¹Department of Pharmacy, School of Medical and Allied Sciences Galgotias University, Greater Noida, Uttar Pradesh, India

²School of Pharmacy, Sharda University, Greater Noida, Uttar Pradesh, India

³B.S. College of Pharmcy, Fatehullapur, Ghaziapur, Uttar Pradesh, India

⁴Saraswati College of Pharmacy, Pilkhua, Hapur, Uttar Pradesh, India

⁵Department of Pharmacy, Lloyd Institute of Management and Technology, Greater Noida, Uttar Pradesh, India.

Corresponding author email: heema.arya@sharda.ac.in

Article Publishing History

INTRODUCTION

Probiotics improve the digestion of lactose, especially for the lactose-intolerant individual. It reduces cholesterol levels and blood pressure. It improves the absorption of minerals, especially calcium from the body (Verschuere et al., 2000). It decreases the dental-caries caused by microbes present in the mouth. Probiotics used to cure vaginal yeast infections and in urinary tract infections treatment. It manages the signs and symptoms of irritable bowel syndrome. Reduces the amount of cancer causing substances in the intestine. Reduce the development of allergy in children and also reduces the infections and inflammation (Kerry et al., 2018, Verschuere et al., 2000; Kerry et al., 2018).

Probiotics provide bile acid tolerance which is difficult to maintain during oral administration. Adherence to epithelial and mucosal surfaces is a crucial factor for successful immune modulation, competitive exclusion of pathogens and pathogen adherence and colonization prevention. It has antimicrobial activity against pathogenic bacteria and also act as bile salt hydrolase (Ziemer and Gibson,1998; Kerry et al., 2018).

Types of Probiotics: Different types of probiotics are described below:

1. Lactobacillus: Lactobacilli have more than 50 species. They are found naturally in the urinary, genital and digestive systems. Fermented food like yogurt is used as dietary supplements. Lactobacillus has been used to treat and prevent a wide variety of diseases and conditions. Different Lactobacilli species are found in foods supplements such as Lactobacillus acidophilus, Lactobacillus bulgaricus, L.acidophilus DDS-1, Lactobacillus rhamnosus GG, Lactobacillus reuteri, Lactobacillus salivarius, Lactobacillus plantarium, Lactobacillus johnsonii, Lactobacillus casei etc. Lactobacillus can prevent and treat bacterial vaginosis, yeast infections, urinary tract infection, antibiotic-related diarrhoea, irritable bowel syndrome, travelers diarrhoea, diarrhoea resulted from Clostridium difficile, skin disorders, treating lactose intolerance and respiratory infections prevention (Ziemer and Gibson, 1998; Amara and Shibl, 2015).

 

2 Bifidobacteria: Bifidobacteria have more than 25 species. They are used to make up healthy bacteria in the colon. It exists in the intestinal tract of breastfed infants from the day of birth. Bifidobacteria species are used as probiotics such as Bifidobacterium bifidum, Bifidobacterium longum, Bifidobacterium lactis, Bifidobacterium breve, Bifidobacterium thermophilum, Bifidobacterium infants and Bifidobacterium pseudolongum. Bifidobacteria help to increase glucose tolerance and blood lipids levels. Bifidobacteria improve symptoms of the IBS such as pain, discomfort, bloating distension, disorders of digestion (Amara and Shibl, 2015).

3. Saccharomyces boulardii: This bacteria is the only yeast probiotic called as S. boulardii. It may prevent and treat traveler’s diarrhoea and diarrhoea associated with the use of antibiotics. It has been also used to prevent C. difficile reoccurrence which helps to treat acne and reduce side effects of H. pylori treatment (Kerry et al., 2018,; Amara and Shibl, 2015.

4. Streptococcus thermophilus: It produces a large amount of the lactase enzyme and helps to prevent the intolerance of lactose.

5. Enterococcus faecium: It is commonly present in both the human and animal intestinal tract.

6. Leuconostoc: It is used in food processing from a very earlier time. The foods containing metabolites of microorganisms, live bacteria and dead bacteria are ingested from a long time (Amara and Shibl, 2015).

Figure 1: Schmeatic diagram to show best probiotics food

Different types of probiotics are shown in figure 2.

Probiotics In Helicobacter pylori Infections: H. Pylori induces multiple gastrointestinal diseases like chronic gastritis and peptic ulcer. The latest treatment choices are antibiotics and proton pump inhibitors. Probiotics have been used to supplement infection control by using different Lactobacillus species which is demonstrated in both in vitro and in vivo studies. From in vitro studies, it was suggested that direct antimicrobial activity of Lactobacillus species occurs by competition with H. pylori, thereby demonstrating the clinical progress in patients treated with probiotics (Markowiak and Slizewska, 2018).

Figure 2: Schematic diagram of different types of probiotics

However, the results are positive, yet probiotics can not be proposed as a valid substitute for H. Pylori infections standard treatment. Helicobacter pylori is a bacterium in small curved to spiral rod shape. It is strongly associated with duodenal peptic ulceration and used as the main etiologic agent for chronic gastritis, gastric cancer and other gastric malignancies (Tripathi and Giri, 2014). Today, the therapy based on a combination of antibiotics and proton pump inhibitors are used to kill this bacterium. Probiotics tend to have a direct antimicrobial effect which was demonstrated through in vitro studies, competing with H. pylori, adherence inhibition, metabolites production and antimicrobial molecules. (Markowiak and Slizewska, 2018, Tripathi and Giri, 2014).

In a study, 60 participants were treated with triple antibiotic therapy on days 1-7 and Lactobacillus GG on days 1-14 in a double blind, randomized, placebo-controlled trial. Probiotics considerably improved the symptoms of taste disturbance, nausea and diarrhoea. However, epigastric pain during eradication treatment did not significantly improve. The eradication rates between the groups did not differ significantly (83.3% vs 80%) (Tripathi and Giri, 2014; Markowiak and Slizewska, 2018).

In another placebo-controlled, randomized, double blind trial the asymptomatic 85 patients of H. pylori were randomized to receive treatment from days 1-7 with placebo from days 1-14. Probiotics show significantly improved symptoms during treatment of diarrhoea and taste disturbance; but epigastric pain and nausea did not improve significantly during H. pylori treatment (Granato et al. 2010). During the study all the differences between the probiotics and placebo were noted. None of the probiotics has been better than another. Eradication rates among the 4 groups that received probiotics were not significantly different. A randomized double-blind placebo-control study was conducted on 47 patients using a milk based fruit drink containing Propioni bacterium, Lactobacillus GG, Bifidobacterium, or placebo from day 1-28 and triple antibiotic therapy from days 1-7 (Granato et al., 2010).

Probiotics did not improve symptoms significantly, including taste disturbance, nausea, epigastric pain and diarrhoea (Ziemer and Gibson, 1998,; Granato et al., 2010). Recently a meta-analysis showed that supplementation with S. boulardii significantly raised the eradication rate and reduced the overall risk for H. pylori related adverse reactions, particularly in diarrheoa. However, the products used in such trials are not usually marketed in the US, making it difficult to support evidence related to probiotic. Although a specific strain of Lactobacillus supported by the US may not be available in the market, because it may not be fair to extrapolate the results of strain to other types of Lactobacillus so the product selections are limited (Butel, 2014).

Probiotics In Irritable Bowel Disease: Gastrointestinal problem includes irritable bowel syndrome (IBS), abdominal pain and excessive flatulence. Motility disorders and psychological mechanisms have been suggested to differentiate the intestinal microflora in people with IBS and with healthy peoples. In comparison with healthy people, these patients have low numbers of Llactobacilli, Bbifidobacteria and higher numbers of facultative microbes. Probiotics are used as therapy but the results are unclear. A preventive strategy may have more benefit for Llacto bacillus than when it is used in the IBS treatment, although this has not been confirmed. (Amara and Shibl, 2015).

The role of intestinal bacteria in the IBS pathogenesis has been suggested by physiological, epidemiological and clinical trials. Some earlier studies indicate that gastroenteritis is the main cause of IBS (Butel, 2014)[14]. A cohort study in Canada, an epidemic of gastroenteritis showed an increased IBS patient in 2 years, which lasted for 8 years. In another study, the incidence of gastroenteritis was associated with approximately a four-fold rise in the probability of developing IBS in the previous 2 years. Physiological research on animals and humans demonstrated a profound impact of alterations in the intestinal microbiota composition of the normal and IBS patients intestine (Amara and Shibl, 2015). The developing IBS increases the risk of dysbiosis, gastroenteritis and increases the production of luminous gas and immune activation suggests that the gastrointestinal microbiota may be a therapeutic target for IBS (Butel, 2014; Amara and Shibl, 2015, Butel, 2014).

While numerous probiotics efficacy Randomized Clinical Trials have been assessed with IBS patients, they often suffer from severe methodological flaws. Brenner and colleagues reported in a recent systematic review that 16 RCTs were assessed as effective probiotics in the treatment of IBS, Bifidobacterium infants 35624 was the only probiotic that offered substantial improvements in IBS symptoms. VSL#3 has demonstrated a greater improvement in abdominal pain and bloating symptoms globally. A randomized cross-over trials was done with 59 children having IBS. Some meta-analysis indicates that probiotics have a more beneficial effect on abdominal pain and flatulence.  Bifidio bacterium is available on the market in combination with Align capsules or other probiotic organisms as OWP probiotic capsules, and VSL#3 packets for the treatment of IBS. More evidence is needed before IBS is used as probiotics for control symptoms (Rivera-Espinoza and Gallardo-Navarro, 2010).

Probiotics and Bacterial Translocations: Many studies have been shown that patients who are unable to feed enternally after severe gastrointestinal surgery or liver transplantation also have a high risk of septicemia from the intestinal tract triggered by bacterial organisms. A study describes various ways in which probiotics can decrease bacterial translocation. It seems possible to eliminate postoperative infections by altering the luminal bacterial milieu. The research results are promising but need confirmation in larger prospective studies. In mesenteric lymph nodes (MLN), the detection of viable bacteria represents bacterial translocation in the intestine lumen. (Millette et al., 2013). Each rats lymph nodes were aseptically removed from the ileocaecal and left colonic regions and dissected (Millette et al., 2013).

Nodes were then homogenized for the cultivation of aerobic and anaerobic bacteria in 1 ml of sterile phosphate buffer saline or thioglycollate broth respectively. At 37°C, a 0.1 ml aliquot of each homogeneous was placed on blood agar and incubated and the number of colonies was counted on all plates. Bacterial translocation data are defined as medians and ranges of the total colony forming unit (CFU) (both aerobic and anaerobic) will be calculated from the cultured plate after 48 hours of incubation from MLN of each rat (Cousin et al., 2012; Millette et al., 2013, Cousin et al., 2012).

Probiotics and Safety: Over the last few decades the use of probiotics has increased, especially in dairy products. The studies focus on infection risk, toxicity, deleterious metabolic activity and antibiotic resistance with increasing probiotic strain in dairy products (Ozyurt and Otles, 2014). In safety assessment, children and infants are especially found to be vulnerable at a period when the intestinal environment and the immune system are under development. However numerous studies have not shown any adverse results even on preterm infants. It seems like most people do not suffer from probiotics side effects or have just mild gastrointestinal side effects including gas. But there have been several case reports of serious adverse effects (Kent and Doherty, 2014).

A review on probiotics safety suggested that Lactobacillus rhamnosus GG was widely studied for a variety of conditions in clinical trials and found to be generally safe. Nevertheless, a recent review of Lactobacillus and Bifidobacterium noted the long-term, cumulative effects of probiotics use, especially in children and also indicates the evidence that probiotics should not be used in patients with a critical illness (Saxelin et al., 2010). Similarly, a 2011 Agency for Healthcare Research and Quality Assessment on the safety of the probiotic, partly funded by National Center for Complementary Alternative Medicine (NCCAM), concluded that the current evidence does not suggest a widespread risk for probiotic related side effects. However, safety data, especially long-term protection are limited and the risk of serious side effects in people may be greater with underlying health conditions (Garanto et al., 2010; Saxelin et al., 2010;19,20 Kent and Doherty, 2014).

Eukaryotic Probiotics: Eukaryotic microorganisms are very useful as probiotics for animal health. There are several eukaryotes grade of food/feed, like as algae (e.g. Spirulina, Chlorella species), fungi (e.g. Penicillium, Aspergillus species), yeasts (e.g. Candida, Saccharomyces, Pichia, Kluyveromyces, Torulopsis species), which are being consumed by human and animals throughout the world since a very long time. These organisms are mostly used as single cell protein and as food starters components. However, certain eukaryotes are found to be executing probiotics like beneficial effects in the host when supplemented in living conditions through diet (Hennequin et al., 2000) (Hirimuthugoda, Chi and Wu, 2007).

Therefore, the development of new candidate species beyond prokaryotic origin is believed to be a very crucial event in the field of probiotics. Significant interest in eukaryotic probiotics is growing nowadays and in most cases their efficacy and usefulness have been proven by strong scientific evidence. Most of the eukaryotic probiotics used in human and animal practices belong to the dominant group of fungi, yeasts and mould. Pichia, Candida, Saccharomyces, Yarrowia, Metschnikowia, Isaatchenkia, Debaryomyces, Aspergillus and Kluyveromyces are common examples of eukaryotic microorganisms with probiotic properties (Holubarova, Muller and Svoboda, 2000). From 1,550 BC, yeast has historically been used for fermentation purposes. Nowadays, yeasts are a part of dietary supplements and healthy food realms because of their proven beneficial probiotic effects. Saccharomyces genus of yeast has commonly used probiotics in humans and animals worldwide (Hottiger, Boller and Wiemken, 1987; Holubarova, Muller and Svoboda, 2000).

Mode of Action of Probiotics: Several studies have demonstrated several types of probiotic action in the aquatic environment. Selected strains were determined to produce digestive enzymes, thus facilitating the utilization and digestion of the feed. The enzymatic properties of intestinal anaerobic bacteria isolated from three species of fish, showing the potential role as a probiotic. In the research, the addition of the two intestinal fish Bacillus spp. was done. Increased performance as assessed by several factors including growth, feed conversion and protein efficiency ratio (Gomez-Gil, Rogue and Velasco-Blanco, 2002). The bacteria attributed the result to the production of the extracellular cellulolytic and amylolytic enzymes. While competition has been widely suggested as a mode of action for adhesion sites, there is little evidence in the literature to prove this fact. Studies report adhesion of certain bacteria to in vitro intestinal mucus and the attachment ability of potential probiotics seen in vitro can not be assumed to demonstrate the real in vivo effect (Gomez-Gil, Rogue and Velasco-Blanco, 2002).

Additionally, studies have shown the ability of some bacteria to adhere with in vitro intestinal mucus they have failed to assess a competitive exclusion effect. More recently, it has been shown that five probiotics versus two pathogens on fish intestinal mucus exhibited a competitive exclusion effect. The presence of one of the probiotics on the mucus was found to inhibit the attachment of one of the tested pathogens. Interestingly, pre-colonization with the other probiotics prompted the two pathogens to attach themselves. However, the general trend of their research has shown that the pathogen was displaced after treatment with probiotics (Holubarova, Muller and Svoboda, 2000,; Gomez-Gil, Rogue and Velasco-Blanco, 2002).

Although not directly related to attachment competition, it was shown that two seaweed-associated Bacillus spp. produced antibiotic substances. It was dependent on bacteria forming biofilms. This study highlighted a factor i.e. surface attachment, that could be essential for some bacteria to be successful probiotics. This observation concurred with the definition of a probiotic, i.e. the colonization requirement for GIT. (Rogue and Velasco-Blanco, 2002).

It was suggested that the competitive exclusion mechanism for attachment sites could be given a distinct advantage through the addition of probiotic bacteria during the larviculture initial egg fertilization steps, thus “getting in there first”. This concept was not supported because when these bacteria were administered at hatching and two days after hatching, no difference was observed between the concentrations of two bacteria in the gut of turbot larvae. Several studies have attributed a probiotic effect to an energy source competition. Artemia sp. was found beneficial for growth and survival.

It was pre-exposed to nine bacterial strain before challenging with V. proteolytic. It was concluded that the extracellular products do not cause any effect, but the live bacterial cell was required. Although not specifically tested, they hypothesized that the protective effect was probably the result of competition for energy sources and sites of adhesion. Competition for iron has been reported as an important factor in marine bacteria. Iron is required for the growth of most of the bacteria but is generally limited in the animal tissues and body fluids and the insoluble ferric Fe³⁺ type iron-binding agents, siderophores, enable iron acquisition suitable for microbial growth (Gram et al., 1999).

Siderophore production is a noted mechanism of virulence in some pathogens equally, a siderophore producing probiotic could deprive potential pathogens of iron under iron limiting conditions. This was shown by a supernatant culture of Pseudomonas fluoresces, grown under limited conditions of iron, inhibited V. anguillarum growth, while the supernatant from iron-available cultures did not inhibit the growth (Gram et al., 2001). It was found that the addition of Bifidobacterium thermophilum derived peptidoglycan increased significantly their survival when they were challenged with V. penaeicida. It was attributed that an immune stimulatory effect, as the phagocytic activity of shrimp granulocytes was significantly higher in the treated shrimp compared with those of the control animals. Research differentiated slightly to approach towards immune-stimulating probiotic (Gullian, Thompson and Rodriguez, 2004). Instead of analysing bacterial derivatives such as glycans or lipopolysaccharides, they tested live Vibrio sp. (P62) for immune stimulation and Bacillus sp. (P64) and V. alginolyticus used as a positive control. They concluded the immune stimulants activity of  P64 and V. alginolyticus (Gram et al., 2001; Gullian, Thompson and Rodriguez, 2004).

Probiotic Products: The most popular approach to consume probiotic cells are through food products. The global market for functional foods and beverages has grown from $33 billion in 2000 to $176.7 billion in 2013, representing 5% of the food market as a whole. Probiotic foods are comprised between 60%-70% of the total functional food market. Probiotic microorganisms are typically available as dried or deep-freeze culture concentrates to be added to a food matrix. Lactic acid bacteria of the genera Lactobacillus and Bifidobacterium, are the most common genera and species, as they are widely recognized as safe (Hagi et al., 2004,; Granato et al., 2020).

The species Lactobacillus and Bifidobacterium are also predominate in the human intestine (Bifidobacterium in the large intestine and Lactobacillus in the small intestine). However, bacterial species of the genera Lactococcus, Enterococcus and Propionibacterium, yeasts (e.g. Saccharomyces boulardii and Saccharomyces cerevisiae) and filamentous fungi (e.g. Aspergillus oryzae) are also used as probiotics due to their beneficial effects on health (Satkori, 2019,; Min. et al[31,32]., 2019).

Also, some people suggest that multispecies supplementation of dairy probiotic products may have a more specifically targeted function in the human food tract. Maintaining the viability of probiotic cells during food-processing and gastro-intestinal transit is important for microorganisms to reach adequately the intended site of action (108 cells/gram). (Tarkhani et al., 2020, Barbosa et al., 2011). Due to passage through the low pH environment of the stomach and high bile salt conditions in the intestine, there is a significant loss of viable cells following the ingestion of a probiotic (Barbosa et al., 2011; Tarkhani et al., 2020).

One possible solution for this problem is microencapsulation. Encapsulation is a mechanical or physicochemical process that traps a material that is  potentially sensitive and provides a protective barrier between it and the external conditions. The spray-drying, emulsion and extrusion techniques are well known methods of encapsulation for the processing of probiotics microcapsules (Taskin, 2020). The probiotic effect and survival are strain dependent, therefore it must be perfectly identified and characterized (phenotypic and genotypic identification). Lactobacilli are generally stronger than Bifidobacteria, in terms of robustness of probiotic species, more resistant to low pH and have a greater tolerance to milk and other food substrates. Probiotic products can be classified as dairy probiotic products and non-dairy probiotic products depending on the matrix that carries the probiotic bacteria. Dairy beverages are produced from milk or its derivatives, with or without the addition of other ingredients in which the milk base represents at least 51% v/v of the formulation and can be fermented using yogurt cultures (Taskin, 2020, Guimaraes et al., 2019; Taskin, 2020).

Fermented milks, ice cream, different kinds of cheese, milk powder and baby food, whey-based beverages, frozen dairy desserts, buttermilk, sour cream, normal and flavored liquid milk are the most common dairy probiotic products. Milk and dairy products are abundant minerals sources which play a variety of roles in the human body. However, becuae of the high content of saturated fatty acids the availability of minerals from cheeses and cheese-like products is lower than that from other dairy products (Saxelin et al., 2010). Alejewicz and Cichosz have determined the effect of the probiotic culture of Lactobacillus rhamnosus HN001 on the increase of magnesium, calcium, phosphorus, zinc and potassium in cheese. The addition of Lactobacillus rhamnosus HN001 increases the availability of divalent metal cations. Also, other technologies and methodologies can be applied to existing probiotic dairy products (Taskin, 2020).

Kent and Doherty (2014) used an isotherm differential scanning calorimetry method to identify the probiotic microbes in probiotic products (Kent and Doherty, 2014). The products were developed and now commercial in Hungry. Products are Probiotic kefir (Symbiofir), probiotic sour cream, probiotic butter cream, poultry meat products supplemented with calcium and bakery products complement with calcium. Demonstrated that the optimal concentration of constituents such as whey in probiotic dairy beverages could be calculated by using mathematical models such as survival analysis, minimal significant difference and mean global acceptability. Because of the high prevalence of lactose intolerance, different non-dairy probiotic products such as vegetarian-based products, fruit juices, cereal-based products, oat-based desserts, soya-based products, breakfast cereals, confectionery products and baby foods have been developed in recent years (Saxelin et al., 2010;, Gonzalez-Sanchez, 2010; Kent and Doherty, 2014).

Technological developments have made it possible to alter certain structural characteristics of fruit and vegetable matrices by modification of food components in a controlled way. It could make them perfect substrates for the probiotics culture. Cereal grains are one of the most essential sources of carbohydrates, protein, vitamins, fiber and minerals; Lactobacillus strains are fastidious microorganisms that require these sources for growth. Moreover, cereals can serve as prebiotics because they can be used as sources of non-digestible carbohydrates, encouraging the growth of the colon’s Lactobacilli and Bifidobacteria (Matias et al., 2014). Another good raw material to be used as an alternative for the nondairy probiotic carrier is soy, which has some sugars and amino acids in its composition that are used as substrates by lactic acid bacteria to produce aroma compounds. However, soy intake is limited due to its undesirable beany flavor and the presence of oligosaccharides frequently contributing to flatulence and discomfort in the stomach (Matias et al., 2014).

One way to improve the sensory consistency of soymilk and also to mask undesirable compounds is by fermenting  the lactic acid which can be combined with supplemental glucose, sucrose and lactose. Bakery products like bread are stapled foods composed of many main components (complex carbohydrates, insoluble dietary fiber, lipids, proteins, vitamins and minerals) in varying amounts and with varying physical interactions and structures. Cespedes et al. (2013) Soukoulis et al. developed probiotic bread with addition of the bacteria Lactobacillus rhamnosus GG, using air dried probiotic edible films. Meat can be also provide another source of probiotic products. The buffering capacity of meat may be attributable to an elevated pH of the microenvironment for the living of bacteria on its surface. It is important to continue the research into new non-dairy probiotic products that could have a wide market because of the high prevalence of lactose intolerance and vegetarianism (Cespedes et al., 2013).

CONCLUSION

It can be concluded from the literature survey that probiotics play a vital role in the management of the health of human beings. Proper concentration and species of probiotics are necessary for the maintenance of the immunity of the organism. Probiotics are used in the food supplements which increase the nutritional value of the food which is beneficial for human health. Probiotic microorganisms are available as culture concentrates in dried or deep-freeze form which is added to a food matrix and marketed as a food product. The main products of probiotics developed in recent years are vegetarian-based, cereal-based products, fruit juices, soya-based products, oat-based desserts, confectionery products, breakfast cereals and baby foods. The probiotics are mainly used to maintain the level of good bacteria inside the gastrointestinal tract mainly in the intestine. It helps to decrease the chances of disease related to the gastrointestinal tract. It also proves their activity in the treatment of the various diseases related to humans. The manuscript describes the function, advantages, mode of action and marketed products of probiotics and their role in human health management.

ACKNOWLEDGEMENTS

Authors are highly thankful to the Department of Pharmacy, School of Medical and Allied Sciences Galgotias University to provide library facilities for the literature survey. This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.

Conflict of Interests: Authors have no conflict of in interests.

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Rivera-Espinoza, Y., Gallardo-Navarro, Y. (2010) ‘Non-dairy probiotic products’, Food Microbiology, 27, pp. 1-11.

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Satokari, R. (2019) ‘Modulation of Gut Microbiota for Health by Current and Next-Generation Probiotics’, Nutrients, 11(8), pp. 1-4.

Saxelin, M., Tynkkynen, S., Salusjärvi, T., Kajander, K., Myllyluoma, E., Mattila-Sandholm, T., Korpela, R. (2010) ‘Developing a Multispecies Probiotic Combination’, International Journal of Probiotics Prebiotics, 5, pp. 169-181.

Tarkhani, R., Imani, A., Hoseinifar, S.H., Ashayerizadeh, O., Moghanlou, K.S., Manaffar, R., Van Doan, H., Reverter, M. (2020) ‘Comparative study of host-associated and commercial probiotic effects on serum and mucosal immune parameters, intestinal microbiota, digestive enzymes activity and growth performance of roach (Rutilus rutilus caspicus) fingerlings’, Fish Shellfish Immunology, 98, pp. 661-669.

Taskın, B. (2020) ‘Evaluation of the Antimicrobial Effect of Kefiran Extract against Some Plant Pathogenic Bacteria’, Turkish Journal of Agriculture-Food Science and Technology, 8(4), pp. 889-894.

Tripathi, M.K., Giri, S.K. (2014) ‘Probiotic functional foods: Survival of probiotics during processing and storage’, Journal of Functional Foods, 9, pp. 225–241.

Verschuere, L., Heang, H., Criel, G., Sorgeloos, P., Verstraete, W. (2000) ‘Selected bacterial strains protect Artemia spp. from the pathogenic effects of Vibrio proteolyticus CW8T2’, Applied and Environmental Microbiology, 66(3), pp. 1139–1146.

Ziemer, C.Z., Gibson, G.R. (1998) ‘An overview of probiotics, prebiotics and synbiotics in the functional food concept: perspectives and future strategies’, International Dairy Journal, 8(5), pp. 473–479.