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Prebiotics & probiotics in clinical practice: A primer- Dr. Manish Bhatnagar

M3 India Newsdesk Jun 18, 2021

Probiotics and prebiotics help and heal the body by building and maintaining a healthy group of bacteria and other microorganisms that assist in supporting the gut and aids digestion. This article highlights its functioning and its effect on the human body.


Probiotics

The word “probiotic” (origins: Latin pro meaning “for” and Greek bios meaning “life”) was first used in 1954 to indicate substances that were required for a healthy life. Out of a number of definitions, the most widely used and accepted definition is that projected by a joint FAO/WHO team (FAO/WHO, 2001): “Live microorganisms which, when administered in adequate amounts, confer a health benefit on the host."

At the start of the twentieth century, Russian Nobel Prize winner, Elie Metchnikoff was the first to conceptualise 'probiotics'. He stated: “The dependence of the intestinal microbes on the food makes it possible to adopt measures to modify the flora in our bodies and to replace the harmful microbes by useful microbes” and “systematic investigations should be made on the relation of gut microbes to precocious old age, and on the influence of diets which prevent intestinal decay in prolonging life and maintain the forces of the body.”

A French paediatrician, Henry Tissier was doing research work on young children with diarrhoea. He found that their stools contained fewer unusual Y-shaped (“bifid”) bacteria than did stools from their healthy peers and suggested that patients with diarrhoea could be treated with these “bifid” bacteria to help re-establish a healthy gut microbiota. Until recently, high-value systematic research supporting the supposed benefits of probiotics was limited, partly because the complexity of the gut ecosystem was largely underestimated. In the last three decades, research has progressed and, with the application of molecular techniques, major advances have been made in the classification of specific probiotics as well as in our acceptance of their mechanisms of action and health effects.

In the early thirties, in Japan, Minoru Shirota developed a fermented milk product called Yakult (probiotic yogurt-like product made by fermenting milk with Lactobacillus casei shirota). The term Probiotic was coined in 1965 by Lilly and Stillwell.

Probiotics are live and viable nonpathogenic microorganisms (lactic acid bacteria) in foods that can exert a positive influence on the host’s health and modulate the GI tract. [1] The theory is those live microorganisms within foods or in the form of a supplement improve the microbial balance of the intestinal tract. These are all gram-positive, facultative bacteria that are normal inhabitants of the human colon and constitute a predominant part of the anaerobic flora. Fermented milk products such as yoghurt are the most familiar probiotic products. For use in foods, probiotic microorganisms should not only be capable of surviving passage through the digestive tract but also have the capability to proliferate in the gut. [2]

Lactic acid bacteria (LAB) is the most important group of microorganisms commercially used as starter cultures for the manufacture of dairy-based probiotic foods. Strains of the genera Lactobacillus, Bifidobacterium, and Propionibacterium are the most widely used and commonly studied probiotic bacteria. LAB satisfy the criteria that have to be met by the organisms to be selected as probiotics like resistance to the enzymes in the oral cavity, survival through the GI tract, arrival at the site of action in a viable physiological state and adherence to the host cell surface.


Types of probiotics



Prebiotics

In 2010, the International Scientific Association for Probiotics and Prebiotics Working Group defined dietary prebiotics as “selectively fermented ingredients that result in specific changes, in the composition and/or activity of the gastrointestinal microbiota, thus conferring benefit(s) upon host health." The majority of identified prebiotics are carbohydrates of various molecular structures, naturally occurring in human and animal diets.

Typically, prebiotics are low molecular weight carbohydrates with 2 to 10 degrees of polymerisation. The main characteristics of prebiotics are resistance to digestive enzymes in the human gut but fermentability by the colonic microflora, and bifidogenic and pH-lowering effects. [3] By this last effect, prebiotics inhibits certain strains of potentially pathogenic bacteria, especially Clostridium, and prevent diarrhoea. [4]

The most prevalent forms of prebiotics are nutritionally classed as soluble fibre. Traditional dietary sources of prebiotics include soybeans, inulin sources (such as banana, Jerusalem artichoke, jicama, and chicory root), raw oats, unrefined wheat, unrefined barley, garlic, onion, raw wheat bran and cooked whole wheat flour. [5]


Types of prebiotics

The most widely described prebiotics are non-digestible oligosaccharides like fructooligosaccharides (FOS). [6] The others include polyols (xylitol, sorbitol, mannitol), disaccharides (lactulose, lactilol), oligosaccharides (raffinose, soybean), oligofructose, other non-digestible oligosaccharides (palatimose, isomaltose, lactosucrose) and polysaccharides (inulin, resistant starch). [7]

Fructooligosaccharides (FOS) are a naturally occurring oligosaccharide that is not digested in the upper gastrointestinal tract but is degraded in the colon by indigenous bacteria. It is a sweet product derived from native inulin and is approximately 30-60% as sweet as sugar.


Impact of probiotics and prebiotics on health

Figure 1: The impact of gut microbiota

Probiotics: The microbiota within the human distal gastrointestinal tract (GIT) is the largest ecosystem of the human body and it provides a unique situation to explore the effects of inflammatory processes. Evidence suggests that the bacterial load and the products of the intestinal microbiota might positively control inflammatory disease pathogenesis (Figure 1). [8, 9]


Diarrhoea

Diarrhoea is a major world health problem that has an impact on a number of deaths every day. Rotavirus is a key source of diarrhoea in young children. Probiotics can potentially contribute a significant means to reduce the occurrence of diarrhoea. The ability of probiotics to reduce the incidence or period of certain diarrheal illnesses is possibly the most significant health effect of probiotics. Coadministration of probiotics in patients on antibiotics significantly reduce antibiotic-associated diarrhoea in children. [10] Children with acute gastroenteritis who receive probiotic supplement (Lactobacillus rhamnosus, Lactobacillus reuteri, Lactobacillus casei) reported drastically decreased length of diarrhoea.


Inflammatory bowel disease (IBD)

Inflammatory bowel disease (IBD) is clinically characterised by two overlap phenotypes, Crohn’s disease (CD) and ulcerative colitis (UC), which mostly involve the colon (UC and CD) and/or the distal small intestine (CD). The intestinal bacteria are now supposed to be involved in the initiation and maintenance of IBD. Resident bacterial flora has been suggested to be an essential factor in driving the inflammatory process in human inflammatory bowel diseases. [11] Ecological factors such as the work and metabolic activity of the gut flora, immune system reactivity and genetic factors are all believed to play a role in the development of IBD states. The strain of Lactobacillus casei is capable of decreasing the number of activated T-lymphocytes in the lamina propria of Crohn’s disease, which may return the protected homeostasis. VSL-3 has been found to be a useful adjunct.


Irritable bowel syndrome (IBS)

The pathophysiology of irritable bowel syndrome (IBS) is not well known; however, alteration in the intestinal flora has been postulated as one of the etiologies. There is also no cure, so the treatment is mainly focused on symptom relief, and probiotics have been tried as a therapeutic modality. Probiotics may have an important benefit in preventing and treating IBS. Several controlled trials of probiotics in IBS have been published.

IBS symptoms, such as flatulence, bloating and constipation have been alleviated by organisms, such as Lactobacillus GG, Lactobacillus plantarum, Lactobacillus casei, Lactobacillus acidophilus, the probiotic ‘cocktail’ VSL-3 and Bifidobacterium animals. However, only a few products have been shown to affect pain and global symptoms in IBS. [12, 13,14] Numerous factors, including a reduction in gas production, changes in bile salt conjugation, an anti-bacterial or antiviral effect (in the case of post-infectious IBS), the promotion of motility, effects on mucus secretion or, even an anti-inflammatory effect, could be relevant to the benefits of specific probiotic strains in IBS.


Lactose intolerance

Worldwide, many millions of people experience lactose malabsorption. The frequency of the disorder increases with age. Lactose intolerance is a physiological state in human beings where they lack the ability to produce an enzyme named lactase or β-galactosidase. This lactase is essential to assimilate the disaccharide in milk and needs to be split into glucose and galactose. Individuals lacking lactase will not be able to digest milk and it often poses a problem in newborn infants. [15] This decline in activity results in lactose malabsorption. This incomplete absorption causes flatus, bloating, abdominal cramps, and moderate to severe diarrhoea. A major consequence of this sequence of events is a severe limitation in the consumption of dairy products, which is particularly pronounced in the elderly.

This beneficial effect is usually more associated with products fermented with Lactobacillus delbrueckii subsp. Bulgaricus and Streptococcus thermopiles. All yoghurts dramatically and similarly improved lactose digestion regardless of their total or specific β-gal activity.


Prebiotics- nutritional properties

The nutritional properties of prebiotics are related directly to the physiological changes they induce in the host. Bacterial metabolites are probably the main effectors of most observed effects. The most important metabolites are the short-chain fatty acids (SCFA) acetate, propionate and butyrate. Prebiotic consumption may double the pool of SCFA in the gastrointestinal tract. The postulated beneficial effects of prebiotics are summarised below.


Anti-carcinogenic effect

It has been suggested that prebiotics can be protective against the development of cancer. Secretion of carcinogens and tumour promoters by some species of bacteria of the colon can occur through the metabolism of certain types of food; proteolysis in the colon is recognised as a mechanism for the production of potentially malignant end products. [16] Modification of the gut microflora may interfere with the process of carcinogenesis and this opens up the possibility for dietary modification of colon cancer risk. Prebiotics modify the microflora by increasing the numbers of Lactobacilli and/or Bifidobacteria in the colon.

More pronounced effects were achieved by synbiotics and long-chain Inulin-type fructans compared to short-chain derivates (sustained activity of the saccharolytic fraction of the intestinal microbiota), especially in the more distal parts of the colon. [17]

Colorectal cancer is the third most common cancer, accounting for around 12% of cancer deaths worldwide. It is estimated that altering the gut microflora through diet towards the predominance of beneficial species could help in the prevention of the disease. The roles of short-chain fatty acids, for example, acetate, propionate and butyric acid are being extensively studied because they have shown to inhibit the growth of colon tumour cells, encourage cell turnover and support normal gene expression. [18. 19]


Anti-allergic effect

It is recognised that specific bacteria in the gut can potentially promote anti-allergenic processes. Different allergies affect different tissues and may have local or general effects. Some beneficial effects have been attributed to the consumption of these prebiotics. It is believed that their beneficial effects result from the metabolism of these compounds. Fermentation of these oligosaccharides results in the production of various organic acid and CO2. Delzenne and Roberfroidhave stated that the balance of such a complex process is likely to produce 40% SCFA, 15% lactic acid and 5% CO2.


Increased mineral absorption

Prebiotics have putative beneficial effects on calcium bioavailability. Calcium is mainly absorbed in the small intestine; however, some is also absorbed in the colon. Numerous animal studies have indicated that prebiotics increase calcium, iron, zinc, copper and magnesium absorption from the colon and stimulated the bacterial hydrolysis of phytic acid resulting in an improvement of absorption, increased bone density and bone trabecular structure. Intake of prebiotics acidifies the intestinal contents, which aids the solubilisation of minerals. Bacterial fermentation products, predominantly lactate and butyrate enlarge the absorption surface by promoting the proliferation of enterocytes.


Other potential health benefits

Prebiotics are helpful in modulating the immune system. It has been observed that the consumption of inulin-type fructans increases the phagocytic capacity of macrophages. There is increasing evidence from animal studies that the addition of fermentable fibre to the diet can modulate the type and function of cells from different regions of the gut-associated lymphoid tissue (GALT). Furthermore, prebiotics improved the manifestations of atopic dermatitis in children above two years and reduced the incidence of atopic dermatitis during the first six months of life in high-risk infants.

Fructo-polysaccharides such as inulin are non-digestible carbohydrate substrates in the diet that targets certain apparatus of the gut microbiota in the human large intestine such as Bifidobacterium and Lactobacilli. Inulin can stimulate the growth and/or activity of these types of bacteria in the colon and this stimulation can improve the intestinal flora composition, enhance the immune system and thereby contribute to the health of the host. Prebiotics increase faecal bulk and optimise stool consistency primarily by increasing faecal microbial mass. All carbohydrates that reach the large intestine have a laxative effect on bowel habit. It can be predicted, therefore, that prebiotics will be laxative. In carefully controlled studies it has indeed been shown that prebiotics that is fermented completely increase bowel frequency bringing relief from constipation in chronically constipated subjects.

Evidence suggests prebiotics can favourably influence serum glucose and insulin levels in a variety of ways. Digestion resistant oligosaccharides and other prebiotics can reduce the amount of glucose available for absorption into the bloodstream. [20] Prebiotics also prevent excessive blood glucose elevations after a meal by delaying gastric emptying and/or shortening small intestine transit time. Bacterial fermentation yielding short-chain fatty acids is another mechanism whereby prebiotics can modulate glycemia and insulinemia. [21]


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Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

The author, Dr. Manish S Bhatnagar is a Consultant Gastroenterologist, Hepatologist and Therapeutic Endoscopist from Ahmedabad.

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