Most of our gut microbiota live with us in a mutually beneficial life-long relationship. The gut microbiota plays a vital role in the host’s overall health through its metabolic activities. Human microbiota might be supported by consuming friendly bacteria (probiotics) and consuming foods to improve the microbiota (prebiotics). During the last two decades, probiotics’ interest has increased with rising scientific shreds of evidence of benefits on human health. Hence, they have been exploited as various food products, mainly fermented foods. Probiotics as a treatment modality may restore normal microbiota and functioning of the gastrointestinal (GI) tract. Strong scientific evidence is associating these bacteria with the prevention and therapy of various GI disorders. (In light of the ongoing trend of probiotics, further research is needed to obtain the perspective of potential applications for better health. Probiotic applications have been extended from health applications to food and agricultural applications. The benefits of probiotics led to its applications in probiotic ‘health food’ industries and agricultural sectors.
- Food products
- Gut microbiome
The human body exists in close relation with numerous structurally and functionally diverse microbes inhabiting different parts of the body. The mouth, the gastrointestinal tract (GIT), and the vagina are most heavily populated. This composition is known as microbiota which is acquired soon after birth . The microbiota that is exclusively found in GIT is referred to as ‘Gut microbiota.’ Gut microbiota is primarily non-pathogenic and plays a vital role in conferring health benefits to the host .Through metabolic activities and physiological regulation such as resistance to pathogens, improvement of intestinal barrier function, promotion of nutrient absorption, formation of bioactive compounds . It may also influence the physiology, biochemistry of the host .
The idea that bacteria can confer health benefits to humans was postulated 100 years ago by Elie Metchnikoff. The ‘probiotic’ word is derived from the Greek word, meaning “for life” and has had several different meanings over the years . The increase in evidence of the benefits of probiotics and prebiotics, especially in health improvement, led to its applications in various food industries. This book chapter highlights the significance of gut microbiota and the emergence of probiotic concepts to benefit human health. In this chapter, we have made a little attempt to introduce the concept of probiotics and prebiotics, their benefits to humans’ health, and their probability of being applicable in various fields.
2. Gut microbiota
The human body harbors a complex ecosystem that includes more than 1000 various microorganisms [5, 6]. It means the number of bacteria within the gut is about ten times that of eukaryotic cells in the human body. In a healthy animal, the internal tissues such as blood, brain, muscle, etc. in a healthy animal are usually free of microorganisms. However, the surface tissues, such as skin and mucous membranes, are constantly in contact with environmental organisms and become readily colonized by various microbial species. The microbiota extends from mouth to anus and into the vaginal tract of women. In the healthy host, enteric bacteria colonize the alimentary tract soon after birth, and the composition of the intestinal microbiota remains relatively constant . The normal flora of humans consists of a few eukaryotic fungi and protists, but bacteria are the most numerous and obvious microbial components of the normal flora. The total genomic content of microbiota is referred to as a microbiome that inhabits a specific anatomical site of the body . The mixture of organisms regularly found at any anatomical site is referred to as the “normal flora”. However, researchers in the field who prefer the term “indigenous microbiota,” which includes resident microbiota, transient microbiota, and opportunistic microbiota.
The gut microbiome exhibits various interactions with the human body. It may be mutualistic or pathogenic. The interactions between the gut microbiome and host have evolved into symbiotic relations. It confers various benefits to the human body, significantly strengthens the host’s immune system, and protects against various diseases caused by harmful pathogens. Hence, it is helpful to study the symbiotic relationship of the gut microbiome with the host and its influence on the host’s overall health.
2.1 Composition of gut microbiota
The gut microbiota is composed of four main phyla: Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria. Predominantly, anaerobic bacteria colonize the Gastrointestinal tract (GIT) .
GI tract consists of the stomach, small intestine, and large intestine. Various parts of the GI tract differ in their environmental characteristics, chemical compositions, and physiological properties. Therefore types and numbers of microbiota vary in different parts. In general, microorganisms increase in numbers from the stomach to the small intestine to the large intestine.
2.1.1 Microbiota of stomach
The microbes in the stomach are primarily of similar types that are present in the mouth and throat. Generally, aerobic microbes inhabit the stomach, and that too in a lesser amount than the population of mouth and stomach. The stomach receives many microbes from the mouth through food and water, but most of them are killed due to hydrochloric acid (HCl). Thus, few microorganisms that can tolerate high pH can form normal resident flora of the stomach.
Organisms generally found in the stomach are –
2.1.2 Microbiota of small intestine
The small intestine is a tube about 6 meters long-running from the stomach to the large intestine. The small intestine usually has three sections: duodenum, jejunum, and ileum. Each section reflects slightly different functions. The microbiota of the small bowel is the least well understood due to its inaccessibility for study.
Duodenum is adjacent to the stomach, and it is slightly acidic. The duodenum includes similar types of organisms that are found in the stomach. It mainly acquires acid-resistant organisms such as Lactobacillus and Enterococcus. The intestine becomes less acidic from the duodenum to the ileum; hence, the microbial population increases. In the jejunum, prominently, lactobacillus, Enterococci,
2.1.3 Microbiota of large intestine
The large intestine follows on from the small intestine. The large intestine receives remains of food that enzymes have not digested. The chyme, on entering the large intestine, is referred to as feces. The large intestine is divided into three distinct parts: caecum, colon, and rectum. About 1100 different species of microbes are present in the large intestine .
The large intestine harbors obligate anaerobes and facultative anaerobes. The more common genera include Bacteroides,
2.2 Benefits of gut microbiota
Earlier, the gut microbiota was thought to be commensals whose only benefit was controlling the abundance of pathogenic bacteria. However, as the knowledge about these symbionts increased, their essential roles, such as aiding digestion and various metabolites, were also known to improve the immune system [17, 18]. The gut microbiota plays a crucial role in immunomodulation and the nervous system and intestinal mucosal system development. In addition, gut microbiota plays a crucial role in synthesizing essential vitamins such as vitamin B12, vitamin K, nicotinic acid, pyridoxine, thiamine . The gut microbiota generates short-chain fatty acids (SCFAs) by fermenting complex carbohydrates. These SCFAs play a significant role in inflammatory response and regulation of immune response. The gut microbiota also influences epithelial homeostasis .
There are pieces of evidence that gut microbiota provides extra nutrition. It could be due to the digestion by enzymes of the resident microbiota. Another benefit of gut microbiota is a defense against a range of pathogens, including
2.3 Disturbance of gut microbiota
The composition of gut microbiota may vary between individuals though some key bacterial species are typically present in most. Diet is thought to explain over 50% of these microbial structural variations in mice and 20% in humans, signaling the potential for dietary strategies in disease management through gut microbiota modulation . The gut microbiota shows drastic changes in infants with lactation followed by an introduction to solid food. The mode of intake, medication dosage may influence the gut microbiota. Gut microbes are regularly purged and have the ability to double in specific time intervals. The short-term and long-term dietary changes and modification in micronutrient intake can significantly change gut microbiota composition. The experiment conducted by Wu et al. showed a dramatic shift in the fecal microbiota of the participants due to high fat/low fiber and low fat/high fiber. Fiber content and type were thought to be primer determinants of the composition of the microbiota of the gut.
Through antibiotics, improvement in human health is achieved through the drugs have negative consequences also. Antibiotic drugs control the infections caused by pathogens, but other beneficial bacteria are also harmed. A disturbed microbiota may not function well against infections caused by new pathogens, resulting in the overgrowth of pathogens such as
Most antibiotics are taken orally, and some are given intravenously. The latter type has a significant influence to disturb microbiota. Different antibiotics have different effects, e.g., penicillin has minor effects on the gut microbiota, while ampicillin causes significant disturbance to the gut microbiota. Thus, there is a need to develop an alternative that is safer and effective for use. Increasing knowledge of probiotics and their efficacy against pathogens can aid the recovery of gut microbiota. Probiotics may be suitable to take after or simultaneously as antibiotics to reduce the risk of disease from disturbance of microbiota.
Probiotics are live organisms which when administered in an adequate amount, confers health benefits to the host (FAO and WHO, 2002). The characteristics of effective probiotics are their ability to survive the passage through the digestive tract and utilize the nutrients and substrates in a normal diet. Probiotics are healthy gut flora and thereby improve digestion. Several criteria have been used to prove any strain as novel probiotic strains, categorized into two groups: safety and functionality. The concept of probiotics deals with the constant introduction of the new microbes beneficial to the human host as an attempt to change the indigenous microbial population equilibrium to increase overall health .
3.1 History of Probiotics
The concept of using microbes to improve health is a hundred years old. During the twentieth century, probiotics gained much interest due to an increase in scientific evidence proving the beneficial effects of probiotics. The idea that bacteria could benefit human health was postulated almost 100 years ago by Elie Metchnikoff while working at the Pasteur Institute in Paris. Metchnikoff’s adoption of an idea to use beneficial bacteria to improve the bacterial population of the intestine arose from his inquiries into how old age could be delayed and life prolonged. Metchnikoff concluded that fermented milk drank by peasants of Bulgaria has a key role (Metchnikoff 1907)  in their longevity. He found a bacterium from peasant’s milk and named it
The term probiotic literally means ‘for life is derived from the Greek language. Lilly and Stillwell first coined this term in 1965 to describe “substances secreted by one microorganism which stimulates the growth of another” and thus was contrasted with the term antibiotic . Parker modified this definition to “organisms which contribute to intestinal microbial balance” . The concept of probiotics became weak after the early death of Metchnikoff and the development of antibiotic drugs. Though, interest in the general public did not fall entirely. One of the factors that gained the popularity of probiotics towards the end of the century is the rise of resistant strains of pathogens against different antibiotics.
3.2 Mechanism and action of probiotics
The mechanisms of probiotic action are diverse. The activities of these strains can influence other factors such as the presence of other bacteria in the intestinal environment or even the disease setting in which the strain is being used . The characteristics of effective probiotics are their ability to survive the passage through the digestive tract and utilize the nutrients and substrates in a normal diet. However, some mechanisms have been reported for most of the probiotic strains, which include: colonization resistance, antimicrobial activity, antimutagenic effects, antigenotoxic effects, influence on enzyme activity, etc.
The probiotic bacteria have antagonistic effects on different microorganisms and competitive adherence to mucosa and epithelium. These characteristics also work as antimicrobial activity. By decreasing luminal pH, they are inhibiting other bacterial adherence, translocation, and secretion of antimicrobial substances such as antimicrobial peptides (e.g., bacteriocin), organic acids (lactic and acetic acid), hydrogen peroxide (in environments in which oxygen is present), diacetyl, β-hydroxypropionaldehyde [26, 27, 28, 29, 30]. The probiotics are also capable to modulate cell proliferation and apoptosis. Polysaccharide fermentation by probiotic strains increases the availability of short-chain fatty acids (SCFAs), which felicitate repair of epithelial damage. Some strains also produce mucus excessively, which enhances the intestinal barrier. It can separate bacteria from the lumen and prevent the colonization of the epithelium . Probiotics can exert control over epithelial cells, dendritic cells, monocytes, macrophages, lymphocytes, IgA through different mechanisms for the stimulation of the human immune system; increased IgA decreases the number of pathogens, thus improving gut health [32, 33]. Figure 1 shows various mechanisms by which probiotics benefits health of host.
3.3 Types of probiotic microbes
There is a growing number of microorganisms described as probiotics. Among the various types of microbes, bacteria are used as probiotics mainly. The potential of intestinal and dairy species Lactobacilli and Bifidobacteria as probiotics was postulated over a hundred years ago. At that time, the yearning to understand the microbial ecology of these groups in the human intestine was linked to the aspiration to manage and maintain human health. The link between Lactobacilli and human health was first proposed in the late 1800s by Metchnikoff .
The majority of the different species included in probiotics belong to the genus
Secretion of lactic acid lowers the pH of GIT and eliminates harmful bacteria. Some lactobacilli produce acetic acid, which gives a more substantial effect than lactic acid against pathogens.
Lactobacilli produce antibiotic-like compounds referred to as bacteriocins, which restrict the growth of pathogens. Some of them also produce hydrogen, which exerts antibacterial effects.
Lactobacilli tend to attach to mucosa and form colonies, which is the primary requirement of good probiotics. They block the attachment of pathogens and may also influence the immune cells in the gut wall. Some lactobacilli also produce mucus in excess to discourage attachment of pathogens.
There are other genera of lactic acid-secreting bacteria. One of them is
Bifidobacteria are the second most commonly used type of bacteria in probiotic products. One of the reasons for their less popularity could be their incapability to grow and process commercially. Henry Tissier identified the unusually shaped
Like lactobacilli and bifidobacteria, other organisms such as
|Probiotic Lactic acid bacteria|
4. Benefits of probiotics
There are certain diseases related to the disturbance of microbiota of the gastrointestinal tract. Some of them are infectious diarrhea, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), lactose intolerance, antibiotic-associated diarrhea, constipation, gastritis, and stomach ulcers. There are evidences available showing influence of probiotics to treat such diseases. Other body parts may benefit from probiotics as microbiota is present in other body parts, not just the intestine. Furthermore, the immune system is connected to all parts of the body, so by influencing one part of the immune system, probiotics may influence others.
4.1 Effect of probiotics on diarrhea
Infectious diarrhea, traveler’s diarrhea (TD), antibiotic-associated diarrhea are various types of diarrhea caused by different conditions. Infectious diarrhea is generally caused by pathogenic microbes such as viruses, bacteria, yeast, or protozoan. Generally, normal bowel movements return after about three days, but they may not in children with acute diarrhea. In infants, rotavirus is the most common microbe responsible for diarrhea. Probiotics have been tried in many clinical studies as a supplement for rehydration therapy to treat infectious diarrhea in infants. The results have been positive and consistent . In young children, the probiotics were also found to be effective in preventing the development of infectious diarrhea. The types of probiotic microbes used are lactobacilli, bifidobacteria,
The traveler’s diarrhea may be caused by the water supply being contaminated with fecal matter, contaminated food. In the case of traveler’s diarrhea, the use of probiotics is more likely to be considered by adults. Though, the use of probiotics in TD has given a mixed response as the cause of TD differs depending on the local situation .
The use of antibiotics has revolutionized the treatment of bacterial infections. However, it promotes the rise of resistant bacteria and disturbs gut microbiota’s composition, which makes us vulnerable to pathogenic infection. Such infection of the intestine leads to diarrhea, referred to as ‘antibiotic-associated diarrhea (AAD)’. When the gut microbiota is disturbed,
4.2 Effect of probiotics in Irritable Bowel Syndrome (IBS)
The irritable bowel syndrome is a common gastrointestinal disorder. In IBS an abnormal condition of gut contractions (motility) and increased gut sensations (visceral hypersensitivity) characterized by abdominal pain/discomfort, gas, bloating, mucous in stools, and irregular bowel habits with constipation or diarrhea. Several studies show the effect of probiotics on this disease; however, the mechanism by which probiotic organisms affect this condition is still unknown. A review and meta-analysis by Ford et al. concluded the beneficial effects of probiotics as a treatment on IBS symptoms, including RCTs published between 1939 and 2013, and it was emphasized that multi-strain probiotics had a more distinct effect on IBS symptoms [46, 47]. However,
4.3 Effect of probiotics in inflammatory bowel disease (IBD)
Inflammatory bowel disease is a group of the chronic intestinal disease characterized by inflammation of the large or small intestine. Crohn’s disease (CD) and ulcerative colitis (UC) are the most common types of IBD. UC only affects the large bowel, and the inflammation is usually found in the rectum and the sigmoid colon but can be found anywhere along with the large bowel. CD can affect any part of the digestive tube from mouth to the anus but is most often found in the area of the junction of the ileum and caecum. The evidence of benefit from probiotics in UC is strong, while the evidence in Crohn’s is weak. There have been eight controlled trials involving people with UC in one study, and seven of them showed significant benefit from probiotics. Use of probiotics extended periods of remission or reduced active disease . Some studies have been conducted with
4.4 Effect of probiotics in lactose intolerance
The inability of some adults to digest the sugar lactose, which is present in milk, is referred to as ‘lactose intolerance. The lactose is hydrolyzed by the enzyme lactase, which is also known as lactose- galactosehydrolase (EC 18.104.22.168). The lactose is digested into glucose and galactose, which is taken up by intestinal cells and transported to the bloodstream. The remaining lactose, which is not hydrolyzed, passes to the colon . The person with lactose intolerance produces less lactase, which is inefficient in digesting much of the milk sugar. The undigested lactose causes intestinal difficulties. When lactose intolerant people consume milk, they may suffer from excess gas, diarrhea, cramps, bloating, abdominal rumblings, and flatulence. One of the reasons for excess gas could be the fermentation of glucose by gut microbiota. As lactose is an active osmotic compound, it causes osmotic pressure, leading to high water content in the feces, causing clinical symptoms as diarrhea . Probiotics have gained attention as an alternative to compensate for the low level of lactase [41, 50]. Probiotic can affect at two levels: (i) By increasing hydrolytic activity in the small intestine (ii) By increasing colonic fermentation . Several studies have shown the effect of probiotic yogurt in better lactose digestion in lactose-intolerant people. The probiotic bacteria used in yogurt (
4.5 Effect of probiotics in gastritis and stomach ulcers
The growing interest in probiotics to prevent or treat gastrointestinal diseases has attracted the attention of many researchers to explore the role of probiotics in the prevention and treatment of gastric ulcers . Some studies have found out that when probiotics are used in conjunction with standard drugs, the rate of eradication was higher than drug therapy or probiotics alone . However, side effects caused by drug therapy were reduced by probiotics. Most of the studies have used lactobacilli, but not all strains showed effects against
4.6 Effect of probiotic in vaginal infections
In a healthy woman, the vagina has a resident microbial population. These resident microbiota live on the lining of the vagina wall. Most of them are lactobacilli. The vaginal lactobacilli have a protective influence against urogenital infections . The vaginal infections are referred to as vaginitis. In which pathogenic infections cause inflammation of the vaginal lining. If a bacterium causes vaginitis, it is known as bacterial vaginosis (BV). If vaginitis is caused by a fungus (generally
4.7 Effect of probiotics in upper respiratory infections
The upper respiratory tract (URT) consists of the nose, throat, and windpipe. The nose and throat have microbiota, and the upper part of the windpipe has a changing microbial population as cilia move mucus upward to the throat. The various diseases associated with URT are common cold, sore throat, pharyngitis, epiglottitis, laryngitis, and diphtheria . Most commonly, viruses such as rhinoviruses, coronaviruses, parainfluenza, and influenza viruses and bacteria such as streptococci,
4.8 Effect of probiotics in constipation
Constipation is quite a common condition that can be acute or chronic. Constipation causes a general feeling of abdominal discomfort. To pass the stool straining may put pressure on the tissues and structures of the anal area with adverse consequences such as hemorrhoids (piles). Other diseases associated with constipation are irritable bowel syndrome and cancer of the large bowel. Several studies have been conducted using
4.9 Other benefits
The list of benefits of probiotics is not limited to the ones mentioned above. However, it includes a range of benefits that need to be explored for further human studies. Some evidences suggest that probiotics may influence cancer incidence . As well as researchers are exploring various alternatives of drugs from probiotics that can be used to treat a disease like cancer and with lesser or no side effects. (i.e., L-asparaginase that is used in cancer treatment from
5. Application of probiotics
Due to the health benefits exerted by probiotic organisms, they have a wide range of applications in clinical uses and various industries such as food industries and agriculture industries. Most species of lactobacilli and bifidobacteria are used commercially. Among them
5.1 Application of probiotics in the food industry
Increasing knowledge of probiotic benefits leads to the development of functional foods. Functional foods, also known as “nutraceuticals” or “designer foods,” are ingredients that offer health benefits that extend beyond their nutritional value. Some types contain supplements or other additional ingredients designed to improve health, and they are slowly emerging as ‘health food’ on supermarket shelves worldwide . A wide variety of dairy products such as milk, yogurt, cheese, ice cream, chocolate mousse, quark, etc., include probiotic organisms to improve their nutrition characteristics [70, 71, 72, 73, 74]. Furthermore, whey-based and fortified dairy beverages are also available, including probiotic and
|Food product||Probiotic organism used||References|
|Yogurt, bio-yogurts||[76, 80, 81]|
|Kefir (Fermented milk beverage)|||
|Yosa (oat-bran pudding)|||
|Kombucha (Fermented tea beverage)|||
|Kimchi (Fermented vegetable dish)|||
5.2 Application of probiotics in agriculture
Other than human, probiotics application is extended to agriculture as well. One of them is probiotic farming, which is referred to as bio-intensive agriculture that combines various organic farming techniques to make soil healthier. It introduces beneficial microorganisms into the growing environment. The use of probiotics increases crop yield, limits the need for harmful fertilizers and pesticides and depletes damages caused by them. Probiotics also amplify plant’s resistance to pests and diseases. Due to antagonistic effects exhibited by probiotic bacteria by ‘induced systemic resistance,’ plants are protected from pathogenic microorganisms.
5.3 Application of probiotics in clinical use
As described earlier, probiotics prevent or mitigate various diseases and severe symptoms by various mechanisms, but it is advisable to take care when used in immune-compromised patients. Encouraging evidences are emerging for probiotics’ efficiency in the management of pouchitis and pediatric atopic diseases. Probiotics are also helpful in preventing postoperative infections . There is strong evidence that some bacterial strains are efficient in enhancing immune function. Probiotics are also beneficial in mental disorders and reduce carcinogenic activity, cholesterol level, and blood pressure . The significance of probiotics in preventing traveler’s diarrhea, sepsis-associated with severe pancreatitis, ulcerative colitis, and reduction of hyper cholesterol is unproven [89, 90]. The chemotherapeutic drugs such as L-asparaginase with fewer side effects from probiotic bacteria are still being explored. A study reported the use of kimchi to treat cancer . Furthermore, the development of alternative antibiotics such as lantibiotics, antimicrobial peptides (AMPs) from probiotic bacteria are being explored to reduce side effects caused by traditional drug therapies and as a next-generation drug system against resistant pathogens. LAB bacteriocin- Nisin is commercially used as a food preservative . It also has biomedical applications as it exhibits antimicrobial activity against resistant pathogens and anti-biofilm properties to use in combination with therapeutic drugs . Although probiotics have shown encouraging evidence of efficacy in various diseases, there is much exploration needed for standard clinical practice in humans.
Exploration of gut microbiota indicates that beneficial gut microbiota plays a crucial and constructive role in maintaining the health of host (human). The symbiotic relation of gut microbiota with host and benefits exhibited by them leads to the development of probiotics and prebiotics. Studies on various mechanisms of probiotics have shown their abilities to prevent or treat various diseases in human. Due to this efficiency, probiotics and prebiotics and their applications in various fields have shown a substantial increase in the last two decades. Probiotics are mainly applied in the food industry to develop functional foods and supplements to benefit consumers. The applications of probiotics are also extended to the agriculture industry to boost the productivity and quality of crops and animals. The emergence of encouraging evidence has given a sight to use probiotics in clinical practices with minimum side effects. However, clinical use of probiotics as standard practice is under the umbrella of research yet.