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| REVIEW ARTICLE |
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| Year : 2021 | Volume
: 1
| Issue : 1 | Page : 11-16 |
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Probiotics in gastroenterology
L Thayumanavan, M Tarakeswari, K Muthukumaran
Department of Medical Gastroenterology, Westminster Health Care, Nungambakkam, Chennai, Tamil Nadu, India
| Date of Submission | 06-Aug-2020 |
| Date of Acceptance | 16-Aug-2020 |
| Date of Web Publication | 04-Dec-2020 |
Correspondence Address:
L Thayumanavan
Westminster Health Care, Nungambakkam, Chennai - 600 034, Tamil Nadu
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/ghep.ghep_13_20
Probiotic bacteria have become increasingly popular in the last two decades because of expanding scientific evidence pointing to their beneficial effects on human health. Currently it has become an attractive area of research in communicable and non communicable diseases. Their benefits are not only seen in GI diseases which are expected, but also seen in life style diseases like NAFLD and Cancer. This article provides a review of available information and summarizes the recent knowledge on the effects of prebiotics, probiotics and synbiotics on human health.
Keywords: Disease, gastrointestinal tract, health, microbiota
How to cite this article:
Thayumanavan L, Tarakeswari M, Muthukumaran K. Probiotics in gastroenterology. Gastroenterol Hepatol Endosc Pract 2021;1:11-6 |
| History | |  |
The health benefits of probiotics have been common knowledge since ages, but it is not until the dawn of this decade that we see renewed interest in gut microbial milieu and the role of probiotics in its maintenance, prevention, and treatment of certain diseases. It has been almost a century since Tissier observed that gut microbiota of healthy breastfed infants had a surplus of bifidobacteria, a microbe that was deficient in infants with diarrhea. It was the Russian scientist Metchnikoff who suggested that ingestion of fermented milk which had healthy microbes ameliorated the symptoms of diarrhea heralding the era of probiotics. During the world war, German scientist Alfred Nissle isolated nonpathogenic bacteria from the stool of a soldier who did not develop enteritis during an outbreak of shigellosis. The nonpathogenic microbe Escherichia coli strain Nissle 1917 is the earliest example of probiotic. The term “probiotic” was coined by Lilley and Stillwell in the year 1965.[1] Later, Fuller defined them as “a live microbial food supplement which beneficially affects the host animal by improving its microbial balance.”[2] Since then, numerous studies have been published that demonstrate the health benefits of various strains of microbiota and their role as therapeutic agents. Some of the reported health benefits of probiotics include amelioration of lactose intolerance, decrease in the symptoms of antibiotic-associated diarrhea noted with strains of lactobacilli, and bifidobacteria.[3],[4] The food market has also been expanding, with probiotics being the latest food fad. Although growing evidence of their health benefits has been observed, rare safety concerns have also been raised and more research is warranted to prove their role in disease and health.
Gut microbiota
The intestine is colonized with a huge number of microbial strains, predominantly in the colon that, in symbiosis with the host, plays multiple roles in human health. The human colon harbors approximately 40 trillion bacterial cells and a few fungi and viruses. Microbial diversity is remarkable between individuals as although the predominant strain is Bacteroides and Firmicutes, there is a distinctive pattern of microbes in each individual which is acquired from birth and dietary habits.[5] The human heart and brain are the only organs that are not colonized by bacteria. The gut of the newborn is colonized soon after birth by facultative anaerobes such as Escherichia and Enterococcus enabling shift to Firmicutes, especially bifidobacteria. This is the primary microbiome educating developing immune system and other microbial colonization having lifelong implications. This is dependent on maternal genetics, environmental exposures, breastfeeding, and vaginal delivery. Probiotics not only exhibits vertical transmission but a multitude of properties like stability, resilience and plasticity which are enumerated in [Table 1].[6],[7],[8]
| Definitions | | |
The definition of probiotic currently in vogue is the one given by the World Health Organization according to which probiotics are redefined as “live microorganisms which when administered in adequate amounts confer a health benefit on the host.” In relation to food, the definition can be adjusted by emphasizing that the beneficial effect is exerted by the microorganisms “when consumed in adequate amounts as part of food.”[9]
The prebiotic concept is a more recent one than probiotics and was first proposed by Gibson and Roberfroid in 1995.[10] Prebiotics are substances that are indigestible but confer a health benefit to the host by acting on the native microbes in the host. Some of the commonly known prebiotics include fructose, oligosaccharide, lactulose, and inulin. Prebiotics are present in dietary substances such as dairy products and many natural food substances such as honey and wheat.
Synbiotic is a combination of prebiotic and probiotic in the appropriate proportion [Table 2]. The different species of probiotics is enlisted in [Table 3].[11]
Microbial species as probiotics
For a microbe to function as probiotic, it must possess certain desirable properties which are usually tested in vitro.
Some of these include:
- Acid and bile tolerance which seems to be crucial for oral administration
- Adhesion to mucosal and epithelial surfaces, an important property for successful immune modulation, competitive exclusion of pathogens, as well as prevention of pathogen adhesion and colonization
- Antimicrobial activity against pathogenic bacteria
- Bile salt hydrolase activity.
The probiotic dose as determined by the colony-forming units per gram is an important parameter that determines its efficacy in humans. It is generally accepted that probiotic product should have a minimum concentration of 106 CFU/mL or gram and that a total of some 108 to 109 probiotic microorganisms should be consumed daily for the probiotic effect to be transferred to the consumer.
Everyday food items as probiotics
Probiotics may be present in our day-to-day food items such as yogurt, cheese, and sauerkraut. Cheese contains both lactobacilli and prebiotic fiber in the form of inulin. In a study by Ahola et al., it has been demonstrated that regular consumption of cheese has been associated with reduced incidence of Campylobacter enteritis and dental caries by its action on salivary yeasts.[12] Food products as a means of probiotic delivery have a growing application. Nondairy food products such as soy-based foods, cereal bars, and juices are being tried as an effective means of probiotic delivery.[13] Multiple factors determine the effectiveness of incorporating a probiotic strain in a food product, which include safety, compatibility, and maintenance of its viability. Microencapsulation technology maintains the viability of probiotic and also enables easy delivery. Spore formulations are also available that can be easily incorporated into food products.
The indications for the use of probiotics(as in [Table 4]) are ever increasing and proof of its effectiveness is being appreciated.[14] The number of research articles is increasing not only in their use in gastrointestinal (GI) disorders but also in liver diseases, dyslipidemia, cancer, urinary infections, etc. The benefits and mechanism of probiotic-host interaction are shown in [Table 5].[15]
Mechanisms of action
Probiotics affect the microbial milieu of the intestine in several ways by impacting mucosal immune mechanisms, by interacting with commensal or potential pathogenic microbes, by generating metabolic end products such as short-chain fatty acids, and by communicating with host cells through chemical signaling. These mechanisms can lead to antagonism of potential pathogens, an improved intestinal environment, bolstering the intestinal barrier, downregulation of inflammation, and upregulation of the immune response to antigenic challenges.
Are probiotics food or drug?
There is a wide range of probiotic products available in the market from food supplements to prescription drugs, and the onus lies on the prescribing physician to decide on the necessity and the reason for prescribing the probiotic combinations as exemplified in [Table 6].
Clinical applications
Antibiotic-associated diarrhea
Mild-to-severe forms of diarrhea have been seen with prolonged use of antibiotics.
This may range from mild diarrhea with no mucosal changes to the severe form with pseudomembranes also called Clostridium difficile colitis. It is usually treated by withdrawing the causative antibiotic and sometimes with metronidazole or vancomycin. There are several studies which show that probiotics prevent this condition. The use of probiotics Lactobacillus rhamnosus and Saccharomyces boulardii has been shown to be beneficial in the treatment also.[16],[17]
Infectious diarrhea
One of the most commonly used applications of probiotics is in the prevention and treatment of infectious diarrhea in children. Rotavirus infection is quite common in childhood, and the severity of diarrheal episodes can be reduced with the use of probiotics. There are many studies have which have shown that probiotics such as L. rhamnosus GG, Lactobacillus reuteri, Lactobacillus casei Shirota, and Bifidobacterium animalis Bb12 can shorten the duration of acute rotavirus diarrhea with the strongest evidence pointing to the effectiveness of L. rhamnosus GG and B. animalis Bb12.[18],[19]
Prevention of cancers
There are several different mechanisms of carcinogenesis, and the role of harmful enteropathogens is one of them. Various enteropathogens like Clostridium perfringens produce beta-glucuronidase and nitroreductase that convert procarcinogens to carcinogens. Probiotic bifidobacteria lowers the intestinal pH and creates a bactericidal environment that prevents the growth of harmful bacteria. Studies have also demonstrated that bifidobacteria induces phagocytes that act on tumor cells, hence preventing their growth.[20] Reddy and Riverson demonstrated that dietary Bifidobacterium longum cultures significantly suppressed the expression of total and neonatal RAS p21 in the colonic mucosa and tumors compared with control diet.[21] Also probiotic strains Lactobacillus rhamnosum and Lactobacillus planatorum have also been shown to be beneficial in chemotherapy related toxicity.
Irritable bowel syndrome
A 2015 meta-analysis of 24 human clinical trials concluded that probiotics overall were more beneficial than placebo in reducing pain and symptom severity scores.[22] A 2016 meta-analysis conducted by the British Dietary Association concluded that of the 35 trials analyzed, most showed good outcomes with the use of probiotics in IBS.[23] Of the various strains, it has been demonstrated that Bifidobacterium longum and Bifidobacterium infantis hold good promise in therapy. There has been a rising debate as to single strain versus multistrain probiotic in the treatment of IBS. Of the studies that demonstrated a statistically significant improvement in the global outcomes and more specifically abdominal pain, it was found that the use of multistrain probiotic was more effective.[24]
Inflammatory bowel disease
Probiotics have been found to achieve higher remission rates in mild-to-moderate ulcerative colitis. In pouchitis, the use of probiotic mixture has been shown to effectively reduce relapses after the control of infection. However, probiotics have not been shown to be of much benefit in Crohn’s disease.
Necrotizing enterocolitis
Preterm infants are prone to necrotizing enterocolitis which can be prevented by the use of probiotics. Studies have demonstrated the lower prevalence of protective bacteria lactobacilli and bifidobacteria making probiotics a potential agent for prevention.
Atopic dermatitis and cow milk allergy
The role of probiotics in controlling atopic dermatitis in infants was studied by Kirjavainem et al. They conducted a double-blind randomized study in which the study population used the infant formula as the control group but superadded with viable probiotic strain Lactobacillus GG. The study demonstrated that the symptoms and signs were alleviated with the use of viable probiotic.[25]
Food allergy
Probiotics decrease the IgE response to food allergens and thereby a decreased allergic response to food.[26] Bifidobacteria and lactobacilli potentiate IgA response to harmful bacteria in Peyer’s patches.[27] Probiotics reduce the secretion of th2 cytokines such as interleukin (IL)-3, IL-4, IL-6, IL-9, and IL-10 which are responsible for the production of IgE and eosinophils in response to allergic antigens.
Helicobacter pylori eradication
The Maastricht V consensus guidelines for Helicobacter pylori management recommended that probiotics can be used to reduce the side effect of antibiotic use in H. pylori treatment. It has also been shown to improve the eradication rate of H. pylori,[28] but it can only be used as an adjunct, and monotherapy does not act against H. pylori.
Lactose intolerance
Probiotics, especially strains of lactobacilli, have been shown to ameliorate the symptoms of lactose malabsorption.[29]
Nonalcoholic fatty liver disease
Probiotics have a beneficial effect on metabolic syndrome and show improved values of transaminases in steatohepatitis. Numerous studies[30],[31] have demonstrated that probiotics improve the HOMA score and decrease fat deposition in the liver.
Bacterial vaginosis and recurrent urinary tract infection
Antimicrobials are the drug of choice for urinary tract infection and vaginitis, but the altered microflora has been found to be associated with recurrence. Studies have demonstrated that probiotics like L. rhamnosus, a distal urethral isolate, reduce the frequency of episodes. The organisms that are freeze-dried are delivered in gelatin capsules which ensure that optimal doses reach the vagina.[32]
Dyslipidemia
Probiotics have been shown to have lipid-lowering effects in numerous studies. They act by utilizing the fat and converting them to metabolic end products which prevent their conversion to cholesterol.[33] This lipid-lowering effect is only modest and hence can be used as adjuvant therapy.
Safety profile
Probiotics though safe have shown instances of infection and bacteremia, especially in the immune compromised. The estimated incidence of such reports of infective endocarditis and bacteremia is 0.05%–0.4%.[34] Clinical studies done on specific immunocompromised groups like HIV-infected patients have demonstrated the safety of probiotics. There is no evidence that ingested probiotics pose any risk of sepsis than commensal strains. In quantitative terms, the risk of bacterial sepsis is <1 case per million individuals. Vigilance regarding rare cases of infections due to probiotics should be maintained for confirmation by molecular characterization. The long use of probiotics and the extreme rarity of complications is proof of their relative safety.
Transplanting microbes – Fecal microbiota transplant
The role of microbes in health and disease has been more emphatically confirmed by fecal microbiota transplant which has shown promise in therapy of many GI disorders, particularly C. difficile-associated colitis. Fecal microbiota transplantation (FMT) is the administration of a solution of fecal matter from a donor into the intestinal tract of a recipient in order to directly change the recipients’ gut microbial composition. Apart from pseudomembranous colitis, it has been found to be effective in inflammatory bowel disorders, obesity, metabolic syndrome, and other functional GI disorders. Advances in the method of delivery of FMT are being investigated to avoid the cumbersome procedure of delivery of the fecal microbiota to the colon via enemas, colonoscopy, or nasogastric tubes. It is surprising that fecal contamination which was thought to be disease producing has turned a full circle, with FMT being therapeutic in certain diseases. Bugs (bacteria) which was once considered to be causing diseases are now considered as disease modifying agents and used in therapy.
| Conclusion | | |
Probiotics have a definitive role in health and disease as evidenced by the scientific research. This has led to it becoming a food fad as well, with the introduction of yoghurt and other dairy products incorporated with probiotics. Furthermore, increased consumer acceptance of probiotics is now seen. The prescription of probiotics as first-line therapy is still debatable and is a long way off, and more robust research is needed to prove its efficacy. The appropriate strain for the disease, as well as the dose needed for the same and the duration of treatment, needs to be defined. It can be safely prescribed as an adjunct therapy in the aforementioned diseases with remarkable benefit. The market place for probiotics is still in its infancy with more scope in the method of delivery and products available. Probiotics are here to stay, and it heralds the dawn of a new era where microbes and not antimicrobials are used for medical therapy.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]
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