, and the third group consumed two portions of low fat milk and two portions of kefir (kefir group). The body weight, waist circumference, and BMI (body mass index) of those in the kefir and milk group were significantly lower than those of the control group at the end of the eighth week. However, no statistically significant difference was found between the kefir and milk groups in the same study, and kefir caused a similar weight loss compared to milk (Fathi et al., 2016).
8.5.9 its effects on Plasma glucose level
Diabetes mellitus is related to increased morbidity and mortality.
Complications such as nephropathy, retinopathy, and neuropathy may occur if diabetes mellitus is left untreated (Wibowo et al., 2014).
Some studies have indicated that kefir improved insulin resistance and reduced hyperglycemia (Pereira et al., 2016). In one study, glucose tolerance improved in rats that were administered kefir for 8 weeks.
Symptoms such as polydipsia, polyphagia, and polyuria, often seen in diabetes, were reduced with kefir ingestion, and proteinuria and azo- temia were healed, thanks to its antioxidative effect, in rats with type 1 diabetes. Thereby, the progress in renal damage was averted (Punaro et al., 2014). Mature rats with type 2 diabetes were administered kefir (200 mL/day) for 30 days to determine the effect of kefir on their glyce- mic and HbA1c levels; fasting glucose and insulin levels significantly decreased compared with the group that was not administered kefir (Wibowo et al., 2014). In studies conducted with animal models with hypertension, kefiran reduced blood pressure and blood glucose level (Pereira et al., 2016). The antiinflammatory interleukin (IL)-10 level increased while proinflammatory cytokines such as IL-1 and IL-6 were lowered in rats with type 1 diabetes treated with kefir compared to the group that was not administered kefir (Aune et al., 2013). One of the significant characteristics of diabetes is endothelial dysfunction (Pereira et al., 2016). In another study, kefir significantly reduced en- dothelial dysfunction in hypertensive rats (Friques et al., 2015). Kefir improves insulin resistance and reduces HbA1c and fasting glucose levels (Ostadrahimi et al., 2015).
Oxidative stress caused by hyperglycemia contributes to the de- velopment of diabetes complications. Oxidative stress also plays role in the development of chronic inflammation in diabetes patients.
Interleukin-6 (IL-6) and C-reactive protein (CRP) are the systemic in- flammation markers that are related to insulin resistance, type 2 dia- betes, and hyperinsulinemia (Sunarti et al., 2015). A study conducted to determine the comparative effects of kefir made from soybean milk and goat milk on IL-6 and CRP levels in diabetic rats suggested that the plasma glucose level of diabetic rats that consumed goat milk kefir and of rats that consumed both types of kefir significantly decreased.
The same study found that the CRP levels of diabetic rats that were not administered kefir were significantly higher than those of the group that consumed goat milk kefir, and the IL-6 levels of all diabetic rats that were administered kefir were significantly lower than those of the group that did not consume kefir (Sunarti et al., 2015). In yet another study, blood glucose levels of rats that consumed soymilk kefir and goat milk kefir decreased, and pancreatic β cells improved (Nurliyani et al., 2015).
Kefir can relieve hyperglycemia, insulin resistance, and hyperlip- idemia, and it can improve intracellular metabolic imbalance. Studies suggest that kefir can be used as a supplementary treatment for a bet- ter glycemic control in diabetes mellitus (Pereira et al., 2016).
8.5.10 its effects on the gastrointestinal system
Kefir is observed to have important effects on the gastrointestinal system. Kefir prevents the penetration of harmful substances such as food antigens. Fermented dairy products inhibit undesirable mi- croorganisms and assist in the repopulation of beneficial lactic acid microflora in the small intestine (Ahmed et al., 2013). Among the cri- teria for a probiotic bacterium is resistance to the strict demands of gastrointestinal system, such as the presence of pH issues, bile salts, and digestive enzymes. In addition, probiotic bacteria protect against pathogenic bacteria by connecting with intestinal epithelial cells, competing with or replacing them. Milk kefir can temper the pH level in the stomach, and thus it can provide extra time for many bacteria to pass to the upper parts of the small intestine (Farnworth, 2005).
Foods with probiotic substances can alter the intestinal microbiota and provide beneficial effects for the host, either by ensuring that new species enter the gastrointestinal system or by promoting increased growth of beneficial bacteria (Bourrie et al., 2016). In an animal study, kefir consumption increased the number of beneficial bacteria such as lactobacilli and bifidobacteria and reduced the harmful bacteria such as Clostridium perfringens (Hamet et al., 2016). Another study suggested that kefir consumption might relieve the severity of Giardia intestinalis infection in rats (Franco et al., 2013). Clostridium difficile is an anaerobic Gram-positive bacterium that causes problems in the gastrointestinal system, such as diarrhea. With the emergence of antibiotic-resistant strains, the incidence of diarrhea related to Clostridium difficile has increased. A study in rats indicated that ke- fir is protective against enterocolitis caused by Clostridium difficile (Bolla et al., 2013).
In a study on the effect of regular kefir consumption on probiotic bacteria in the human stool, 50 women volunteers (age 18–55 years) consumed kefir (200 mL/day) for 14 days. The amount of Enterococcus faecalis in stools decreased. Because Enterococcus faecalis produces hydroxy radicals, this bacterium may be a source of oxidative stress on the intestinal epithelium. Enterococcus faecalis may also be produced in extracellular superoxide (Forejt et al., 2007). A study on the effect of kefir on the microbiology of gosling feces revealed that kefir that was administered for 5 weeks increased the total population of lacto- bacilli species and decreased the population of Enterobacteriaceae, thus significantly affecting the distribution of the bacterial population.
This study suggested that kefir might affect the population of Candidae by altering the intestinal microflora (Yaman et al., 2006).
The regulatory effect of kefir on intestinal microbiota is related to pathogenic microorganisms and direct interaction with the acid and bacteriocins (Leite et al., 2013a). For 4 weeks, 20 adult patients with functional constipation were administered kefir (500 mL/day), and stool frequency, concentration, and laxative consumption frequen- cies were evaluated. Kefir consumption was found to increase the def- ecation frequency of the patients with functional constipation, to alter the stool concentration, and to reduce the frequency of laxative intake (Turan et al., 2014).
The intestinal epithelial barrier is important for intestinal hemo- stasis: it can prevent the entry of luminal microbial content through the lamina propria. Intestinal barrier function is regulated by intesti- nal microbiota by various mechanisms. Probiotics are recommended in the treatment of diseases related to intestinal inflammation and for the regulation of intestinal barrier function. Lactobacillus kefiranofa- ciens is a heterofermentative bacterium isolated from kefir. A study on the effect of Lb. kefiranofaciens M1 on the intestinal epithelial cells of rats with colitis indicated that Lb. kefiranofaciens M1 strengthened epithelial barrier function, reduced blood buildup score, reduced the formation of proinflammatory cytokines, and increased the antiin- flammatory cytokine IL-10. The study found that Lb. kefiranofaciens M1 has an anticolitis effect and suggested that it could be used as an alternative treatment for intestinal diseases (Chen et al., 2011).
Stomach ulcer affects more than 10% of the world’s population.
Exposure to stress, alcohol, and nonsteroidal antiinflammatory drugs are among the causes of stomach ulcer. In addition, radiation enteritis is a significant health problem caused by the cytotoxic effect of radio- therapy on intestinal mucosa. Response of the stomach to radiotherapy may vary from acute gastritis to ulceration. Radiation generates ROS, which destroys cancer cells. However, normal cells may be damaged by the radiation. The aim in the treatment of stomach ulcer is to inhibit gastric acid secretion, to stop apoptosis, and to stimulate the prolifera- tion of epithelial cells. Certain drugs used in the treatment may nega- tively affect the absorption of certain food elements. Thus, the effect of kefir on stomach ulcer in rats administered a γ beam as an alternative treatment method was examined. That study found that kefir reduced acid secretion and increased mucus secretion; therefore, it showed an antiulcer effect (Fahmy and Ismail, 2015). Kefir also inhibits the over- growth of Helicobacter pylori bacteria that lead to gastric diseases such as ulcer and stomach cancer. Another study indicated that kefir is ben- eficial in the treatment and control of Helicobacter pylori, and also acts as a stimulant on gastric discharge function (Zubillaga et al., 2001).
In another study, 28 Wistar rats were separated into two groups, one
group that consumed kefir for 7 days and the other that did not. The findings of this study indicated that kefir did not increase the amount of gastric mucus or improve the protective characteristic of the mu- cus, but that kefir displayed a positive effect in the rats in which ul- cers were generated using nonsteroid antiinflammatory drugs (Orhan et al., 2012).
8.5.11 Wound Healing
Wound healing consists of a set of actions such as cellular division, cell migration, chemotaxis, and differentiation of many cell types.
Although topical antibiotics are generally used for wound healing, alternative treatments are of interest due to bacterial resistance and side effects of antibiotic overuse. Studies report that probiotics reduce inflammation following lymphocyte and macrophage collection in- stead of wounds, strengthen the immune system, and accelerate the wound-healing process through the antibacterial characteristic of ke- fir polysaccharides that prevent the proliferation of pathogenic bac- teria (Huseini et al., 2012). A study conducted with rats reported that kefir increased collagen collection in the rats that developed corrosive esophagitis and had a positive effect on wound healing (Yasar et al., 2013). Kefir acts to prevent the growth of bacteria and fungus cells, modulates the immune system, and accelerates the progress of wound healing (Bourrie et al., 2016). In another study conducted with rats to evaluate the wound-healing effect of kefir, an infection-based wound that was treated with kefir gel for 7 days shrank rapidly (Rodriguesa et al., 2005).
8.5.12 antiallergic effects
Food allergy is an alarming disease worldwide, and its prevalence is increasing (Nielsen et al., 2014). Eosinophils are the immune system elements that are present in the inflammation area during allergic re- actions; they play an active role in the pathological process that starts with the allergen. For allergy-related diseases such as bronchial asthma and atopic dermatitis, eosinophils are increased in blood and relevant tissue (Köroğlu et al., 2015). One of the main mechanisms of food al- lergy is the increase in the immunoglobulin E (IgE) response due to the imbalance in the T helper cell 1/T helper cell 2 (Th1/Th2) rate (Bourrie et al., 2016). There are studies that indicate that lactic acid bacteria prevent and heal allergic diseases. The mechanism of the antiallergic effect caused by lactic acid bacteria is not completely known, but it is believed that cytokines stimulated by those bacteria play a key role in immunoregulation. Activation of the Th1 response by probiotic lacto- bacillus is accomplished with the assistance of cytokine production.
IL-12 plays a critical role by stimulating the Th1-dominant immune response and altering cellular immunity (Hong et al., 2010). Regular consumption of kefir inhibits IgE and IgG1 responses. Therefore, food allergy may be prevented by altering intestinal microbiota, and muco- sal resistance to gastrointestinal pathogen infection can be improved (Liu et al., 2006). In another study, kefir was found to inhibit ovalbu- min (OVA)-based eosinophilia and mucus hypersecretion on the lung tissue in rats that developed asthma. IgE, IL-4, and IL-13 levels of the rats that were administered kefir were significantly low, and this was reported to be related to the Th2 response that was responsible for al- lergic reactions (Lee et al., 2007). In another study conducted on this topic, Lactobacillus (Lb.) kefiranofaciens M1 inhibits IgE production as a response to in vivo OVA (Hong et al., 2010). Kefir can play a signif- icant role in reducing the allergic response in food allergies thanks to its immunomodulatory effects (Nielsen et al., 2014).
8.5.13 Kefir’s effects on Bones
Inadequate calcium intake worsens the loss of bone mass and in- creases osteoporosis risk in premenopausal women. In cases of bone mass loss that result from the decrease in intestinal calcium absorp- tion and postmenopausal estrogen insufficiency, the consumption of calcium should be increased. Food elements such as vitamins, pro- teins, and amino acids alter calcium absorption and promote bone formation, thus contributing to the prevention of osteoporosis. Dairy products are good sources of calcium, and they increase bone forma- tion, prevent bone loss, and decrease bone resorption (Tu et al., 2015).
Kefir increases bone mineralization and formation and reduces bone destruction: it contains calcium, protein, and probiotic elements.
Probiotics in kefir help the intestinal microbiota and immune modu- lation, reduce TNF-α in the intestines and bones, and decrease the rate of bone loss. With its protein components, kefir boosts the increase of insulin-like growth factor (IGF)-I and thereby bone formation. Kefir also alters intestinal microbiota and provides increased bone miner- alization as the intestinal permeability is modified and calcium ab- sorption is increased. In addition, increases in the calcium absorption rate reduce the parathyroid (PTH) level and bone resorption (Rizzoli and Biver, 2017). A 6-month interventional study conducted with 40 patients who had been diagnosed with osteoporosis compared the ef- fect of kefir enriched with calcium bicarbonate (CaCO3) on bone me- tabolism with the effect of calcium carbonate. It was found that the bone mineral density (BMD) of the group that was administered kefir improved significantly in the sixth month, and serum osteocalcin level turned from negative to positive. In addition, the serum PTH level in- creased in the group that was administered kefir and decreased in the
nonkefir group; it was concluded that ingested kefir was significantly related to the changes in BMD among the osteoporotic patients (Tu et al., 2015). A study conducted using rat models on which ovariec- tomy had been performed examined the effect of kefir on osteoporo- sis; the results suggested that kefir increased BMD, and the increase was dose-dependent. In addition, kefir increased intracellular calcium uptake; thus, it can be effective in treating or preventing osteoporosis (Chen et al., 2015).
8.6 Water Kefir
Water kefir is a fermented beverage prepared with a sucrose solu- tion containing different dried fruits and fresh fruits. During the prepa- ration process, kefir particles are added to the solution containing 8%
sucrose, dried fruits, and lemon slices. This mixture is kept at room temperature for 1 or 2 days for fermentation. The result is a cloudy, acidic, high-sugar, and slightly alcoholic beverage. The origin of water kefir is unknown. However, it is thought that the origin is related to the particles called “gingery plants”, which British soldiers brought when they returned from Crimean War in 1855, or possibly to Mexican cac- tus. These particles were named sugary kefir particles later to show that they are different from the particles that arise from fermenting milk (Gulitz et al., 2011). Water kefir contains a substrate, approxi- mately 80% of the total volume, at the beginning of the fermentation process, and this substrate consists of minerals including 90% sucrose, 6% reduced sugar, and 1.5% iron, calcium, magnesium, potassium, phosphorus, zinc, and copper. The major end products of fermenta- tion are ethanol, lactic acid, mannitol, acetic acid, glycerol, and other organic acids (Fiorda et al., 2017).
The microbiotic content of water kefir is generally stable with different lactic acid bacteria, acetic acid bacteria, and yeasts. Water kefir particles contain dextran, a glucose polymer with an α 1–6 link- age structure (Gulitz et al., 2011). Although milk kefir and water kefir particles appear structurally similar, the density and composition of microbial species and the concentration of the end product may vary by the presence of carbon and energy sources that are necessary for fermentation. Yeasts are common in both milk kefir and water kefir. In addition, water kefir includes yeast genera such as Hanseniaspora and Lachancea, which have a strong capacity for fermentation. The pres- ence of these yeasts in water kefir may contribute to the increase of its sensory quality. Regarding the bacterial composition, Lactobacillus is the more dominant genus in both milk and water kefir. In addition, the Bifidobacterium genus was detected in water kefir (Gulitz et al., 2013; Laureys et al., 2016). Bifidobacterium species contribute to the synthesis of vitamin K and complex B vitamins in the intestines.
Bifidobacteria increase the concentration of organisms related to a decreased stool concentration of potential pathogenic bacteria, and reduce the number of carcinogenic components in the digestive sys- tem (Fiorda et al., 2017).
Water kefir has different effects on human health. It is thought to be suitable for individuals who are vegan and/or vegetarian and have lac- tose intolerance, although this has yet to be proven. Probiotic micro- organisms isolated from water kefir have certain characteristics such as colonizing in the gastric mucosa and competing with pathogens. In addition, they are antiinflammatory, antimicrobial, and antioxidant, and they heal wounds (Fiorda et al., 2017). Water kefir inhibits certain patho- genic bacteria such as S. pyogenes, S. salivarius, S. aureus, P. aeruginosa, S. typhimurium, E. coli, L. monocytogenes, and C. albicans. In addition, water kefir’s probiotic organisms have beneficial effects on the acute in- flammatory response. This effect is thought to arise from serotonin re- ceptor and arachidonic acid pathways (Thomaz-Soccol and Schneedorf, 2012). In a study conducted to determine the antigranulomatous effect of water kefir and milk kefir, it was found that inhibition-related effects of water kefir and milk kefir are similar (Rodrigues et al., 2005). Rats were treated with water kefir for 7 days to evaluate the immune activity of neu- trophils, and the number of general neutrophil activities was found to decrease (Thomaz-Soccol and Schneedorf, 2012).
The major reason for deaths due to breast cancer is metastasis to crucial body organs. Rats that were injected with 4TI carcinogenic cells to determine the antimetastatic and antiangiogenic effects of wa- ter kefir, produced from kefir particles, on 4TI breast cancer cells were treated with water kefir for 28 days in Malaysia. This study indicated that water kefir significantly reduced the size and weight of tumors, and it increased the number of helper T cells by five times and cyto- toxic T cells by seven times. This study indicated that water kefir has antiinflammatory, antimetastatic, and antiangiogenesis effects; thus, it can be used in cancer treatment (Zamberi et al., 2016).
8.7 Summary
Kefir is a complex probiotic that contains combinations of bacteria and fungi. Kefir is obtained from the fermentation of traditional and commercial semiskimmed or skimmed pasteurized milk types (goat, cow, sheep, and camel) with kefir particles. The differences, types, and size of the population in the microbiota of kefir particles, micro- biologic profile of the milk, and physical or geographical differences cause difference in the color, taste, smell, and chemical or microbial composition of the end product.
The antiinflammatory characteristic of kefir arises from its direct effect on microbiota or indirect bioactive compositions that emerge
during the fermentation process. Bioactive peptides that are produced by the microbiota of kefir during fermentation activate macrophages, boost the formation of nitric oxide and cytokines, and stimulate the secretion of IgG and IgA by B lymphocytes in the intestinal lumen.
Organisms in kefir form many antimicrobials such as lactic acid, acetic acid, carbon dioxide, hydrogen peroxide, ethanol, diacetyl, and bac- teriocins. Kefir displays its antibacterial effect thanks to these organic acids, hydrogen peroxide, carbon dioxide, bacteriocin, and acetalde- hyde. The antimicrobial characteristics of kefir may be beneficial for wound healing: the β-galactosidase enzyme is naturally present in ke- fir particles. In addition, the lactose content in kefir decreases during fermentation and thus kefir becomes suitable for persons who are lactose intolerant. Studies indicate that kefir has an anticarcinogenic effect arising from its bioactive components such as peptides, poly- saccharides, and sphingolipids. Proteolysis of milk casein takes place during the fermentation of kefir. It is believed that the peptidic frac- tions stimulate the growth of kefir bacteria and regulate the immune system. Kefir is a fermented beverage that is suitable for healthy or ill adults and children. However, more studies should be conducted to analyze the medicinal and functional characteristics of kefir against disease.
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