Open access peer-reviewed chapter

Prebiotics, Probiotics, and Bacterial Infections

Written By

Christina C. Tam, Kirkwood M. Land and Luisa W. Cheng

Submitted: 01 July 2019 Reviewed: 07 August 2019 Published: 03 October 2019

DOI: 10.5772/intechopen.89052

From the Edited Volume

Prebiotics and Probiotics - Potential Benefits in Nutrition and Health

Edited by Elena Franco-Robles and Joel Ramírez-Emiliano

Chapter metrics overview

1,025 Chapter Downloads

View Full Metrics


Bacterial pathogens have developed exquisite virulence mechanisms to survive in the host cells. These virulence mechanisms help them bind and internalize into host cells, replicate, and evade the host immune response. The mammalian host itself has developed its own repertoire of weapons to prevent this from happening. One important component of host response in preventing infections in the gut lumen is the diverse commensal microbiota present. Dysbiosis of the gut microbiota has been implicated in the development of many gastrointestinal diseases. A potential therapeutic pathway to solve these diseases would be by providing probiotics and/or prebiotics to help stimulate growth of the beneficial commensal bacteria. Here, we will present evidence of commensal microbiota imbalance in the development of disease as well as potential therapies to restore gut harmony.


  • probiotics
  • bacterial infections
  • prebiotics
  • microbiota
  • therapeutics

1. Introduction

Probiotic microorganisms have been extensively studied for their beneficial effects in not only maintaining the normal gut mucosa but also protection from allergens, pathogens, and toxins [1, 2]. The gastrointestinal tract (GI) and its associated microbiota is a complex system that allows for the digestion and absorption of critical nutrients. Additionally, the presence of the commensal bacteria leads to the development and regulation of the mucosal immune system [3]. It is believed that 60% of all fecal matter mass in humans consists of bacteria and that there are between 1010 and 1012 colony-forming units per gram of intestinal content in the colon [4]. The intestinal epithelium is a physical and biochemical barrier that seeks to protect mammalian cells from infection and injury from contaminants such as toxins, pathogenic bacteria, commensal bacteria, and even other luminal contents. Specialized intestinal epithelial cells (IECs) are able to sense and respond to these stimuli with appropriate responses such as increasing their barrier function to activation of anti-pathogenic immune mechanisms [3].

The International Scientific Association for Probiotics and Prebiotics (ISAPP) in 2014 agreed on a consensus definition of probiotics based on the previous Food and Agriculture Organization of the United Nations and World Health Organization (WHO) definition. ISAPP defines probiotics as ‘live microorganisms that, when administered in adequate amounts, confer a health benefit on the host” [5]. Probiotics have been used for the treatment of Helicobacter pylori infection, irritable bowl syndrome, and inflammatory bowel disease (ulcerative colitis and Crohn’s disease) in addition to enhancing the immune system of healthy individuals [6, 7, 8, 9, 10, 11, 12].

Though in vivo and in vitro studies suggest that probiotics can be beneficial [1, 2, 13], the exact mechanism(s) remains to be fully explained. Four mechanism are believed to be involved: (a) maintenance of the gut epithelial barrier, (b) competitive exclusion of pathogenic organisms, (c) secretion of antimicrobial products, and (d) regulation of the mucosal immune system in favor of the hosts.

The major defensive mechanism of the gut is the intestinal barrier which maintains epithelial integrity and to protect the host from the environment. In defense of this barrier, there exists the mucous layer, antimicrobial peptides, secretory IgA and the epithelial junction adhesion complex [14]. Disruption of these defense mechanisms allows for the bacteria and food antigens to reach the submucosa, which can induce an inflammatory response potentially leading to the intestinal disorders such as inflammatory bowel disease [15, 16].

1.1 Probiotics

The most common probiotic strains used are Lactobacillus, Bifidobacteria, and the yeast strain Saccharomyces cerevisiae var. boulardii. Lactic acid bacteria and bifidobacteria have been shown to remove heavy metals [17], cyanotoxins [18], and mycotoxin from in vitro aqueous solutions [19, 20].

In regards to maintenance of the gut epithelial barrier, one can upregulate the genes important for this process [21]. Lactobacilli treatment has been shown to affect several genes including E-cadherin and β-catenin that affect adherence cell junctions in a cell culture model. The phosphorylation and abundance of adherence junction proteins including PKCδ [22] has been seen with Lactobacilli treatment. The probiotic Escherichia coli Nissle 1917 strain (EcN1917) can initiate repair of the intestinal barrier after damage by enteropathogenic E. coli by enhancing the expression and redistribution of tight junction proteins of the zonula occludens (ZO-2) and PKC [23, 24]. Treatment with Lactobacillus casei DN-114001 [25] and VSL#3 (an eight combination probiotic strain mixture) [26] also affect the gut barrier.

Another method to promote epithelial barrier function may be to increase mucin production thereby leading to increased barrier function as well as exclusion of pathogens and toxins. There have been contradictory data for both in vitro and in vivo experiments as to whether mucin production occurs in response to probiotic treatment. Some studies have suggested Lactobacillus adhesion is required to increase mucin production, which may not occur in vivo [27, 28]. However, a Lactobacillus acidophilus A4 cell extract has been shown to increase MUC2 expression in HT29 cells independent of attachment [29]. VSL#3 has also been shown to increase expression of MUC2, MUC3, and MUC5AC in HT-29 cells [26]. In vivo studies of mucin production have also been inconsistent. VSL#3 given to mice for 14 days did not show any increase in mucin production or thickness [30] whereas rats given VSL#3 for 7 days have a 60-fold increase in MUC2 expression and secretion [31].

1.2 Prebiotics

Prebiotics and their beneficial effects on human health have been of interest in recent years because of their perceived safety since they are derived from dietary products. The definition of prebiotics has changed somewhat from their initial description in 1995 by Glenn Gibson and Marcel Roberfroid [32]. Today, the general consensus is that “dietary prebiotics” are “selectively fermented ingredients that results in specific changes in the composition and/or activity of the gastrointestinal microbiota, thus conferring benefit(s) upon host health” [33]. There are many types of prebiotics but they can be segregated into the following groups [33]: (1) fructans, (2) galacto-oligosaccharides (GOS), (3) starch and glucose-derived oligosaccharides, (4) other oligosaccharides, and (5) non-carbohydrate oligosaccharides.

Fructans, such as inulin and fructose-oligosaccharides (FOS)/oligofructose, generally have a linear chain of fructose with a β(2 + 1) linkage usually with terminal glucose units with a β(2 + 1) linkage with variable degrees of polymerization (DP) [33, 34, 35, 36]. GOS is the product of lactose extension that can be classified into two subgroups: (i) excess galactose at C3, C4 or C6 and (ii) derived from enzymatic trans-glycosylation [33]. The product of the enzymatic trans-glycosylation is a mixture of tri-to pentasaccharides with galactose known as trans-galacto-oligosaccharides (TOS) [37, 38]. In addition, there are GOSs derived from lactulose, an isomer of lactose, as well as raffinose family of oligosaccharides (RFO) [33, 37]. Starch that is resistant to the upper gut digestion is known as resistant starch (RS) and is considered a prebiotic along with polydextrose (glucose-derived oligosaccharide) [39, 40]. Pectin derived oligosaccharides (POS) are derived from an extension of galacturonic acid or rhamnose [33]. The carboxyl groups of POS can be modified with methyl esterification as well as acetylated at C2 or C3. Additionally, many different types of sugars (i.e. arabinose, galactose, and xylose) or ferulic acid can be linked to the side chains of POS [41, 42]. Though most of the accepted compounds defined as prebiotics are carbohydrates, there are some non-carbohydrate compounds that are recommended to be classified as prebiotics, i.e. cocoa-derived flavanols [33, 43].

How do prebiotics affect human health? What mechanism(s) are involved? Since prebiotics are derived from dietary products, they provide the metabolic energy for the gut microbiota. This means that they can affect the composition and function of these microorganisms. For example, GOSs can stimulate the growth of Bifidobacteria and Lactobacilli to a high degree while Enterobacteria, Bacteroidetes, and Firmicutes growth levels occurred at a lower level [35]. Cross-feeding, the production of a by-product that can sustain another microorganism, can occur and an example is the degradation of resistant starch by Ruminococcus bromii to provide energy for several other species [44].

In addition to feeding the gut microbiota, the fermentation of prebiotics can generate metabolites such as short chain fatty acids (SCFA) (i.e. lactic acid, butyric acid, and propionic acid) that have dramatic effects not only on the intestinal environment but can affect distant organ sites as well as the immune system. SCFAs decrease the pH of the gut that can alter the composition of the microbiota [45, 46]. A pH unit decrease affects acid sensitive species such as Bacteroides and increases butyrate production by Firmicutes [45]. Butyrate itself has been shown to be important for intestinal cell development [47]. As reviewed in [33], propionate affects the TH2 helper cells, macrophages, and dendritic cells while peptidoglycan stimulates the innate system.


2. Bacterial infections and the disruption of gut homeostasis

Bacterial pathogens are microorganisms that have the ability to cause disease due to their specialized virulence factors or that can arise from a dysbiosis such as from antibiotic treatment that can eliminate the normal healthy flora of the gut leading to opportunistic infections from commensals or normally non-pathogenic organisms.

2.1 Bacterial pathogens, virulence factors, and mechanisms of pathogenesis

Some of the best-known bacterial pathogens are Salmonella enterica, Listeria monocytogenes, Vibrio cholera, Shigella flexneri, Shiga toxin producing E. coli(STEC) (i.e. E. coli 0157:H7), Clostridium difficile, Clostridium perfringens, and Clostridium botulinum. Both Gram-positive and Gram-negative pathogens must develop mechanisms to outcompete the normal gut microbiota, bind/invade cells, avoid detection and killing from the host immune system. Some important pathogen virulence mechanisms consist of specialized secretion systems that encode factors important for all the above steps in pathogenesis. The type III secretion systems (TTSS/T3SS) encoded by some Gram-negative pathogens such as Salmonella, Vibrio, Shigella, Escherichia coli, and Yersinia are well-known examples. Other specialized secretion systems are the T4SS and T6SS. T6SSs are prevalent in both pathogens and commensals suggesting their importance in the intestinal environment [48]. For non-intracellular pathogens, bacterial toxins [i.e., Listeriolysin O (LLO), botulinum neurotoxins (BoNTs), alpha toxin-C. perfringens, TcdA/TcdB-C. difficile] are important virulence factors that can bind to and enter the intestinal epithelium and/or their target cells to effect their functions (i.e. cytotoxicity).

One important growth restriction system on the part of hosts/intestinal flora is the sequestration of iron, which is absolutely required for growth. For example, Salmonella enterica can evade lipocalin-2-mediated growth restriction by producing modified siderophores that cannot be bound by lipocalin-2 [49]. The T4SS and T6SS systems can be utilized for intra-and-inter bacterial species warfare. Bacteroides strains encoding the T6SS have been shown to target sensitive Bacteroides spp. suggesting they limit their competition [50, 51, 52]. Salmonella, Vibrio, and E. coli have also been shown to use T6SS against their competition, the intestinal microbiota [53, 54, 55].

2.2 The mammalian host response to bacterial infections

Probiotic strains have been shown to induce the release of defensins, small peptides/proteins active against bacteria, fungi, and viruses but also are able to stabilize the gut barrier from epithelial cells. Host cells are able to mount as a first line of defense against pathogens increased production of antimicrobial proteins (AMPs) such as α- and β-defensins, cathelicidins, C-type lectins and ribonucleases. Many of these proteins disrupt the cell wall structures of the bacterial membrane either through enzymatic (i.e. lysozyme, phospholipase A2) or non-enzymatic mechanisms (i.e. pore formation by defensins and cathelicidins) [56, 57, 58].

The effect of commensal and probiotic bacteria on the host immune system is complex and not fully understood. It is believed that the effect of probiotic bacteria in modulating the immune system lies with its potential interactions with the host innate immune system by activating pattern recognition receptors (PRRs) that recognize common structures called pathogen-associated molecular patterns (PAMPs) shared by the vast majority of pathogens. Of note are the potential interactions with toll-like receptors (TLRs), extracellular C-type lectin receptors (CLRs), and intracellular nucleotide-binding oligomerization domain-containing protein (NOD)-like receptors (NLRs) that recognize PAMPs such as lipopolysaccharide (LPS), peptidoglycan, lipoprotein, flagellin, and CpGDNA. Activation of these receptor complexes will activate multiple downstream signaling pathways that may induce a pro- or anti-inflammatory response. Dysregulation of the pro-inflammatory response has been implicated in Crohn’s disease with human intestinal inflammation as well as human autoinflammatory disease [59]. However, expression levels of some of these PRRs are low in immune cells therefore the ability to rapidly induce the expression of the PRRs such as NLRP3 in response to PAMP stimuli are absolutely critical in the defense against potential pathogens [60, 61, 62, 63, 64].


3. Probiotic mechanisms of antagonism against bacterial growth and gene expression

In 1969, Greenberg [65] described the phenomena that Salmonella typhimurium was completely excluded from maggots of blowflies. The term “competitive exclusion” was used to define the scenario in which one species of bacteria more vigorously competes for the receptor sites in the intestinal tract than another species. There are a variety of mechanisms used by one bacterial species to exclude or reduce the growth of another species such as creation of a hostile environment, blocking available receptor sites, production and secretion of antimicrobial products and specific metabolites, and competitive depletion of essential nutrients [66].

Lactobacilli and bifidobacteria have been shown to inhibit a broad range of pathogens including E. coli, Salmonella, Helicobacter pylori, Listeria monocytogenes and rotavirus [6, 67, 68, 69, 70, 71, 72, 73]. Competition for host cell surface receptors by some probiotics has been successful against some enteropathogens [74, 75, 76]. L. rhamnosus can prevent enterohemorrhagic E. coli (EHEC) internalization [77]. Probiotic inhibition of pathogen binding to host cells relies heavily on steric hindrance [78].

Lactobacilli have been shown to produce bacteriocins that are active against some foodborne pathogens [79]. Additionally production of various metabolites and low molecular weight products by probiotics have been shown to have antimicrobial and antifungal properties such as low molecular weight species, deconjugated bile acids, and cyclic dipeptides among others [80, 81, 82, 83, 84, 85]. Enterococcus faecium BGPAS1–3 has been shown to produce a cell wall product that has an anti-listerial effect, prevents tight junction disruption, as well as modulating the TLR2/TLR4 immune response to Listeria monocytogenes ATCC19111 [86]. L. plantarum ATCC 8014 has recently been shown to have in vitro antimicrobial activity against C. butryicum ATCC 860, C. difficile ATCC 9689, and C. perfringens ATCC 12924 suggesting that this probiotic strain may have therapeutic potential [87].

The production of antimicrobial substances such as lactic and acetic acid is one example of probiotics making the host environment hostile for pathogens. Lactobacillus co-cultivation with E. coli O157:H7 in broth culture produced organic acids which lead to a decrease in both pH and stx2A expression [88]. Low pH also prevented the induction of Stx prophage [89]. Mice given Lactobacillus reuteri with E. coli O157:H7 had decreased intestinal pathogen count, weight gain, and less kidney damage than controls [90]. The presence of probiotics in cattle feed reduced the amount E. coli O157:H7 seen in cattle [91]. Bifidobacterium strains decrease STEC and in vivo expression of Shiga toxin due to low pH and production of acetate [92, 93]. Pre-treatment with live Lactobacilli before Salmonella enterica Javiana infection in a tissue culture model showed decrease expression of virulence genes, less cytotoxicity, and reduced host production of inflammatory cytokines [94].


4. Probiotics and inhibition of bacterial toxins

Clostridium botulinum is an ubiquitous, gram-positive, anaerobic spore-forming organism that is the causative agent of botulinum. The botulinum neurotoxins are one of the most lethal toxins known to mankind with a parenteral lethal dosage of 0.1–1 ng/kg and an oral dose of 1 μg/kg. Due to this high toxicity and potential for bioterrorism, botulinum neurotoxins (BoNTs) are considered Tier 1 category Select Agents by the Centers for Disease Control and Prevention (CDC). BoNTs are a public health and safety threat in the form of foodborne, wound, and infant botulism.

In order to cause disease for foodborne botulism, BoNTs must first be able to survive in the intestinal lumen, bind to and translocate through the intestinal epithelium to reach the bloodstream [95]. Once in the bloodstream, BoNTs bind to peripheral cholinergic neurons to cleave SNAREs and block exocytosis of neurotransmitters hence leading to flaccid muscle paralysis. Similar to other classic A-B chain toxins, the heavy chain (B chain) of BoNTs bind to carbohydrate and protein receptors on their target cell while the light chain (A chain) has the enzymatic function. Therefore, there are two potential therapeutic pathways to block BoNT intoxication: (1) blocking binding/translocation at the intestinal epithelium/target cells and (2) degradation or inactivation of the toxin It has been shown that pre-treatment with probiotics (Saccharomyces cerevisiae var. boulardii, Lactobacillus acidophilus, Lactobacillus rhamnosus LGG, and Lactobacillus reuteri) was able to block toxin binding to cells in an in vitro Caco-2 cell culture model and that the mechanism most likely used by the probiotics was steric hindrance of binding to host receptors [96].

Another mechanism to inactivate bacterial toxins would to be to subject them to proteolysis thus rendering them inactive. S. boulardii has been shown to produce a 54-KDa protease that is able to cleave and inactivate the two main C. difficile toxins, TcdA and TcdB [97] in a HT-29 colonic cell model. Whether or not this occurs in any significant degree in human infection is still unclear.


5. Probiotics and/or prebiotics as therapeutics to combat gastrointestinal diseases and bacterial infections

Studies in using probiotics as a treatment for a diverse set of diseases ranging from colorectal cancer, traditional gastrointestinal diseases (i.e. IBS/IBD/RCDI), as well as non-gastrointestinal diseases such as arthritis, autism, multiple sclerosis, and Parkinson’s among others [99] has been undertaken. In this chapter, we will focus mainly on the effect probiotic and/prebiotic treatments on gastrointestinal diseases.

The therapeutic potential of prebiotics has been investigated for some gastrointestinal disorders. Irritable bowel syndrome (IBS) is a gastrointestinal disease characterized by chronic pain and altered bowel movements with no clear cause. Crohn’s disease, a chronic relapsing inflammatory bowel disease (IBD), can affect any part of the gastrointestinal tract. For both conditions, it has been speculated that a shift in the gut microbiota population lays at the foundation of these diseases. It has been shown that the Bifidobacteria, Faecalibacterium prausnitzii, Bacteroides to Firmicutes population ratio were decreased [100, 101].

Therefore, prebiotics were hypothesized as a potential therapeutic because of its known properties to stimulate the growth of beneficial bacteria. In regards to IBS, the results were unclear for 4 clinical trials. Two clinical trials had no improvement [102, 103] whereas two studies using FOS and GOS showed an improvement in IBS symptoms [104, 105]. In the case of Crohn’s disease, one study showed improvement [106] while two did not [107, 108]. As reviewed in [109], their analysis of available studies indicated that generally, the conclusions were supportive of probiotic treatment for IBS, however, the exact beneficial strains to be used were unclear. The caveats from these studies were the variabilities in the type of prebiotic(s) used, the dosage, time of supplementation, and patient disease stage. As has been used in the treatment of recurrent C. difficile infection (RCDI), fecal microbiota transplantation (FMT) has also been used with success in the treatment of IBS and IBD (i.e. Crohn’s disease) [99].

The recurrent infection in humans with recurrent Clostridium difficile infection (RCDI) in hospitalized patients treated with antibiotics is a severe problem. Studies have successfully used the transfer of healthy gut microbiota to the infected individuals as a treatment [110, 111]. As reviewed in [99], an amazing success rate of ≈92% of RCDI patients was found after FMT therapy.

Another area of medical use that prebiotics may impact is on the health of preterm neonates. These babies are at significant risk of developing the severe gastrointestinal condition necrotizing enterocolitis (NEC), a life-threatening condition. Studies have shown that FOS and GOS prebiotics can help prime the growth of gut bacteria such as Bifidobacteria and reduce pathogenic organisms in preterm babies [112, 113, 114] thereby preventing NEC. Additionally, SCFAs from prebiotic fermentation enhances both gastric emptying and bowel motility [115, 116]. A systemic analysis of four randomized controlled trials showed elevated concentrations of fecal Bifidobacteria if babies were given FOS, GOS, or their mixture, but there was no significant risk reduction or progression to NEC [117]. In a review of several studies regarding probiotics and their effectiveness in preventing necrotizing enterocolitis (NEC) in preterm infants [13, 118], the authors concluded a beneficial effect of using probiotics but this benefit decreased over time. However, since the studies varied in age, doses, and duration of treatment, this observation has probably very little effect on NEC.

The successful use of probiotics in treating acute infectious diarrhea (AID) in children is well documented and accepted treatment therapy [119]. It has beneficial effects for children at risk (i.e. hospital acquired diarrhea) and should be used early after onset of symptoms. Its usage, however, in healthy populations as a preventive measure to prevent diarrhea in day care centers and communities is currently unknown and not advised.

It has been shown that E. coli Nissle 1917 can outcompete Salmonella for iron leading to reduced Salmonella colonization and inflammation [120]. E. coli Nissle 1917 also can prevent L. monocytogenes entry into cell lines [121]. Probiotic treatment against Listeria infections has best been shown in the poultry industry. Competitive exclusion (CE) cultures have been developed and used successfully. Pre-treatment with CE prevented the expansion of Listeria monocytogenes in young chickens [122].

The development of synthetic oligosaccharide-based mimics such as Synsorb (inert silica particles-linked to synthetic oligosaccharides) have been developed against a variety of toxins including: Stx1/2-Gb3, Stx2e-Gb4, Ctx-GM1, LT-GM1, epsilon toxin–GM2, TcdA-Lewis X and Lewis Y, botulinum neurotoxin- GD1a, GT1b, E. coli K88 ad fimbriae-nLc4, E. coli P pili- Gb3 and Gb4 [98]. However, the results for these synthetic oligosaccharide conjugates have been mixed. Synsorb-PK was designed as a mimic for Gb3, receptor for Stx1/2, to prevent intoxication with Shigella and STEC strains but failed to prevent the progression of children to hemolytic uremic syndrome (HUS) in a clinical trial [123]. However, there could be at least two reasons as to the failure of this compound, (1) treatment given late in the onset of disease and (2) potential steric hindrance of the size of the compound. Synsorb-90 was developed in the treatment of severe colitis due to C. difficile infection. This compound was able to bind TcdA in vitro as well as decrease toxin-mediated fluid secretion in a rat-ileal loop model [124]. However, phase III clinical trials for Synsorb-90 was abandoned after promising results from both phase I and phase II trials so we still do not know its efficacy [125].

STEC gastroenteritis has not been traditionally treated with probiotics/FMT as has been seen with acute gastroenteritis and RCDI. There has been a plethora of evidence suggesting the role of probiotic strains in having an antimicrobial effect on STEC but the effects were dependent on the strain(s) used as reviewed in [126]. Additionally, recombinant receptor mimics have been targeted against STEC [98].

In the three studies that mimicked human digestive conditions, S. cerevisiae CNCM I-3856 was implicated in having antagonistic effects on STEC including downregulating Stx expression and how the resident microbiota regulates infectivity [126, 127, 128, 129].

Though there have been many successful and safe uses of probiotics for treatment of multiple conditions, there have been reported side effects linked to their usage especially in vulnerable populations [130]. As reviewed in [131], there has been movement toward using extracellular vesicles (EVs) derived from probiotic strains (both Gram-negative and Gram-positive) to deliver the same beneficial effects as from using the probiotic strains themselves. There are many different pathways that EVs utilize including bacteria-bacteria communication, affecting host microbial interactions, host immune system, increasing tight junction function, and decreasing inflammatory responses from TLR signaling [131].


6. Future works and perspectives

It has been shown that the development of gastrointestinal disease is due to an imbalance in the host response (physical, commensal microbiota, adaptive/innate immune systems) to bacterial infections. There has been an increasing accumulation of evidence (in vitro, in silico, and some in vivo) supporting the key role that the resident microbiota in the gut plays in mitigating bacterial infections as well as metabolic and physical diseases. There has been development of novel therapies all designed to replace/regenerate the lost beneficial commensal strains in a variety of diseases such as IBS, IBD, acute gastroenteritis, NEC, RCDI, etc. There has been tremendous success in the treatment of RCDI, IBS, and IBD using FMT therapy. However, it is still unclear from all the evidence that giving probiotics and/or prebiotics will mitigate all gastrointestinal diseases [13]. The beneficial effects of a probiotic(s)/prebiotic mixture is utterly dependent on many factors including: time of dosage in relation to disease, probiotic strains used, prebiotics given, dosage, time of treatment, pre, post, and the pre-existing health and/or the microbiota of the host. Additionally, the clinical trials should also be developed with statistical power to clearly answer the question at hand.



This work was funded by the United States Department of Agriculture, Agricultural Research Service, National Program project NP108, CRIS 2030-42000-049-00D.


Conflict of interest

The authors have no conflict of interest.


  1. 1. Rao RK, Samak G. Protection and restitution of gut barrier by probiotics: Nutritional and clinical implications. Current Nutrition & Food Science. 2013;9(2):99-107
  2. 2. Bermudez-Brito M, Plaza-Diaz J, Munoz-Quezada S, Gomez-Llorente C, Gil A. Probiotic mechanisms of action. Annals of Nutrition & Metabolism. 2012;61(2):160-174
  3. 3. Peterson LW, Artis D. Intestinal epithelial cells: Regulators of barrier function and immune homeostasis. Nature Reviews. Immunology. 2014;14(3):141-153
  4. 4. Stephen AM, Cummings JH. The microbial contribution to human faecal mass. Journal of Medical Microbiology. 1980;13(1):45-56
  5. 5. Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, et al. Expert consensus document. The international scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nature Reviews. Gastroenterology & Hepatology. 2014;11(8):506-514
  6. 6. Myllyluoma E, Veijola L, Ahlroos T, Tynkkynen S, Kankuri E, Vapaatalo H, et al. Probiotic supplementation improves tolerance to Helicobacter pylori eradication therapy--a placebo-controlled, double-blind randomized pilot study. Alimentary Pharmacology & Therapeutics. 2005;21(10):1263-1272
  7. 7. Kajander K, Hatakka K, Poussa T, Farkkila M, Korpela R. A probiotic mixture alleviates symptoms in irritable bowel syndrome patients: A controlled 6-month intervention. Alimentary Pharmacology & Therapeutics. 2005;22(5):387-394
  8. 8. Olivares M, Diaz-Ropero MA, Gomez N, Lara-Villoslada F, Sierra S, Maldonado JA, et al. Oral administration of two probiotic strains, Lactobacillus gasseri CECT5714 and Lactobacillus coryniformis CECT5711, enhances the intestinal function of healthy adults. International Journal of Food Microbiology. 2006;107(2):104-111
  9. 9. Olivares M, Diaz-Ropero MP, Gomez N, Lara-Villoslada F, Sierra S, Maldonado JA, et al. The consumption of two new probiotic strains, Lactobacillus gasseri CECT 5714 and Lactobacillus coryniformis CECT 5711, boosts the immune system of healthy humans. International Microbiology. 2006;9(1):47-52
  10. 10. Kim HJ, Vazquez Roque MI, Camilleri M, Stephens D, Burton DD, Baxter K, et al. A randomized controlled trial of a probiotic combination VSL# 3 and placebo in irritable bowel syndrome with bloating. Neurogastroenterology and Motility. 2005;17(5):687-696
  11. 11. Derikx LA, Dieleman LA, Hoentjen F. Probiotics and prebiotics in ulcerative colitis. Best Practice & Research. Clinical Gastroenterology. 2016;30(1):55-71
  12. 12. Bibiloni R, Fedorak RN, Tannock GW, Madsen KL, Gionchetti P, Campieri M, et al. VSL#3 probiotic-mixture induces remission in patients with active ulcerative colitis. The American Journal of Gastroenterology. 2005;100(7):1539-1546
  13. 13. Suez J, Zmora N, Segal E, Elinav E. The pros, cons, and many unknowns of probiotics. Nature Medicine. 2019;25(5):716-729
  14. 14. Ohland CL, Macnaughton WK. Probiotic bacteria and intestinal epithelial barrier function. American Journal of Physiology. Gastrointestinal and Liver Physiology. 2010;298(6):G807-G819
  15. 15. Hooper LV, Wong MH, Thelin A, Hansson L, Falk PG, Gordon JI. Molecular analysis of commensal host-microbial relationships in the intestine. Science. 2001;291(5505):881-884
  16. 16. Hooper LV, Stappenbeck TS, Hong CV, Gordon JI. Angiogenins: A new class of microbicidal proteins involved in innate immunity. Nature Immunology. 2003;4(3):269-273
  17. 17. Halttunen T, Collado MC, El-Nezami H, Meriluoto J, Salminen S. Combining strains of lactic acid bacteria may reduce their toxin and heavy metal removal efficiency from aqueous solution. Letters in Applied Microbiology. 2008;46(2):160-165
  18. 18. Nybom SM, Salminen SJ, Meriluoto JA. Specific strains of probiotic bacteria are efficient in removal of several different cyanobacterial toxins from solution. Toxicon. 2008;52(2):214-220
  19. 19. El-Nezami H, Kankaanpaa P, Salminen S, Ahokas J. Ability of dairy strains of lactic acid bacteria to bind a common food carcinogen, aflatoxin B1. Food and Chemical Toxicology. 1998;36(4):321-326
  20. 20. Oatley JT, Rarick MD, Ji GE, Linz JE. Binding of aflatoxin B1 to bifidobacteria in vitro. Journal of Food Protection. 2000;63(8):1133-1136
  21. 21. Anderson RC, Cookson AL, McNabb WC, Kelly WJ, Roy NC. Lactobacillus plantarum DSM 2648 is a potential probiotic that enhances intestinal barrier function. FEMS Microbiology Letters. 2010;309(2):184-192
  22. 22. Hummel S, Veltman K, Cichon C, Sonnenborn U, Schmidt MA. Differential targeting of the E-cadherin/beta-catenin complex by gram-positive probiotic lactobacilli improves epithelial barrier function. Applied and Environmental Microbiology. 2012;78(4):1140-1147
  23. 23. Zyrek AA, Cichon C, Helms S, Enders C, Sonnenborn U, Schmidt MA. Molecular mechanisms underlying the probiotic effects of Escherichia coli Nissle 1917 involve ZO-2 and PKCzeta redistribution resulting in tight junction and epithelial barrier repair. Cellular Microbiology. 2007;9(3):804-816
  24. 24. Stetinova V, Smetanova L, Kvetina J, Svoboda Z, Zidek Z, Tlaskalova-Hogenova H. Caco-2 cell monolayer integrity and effect of probiotic Escherichia coli Nissle 1917 components. Neuro Endocrinology Letters. 2010;31(Suppl 2):51-56
  25. 25. Parassol N, Freitas M, Thoreux K, Dalmasso G, Bourdet-Sicard R, Rampal P. Lactobacillus casei DN-114 001 inhibits the increase in paracellular permeability of enteropathogenic Escherichia coli-infected T84 cells. Research in Microbiology. 2005;156(2):256-262
  26. 26. Otte JM, Podolsky DK. Functional modulation of enterocytes by gram-positive and gram-negative microorganisms. American Journal of Physiology. Gastrointestinal and Liver Physiology. 2004;286(4):G613-G626
  27. 27. Mattar AF, Teitelbaum DH, Drongowski RA, Yongyi F, Harmon CM, Coran AG. Probiotics up-regulate MUC-2 mucin gene expression in a Caco-2 cell-culture model. Pediatric Surgery International. 2002;18(7):586-590
  28. 28. Mack DR, Ahrne S, Hyde L, Wei S, Hollingsworth MA. Extracellular MUC3 mucin secretion follows adherence of Lactobacillus strains to intestinal epithelial cells in vitro. Gut. 2003;52(6):827-833
  29. 29. Kim Y, Kim SH, Whang KY, Kim YJ, Oh S. Inhibition of Escherichia coli O157:H7 attachment by interactions between lactic acid bacteria and intestinal epithelial cells. Journal of Microbiology and Biotechnology. 2008;18(7):1278-1285
  30. 30. Gaudier E, Michel C, Segain JP, Cherbut C, Hoebler C. The VSL# 3 probiotic mixture modifies microflora but does not heal chronic dextran-sodium sulfate-induced colitis or reinforce the mucus barrier in mice. The Journal of Nutrition. 2005;135(12):2753-2761
  31. 31. Caballero-Franco C, Keller K, De Simone C, Chadee K. The VSL#3 probiotic formula induces mucin gene expression and secretion in colonic epithelial cells. American Journal of Physiology. Gastrointestinal and Liver Physiology. 2007;292(1):G315-G322
  32. 32. Gibson GR, Roberfroid MB. Dietary modulation of the human colonic microbiota: Introducing the concept of prebiotics. The Journal of Nutrition. 1995;125(6):1401-1412
  33. 33. Davani-Davari D, Negahdaripour M, Karimzadeh I, Seifan M, Mohkam M, Masoumi SJ, et al. Prebiotics: Definition, types, sources, mechanisms, and clinical applications. Food. 2019;8(3). Article ID: 92
  34. 34. Monsan P, Paul F. Enzymatic synthesis of oligosaccharides. FEMS Microbiology Reviews. 1995;16(2-3):187-192
  35. 35. Louis P, Flint HJ, Michel C. How to manipulate the microbiota: Prebiotics. Advances in Experimental Medicine and Biology. 2016;902:119-142
  36. 36. Scott KP, Martin JC, Duncan SH, Flint HJ. Prebiotic stimulation of human colonic butyrate-producing bacteria and bifidobacteria, in vitro. FEMS Microbiology Ecology. 2014;87(1):30-40
  37. 37. Roberfroid M, Gibson GR, Hoyles L, McCartney AL, Rastall R, Rowland I, et al. Prebiotic effects: Metabolic and health benefits. The British Journal of Nutrition. 2010;104(Suppl 2):S1-S63
  38. 38. Macfarlane GT, Steed H, Macfarlane S. Bacterial metabolism and health-related effects of galacto-oligosaccharides and other prebiotics. Journal of Applied Microbiology. 2008;104(2):305-344
  39. 39. Fuentes-Zaragoza E, Sánchez-Zapata E, Sendra E, Sayas E, Navarro C, Fernández-López J, et al. Resistant starch as prebiotic: A review. Starch - Stärke. 2011;63(7):406-415
  40. 40. Costabile A, Fava F, Röytiö H, Forssten SD, Olli K, Klievink J, et al. Impact of polydextrose on the faecal microbiota: A double-blind, crossover, placebo-controlled feeding study in healthy human subjects. The British Journal of Nutrition. 2012;108(3):471-481
  41. 41. Yoo H-D, Kim D, Paek S-H. Plant cell wall polysaccharides as potential resources for the development of novel prebiotics. Biomolecules & Therapeutics (Seoul). 2012;20(4):371-379
  42. 42. Gullón B, Gómez B, Martínez-Sabajanes M, Yáñez R, Parajó JC, Alonso JL. Pectic oligosaccharides: Manufacture and functional properties. Trends in Food Science and Technology. 2013;30(2):153-161
  43. 43. Tzounis X, Rodriguez-Mateos A, Vulevic J, Gibson GR, Kwik-Uribe C, Spencer JPE. Prebiotic evaluation of cocoa-derived flavanols in healthy humans by using a randomized, controlled, double-blind, crossover intervention study. The American Journal of Clinical Nutrition. 2010;93(1):62-72
  44. 44. Ze X, Duncan SH, Louis P, Flint HJ. Ruminococcus bromii is a keystone species for the degradation of resistant starch in the human colon. The ISME Journal. 2012;6(8):1535-1543
  45. 45. Walker AW, Duncan SH, McWilliam Leitch EC, Child MW, Flint HJ. pH and peptide supply can radically alter bacterial populations and short-chain fatty acid ratios within microbial communities from the human colon. Applied and Environmental Microbiology. 2005;71(7):3692-3700
  46. 46. Duncan SH, Louis P, Thomson JM, Flint HJ. The role of pH in determining the species composition of the human colonic microbiota. Environmental Microbiology. 2009;11(8):2112-2122
  47. 47. Hamer HM, Jonkers D, Venema K, Vanhoutvin S, Troost FJ, Brummer RJ. Review article: The role of butyrate on colonic function. Alimentary Pharmacology & Therapeutics. 2008;27(2):104-119
  48. 48. Rangan KJ, Hang HC. Biochemical mechanisms of pathogen restriction by intestinal bacteria. Trends in Biochemical Sciences. 2017;42(11):887-898
  49. 49. Raffatellu M, George MD, Akiyama Y, Hornsby MJ, Nuccio SP, Paixao TA, et al. Lipocalin-2 resistance confers an advantage to Salmonella enterica serotype Typhimurium for growth and survival in the inflamed intestine. Cell Host & Microbe. 2009;5(5):476-486
  50. 50. Wexler AG, Bao Y, Whitney JC, Bobay LM, Xavier JB, Schofield WB, et al. Human symbionts inject and neutralize antibacterial toxins to persist in the gut. Proceedings of the National Academy of Sciences of the United States of America. 2016;113(13):3639-3644
  51. 51. Russell AB, Wexler AG, Harding BN, Whitney JC, Bohn AJ, Goo YA, et al. A type VI secretion-related pathway in Bacteroidetes mediates interbacterial antagonism. Cell Host & Microbe. 2014;16(2):227-236
  52. 52. Chatzidaki-Livanis M, Geva-Zatorsky N, Comstock LE. Bacteroides fragilis type VI secretion systems use novel effector and immunity proteins to antagonize human gut Bacteroidales species. Proceedings of the National Academy of Sciences of the United States of America. 2016;113(13):3627-3632
  53. 53. Sana TG, Flaugnatti N, Lugo KA, Lam LH, Jacobson A, Baylot V, et al. Salmonella typhimurium utilizes a T6SS-mediated antibacterial weapon to establish in the host gut. Proceedings of the National Academy of Sciences of the United States of America. 2016;113(34):E5044-E5051
  54. 54. MacIntyre DL, Miyata ST, Kitaoka M, Pukatzki S. The Vibrio cholerae type VI secretion system displays antimicrobial properties. Proceedings of the National Academy of Sciences of the United States of America. 2010;107(45):19520-19524
  55. 55. Fu Y, Waldor MK, Mekalanos JJ. Tn-Seq analysis of Vibrio cholerae intestinal colonization reveals a role for T6SS-mediated antibacterial activity in the host. Cell Host & Microbe. 2013;14(6):652-663
  56. 56. Muller CA, Autenrieth IB, Peschel A. Innate defenses of the intestinal epithelial barrier. Cellular and Molecular Life Sciences. 2005;62(12):1297-1307
  57. 57. Kagan BL, Selsted ME, Ganz T, Lehrer RI. Antimicrobial defensin peptides form voltage-dependent ion-permeable channels in planar lipid bilayer membranes. Proceedings of the National Academy of Sciences of the United States of America. 1990;87(1):210-214
  58. 58. Bals R, Wilson JM. Cathelicidins–A family of multifunctional antimicrobial peptides. Cellular and Molecular Life Sciences. 2003;60(4):711-720
  59. 59. Hirota SA, Ng J, Lueng A, Khajah M, Parhar K, Li Y, et al. NLRP3 inflammasome plays a key role in the regulation of intestinal homeostasis. Inflammatory Bowel Diseases. 2011;17(6):1359-1372
  60. 60. Bauernfeind FG, Horvath G, Stutz A, Alnemri ES, MacDonald K, Speert D, et al. Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression. Journal of Immunology. 2009;183(2):787-791
  61. 61. Bauernfeind F, Ablasser A, Kim S, Bartok E, Hornung V. An unexpected role for RNA in the recognition of DNA by the innate immune system. RNA Biology. 2010;7(2):151-157
  62. 62. Kim S, Bauernfeind F, Ablasser A, Hartmann G, Fitzgerald KA, Latz E, et al. Listeria monocytogenes is sensed by the NLRP3 and AIM2 inflammasome. European Journal of Immunology. 2010;40(6):1545-1551
  63. 63. Meylan E, Tschopp J, Karin M. Intracellular pattern recognition receptors in the host response. Nature. 2006;442(7098):39-44
  64. 64. Martinon F, Mayor A, Tschopp J. The inflammasomes: Guardians of the body. Annual Review of Immunology. 2009;27:229-265
  65. 65. Greenberg B. Salmonella suppression by known populations of bacteria in flies. Journal of Bacteriology. 1969;99(3):629-635
  66. 66. Rolfe RD. Population dynamics of the intestinal tract. In: Blankenship LC, editor. Colonization control of human bacterial enteropathogens in poultry. San Diego, CA, USA: Academic Press Inc; 1991
  67. 67. Chenoll E, Casinos B, Bataller E, Astals P, Echevarria J, Iglesias JR, et al. Novel probiotic Bifidobacterium bifidum CECT 7366 strain active against the pathogenic bacterium Helicobacter pylori. Applied and Environmental Microbiology. 2011;77(4):1335-1343
  68. 68. Sgouras D, Maragkoudakis P, Petraki K, Martinez-Gonzalez B, Eriotou E, Michopoulos S, et al. In vitro and in vivo inhibition of Helicobacter pylori by Lactobacillus casei strain Shirota. Applied and Environmental Microbiology. 2004;70(1):518-526
  69. 69. Todoriki K, Mukai T, Sato S, Toba T. Inhibition of adhesion of food-borne pathogens to Caco-2 cells by Lactobacillus strains. Journal of Applied Microbiology. 2001;91(1):154-159
  70. 70. Chu H, Kang S, Ha S, Cho K, Park SM, Han KH, et al. Lactobacillus acidophilus expressing recombinant K99 adhesive fimbriae has an inhibitory effect on adhesion of enterotoxigenic Escherichia coli. Microbiology and Immunology. 2005;49(11):941-948
  71. 71. Tsai CC, Lin PP, Hsieh YM. Three Lactobacillus strains from healthy infant stool inhibit enterotoxigenic Escherichia coli grown in vitro. Anaerobe. 2008;14(2):61-67
  72. 72. Munoz JA, Chenoll E, Casinos B, Bataller E, Ramon D, Genoves S, et al. Novel probiotic Bifidobacterium longum subsp. infantis CECT 7210 strain active against rotavirus infections. Applied and Environmental Microbiology. 2011;77(24):8775-8783
  73. 73. Nakamura S, Kuda T, An C, Kanno T, Takahashi H, Kimura B. Inhibitory effects of Leuconostoc mesenteroides 1RM3 isolated from narezushi, a fermented fish with rice, on Listeria monocytogenes infection to Caco-2 cells and A/J mice. Anaerobe. 2012;18(1):19-24
  74. 74. Neeser JR, Granato D, Rouvet M, Servin A, Teneberg S, Karlsson KA. Lactobacillus johnsonii La1 shares carbohydrate-binding specificities with several enteropathogenic bacteria. Glycobiology. 2000;10(11):1193-1199
  75. 75. Fujiwara S, Hashiba H, Hirota T, Forstner JF. Inhibition of the binding of enterotoxigenic Escherichia coli Pb176 to human intestinal epithelial cell line HCT-8 by an extracellular protein fraction containing BIF of Bifidobacterium longum SBT2928: Suggestive evidence of blocking of the binding receptor gangliotetraosylceramide on the cell surface. International Journal of Food Microbiology. 2001;67(1-2):97-106
  76. 76. Mukai T, Asasaka T, Sato E, Mori K, Matsumoto M, Ohori H. Inhibition of binding of Helicobacter pylori to the glycolipid receptors by probiotic Lactobacillus reuteri. FEMS Immunology and Medical Microbiology. 2002;32(2):105-110
  77. 77. Hirano J, Yoshida T, Sugiyama T, Koide N, Mori I, Yokochi T. The effect of Lactobacillus rhamnosus on enterohemorrhagic Escherichia coli infection of human intestinal cells in vitro. Microbiology and Immunology. 2003;47(6):405-409
  78. 78. Coconnier MH, Bernet MF, Chauviere G, Servin AL. Adhering heat-killed human Lactobacillus acidophilus, strain LB, inhibits the process of pathogenicity of diarrhoeagenic bacteria in cultured human intestinal cells. Journal of Diarrhoeal Diseases Research. 1993;11(4):235-242
  79. 79. Nielsen DS, Cho GS, Hanak A, Huch M, Franz CM, Arneborg N. The effect of bacteriocin-producing Lactobacillus plantarum strains on the intracellular pH of sessile and planktonic Listeria monocytogenes single cells. International Journal of Food Microbiology. 2010;141(Suppl 1):S53-S59
  80. 80. Lievin V, Peiffer I, Hudault S, Rochat F, Brassart D, Neeser JR, et al. Bifidobacterium strains from resident infant human gastrointestinal microflora exert antimicrobial activity. Gut. 2000;47(5):646-652
  81. 81. Fujiwara S, Hashiba H, Hirota T, Forstner JF. Proteinaceous factor(s) in culture supernatant fluids of bifidobacteria which prevents the binding of enterotoxigenic Escherichia coli to gangliotetraosylceramide. Applied and Environmental Microbiology. 1997;63(2):506-512
  82. 82. Magnusson J, Schnurer J. Lactobacillus coryniformis subsp. coryniformis strain Si3 produces a broad-spectrum proteinaceous antifungal compound. Applied and Environmental Microbiology. 2001;67(1):1-5
  83. 83. Rouse S, Canchaya C, van Sinderen D. Lactobacillus hordei sp. nov., a bacteriocinogenic strain isolated from malted barley. International Journal of Systematic and Evolutionary Microbiology. 2008;58(Pt 9):2013-2017
  84. 84. Rouse S, van Sinderen D. Bioprotective potential of lactic acid bacteria in malting and brewing. Journal of Food Protection. 2008;71(8):1724-1733
  85. 85. Dal Bello F, Clarke CI, Ryan LAM, Ulmer H, Schober TJ, Ström K, et al. Improvement of the quality and shelf life of wheat bread by fermentation with the antifungal strain Lactobacillus plantarum FST 1.7. Journal of Cereal Science. 2007;45(3):309-318
  86. 86. Popovic N, Djokic J, Brdaric E, Dinic M, Terzic-Vidojevic A, Golic N, et al. The influence of heat-killed Enterococcus faecium BGPAS1-3 on the tight junction protein expression and immune function in differentiated Caco-2 cells infected with Listeria monocytogenes ATCC 19111. Frontiers in Microbiology. 2019;10:412
  87. 87. Monteiro C, do Carmo MS, Melo BO, Alves MS, Dos Santos CI, Monteiro SG, et al. In vitro antimicrobial activity and probiotic potential of bifidobacterium and Lactobacillus against species of Clostridium. Nutrients. 2019;11(2):448
  88. 88. Carey CM, Kostrzynska M, Ojha S, Thompson S. The effect of probiotics and organic acids on Shiga-toxin 2 gene expression in enterohemorrhagic Escherichia coli O157:H7. Journal of Microbiological Methods. 2008;73(2):125-132
  89. 89. Imamovic L, Muniesa M. Characterizing RecA-independent induction of Shiga toxin2-encoding phages by EDTA treatment. PLoS One. 2012;7(2):e32393
  90. 90. Eaton KA, Honkala A, Auchtung TA, Britton RA. Probiotic Lactobacillus reuteri ameliorates disease due to enterohemorrhagic Escherichia coli in germfree mice. Infection and Immunity. 2011;79(1):185-191
  91. 91. LeJeune JT, Wetzel AN. Preharvest control of Escherichia coli O157 in cattle. Journal of Animal Science. 2007;85(13 Suppl):E73-E80
  92. 92. Asahara T, Shimizu K, Nomoto K, Hamabata T, Ozawa A, Takeda Y. Probiotic bifidobacteria protect mice from lethal infection with Shiga toxin-producing Escherichia coli O157:H7. Infection and Immunity. 2004;72(4):2240-2247
  93. 93. Fukuda S, Toh H, Hase K, Oshima K, Nakanishi Y, Yoshimura K, et al. Bifidobacteria can protect from enteropathogenic infection through production of acetate. Nature. 2011;469(7331):543-547
  94. 94. Burkholder KM, Fletcher DH, Gileau L, Kandolo A. Lactic acid bacteria decrease Salmonella enterica Javiana virulence and modulate host inflammation during infection of an intestinal epithelial cell line. Pathogens and Disease. 2019;77(3):ftz025
  95. 95. Lam TI, Stanker LH, Lee K, Jin R, Cheng LW. Translocation of botulinum neurotoxin serotype A and associated proteins across the intestinal epithelia. Cellular Microbiology. 2015;17(8):1133-1143
  96. 96. Lam TI, Tam CC, Stanker LH, Cheng LW. Probiotic microorganisms inhibit epithelial cell internalization of botulinum neurotoxin serotype A. Toxins (Basel). 2016;8(12):377
  97. 97. Castagliuolo I, Riegler MF, Valenick L, LaMont JT, Pothoulakis C. Saccharomyces boulardii protease inhibits the effects of Clostridium difficile toxins A and B in human colonic mucosa. Infection and Immunity. 1999;67(1):302-307
  98. 98. Paton AW, Morona R, Paton JC. Designer probiotics for prevention of enteric infections. Nature Reviews. Microbiology. 2006;4(3):193-200
  99. 99. Suchodolski JS, Jergens AE. Recent advances and understanding of using probiotic-based interventions to restore homeostasis of the microbiome for the prevention/therapy of bacterial diseases. Microbiology Spectrum. 2016;4(2):VMBF-0025-2015
  100. 100. Whelan K. Mechanisms and effectiveness of prebiotics in modifying the gastrointestinal microbiota for the management of digestive disorders. The Proceedings of the Nutrition Society. 2013;72(3):288-298
  101. 101. Wilson B, Whelan K. Prebiotic inulin-type fructans and galacto-oligosaccharides: Definition, specificity, function, and application in gastrointestinal disorders. Journal of Gastroenterology and Hepatology. 2017;32(Suppl 1):64-68
  102. 102. Hunter JO, Tuffnell Q , Lee AJ. Controlled trial of oligofructose in the management of irritable bowel syndrome. The Journal of Nutrition. 1999;129(7 Suppl):1451S-1453S
  103. 103. Olesen M, Gudmand-Hoyer E. Efficacy, safety, and tolerability of fructooligosaccharides in the treatment of irritable bowel syndrome. The American Journal of Clinical Nutrition. 2000;72(6):1570-1575
  104. 104. Paineau D, Payen F, Panserieu S, Coulombier G, Sobaszek A, Lartigau I, et al. The effects of regular consumption of short-chain fructo-oligosaccharides on digestive comfort of subjects with minor functional bowel disorders. The British Journal of Nutrition. 2008;99(2):311-318
  105. 105. Silk DB, Davis A, Vulevic J, Tzortzis G, Gibson GR. Clinical trial: The effects of a trans-galactooligosaccharide prebiotic on faecal microbiota and symptoms in irritable bowel syndrome. Alimentary Pharmacology & Therapeutics. 2009;29(5):508-518
  106. 106. Lindsay JO, Whelan K, Stagg AJ, Gobin P, Al-Hassi HO, Rayment N, et al. Clinical, microbiological, and immunological effects of fructo-oligosaccharide in patients with Crohn's disease. Gut. 2006;55(3):348-355
  107. 107. Benjamin JL, Hedin CR, Koutsoumpas A, Ng SC, McCarthy NE, Hart AL, et al. Randomised, double-blind, placebo-controlled trial of fructo-oligosaccharides in active Crohn's disease. Gut. 2011;60(7):923-929
  108. 108. Joossens M, De Preter V, Ballet V, Verbeke K, Rutgeerts P, Vermeire S. Effect of oligofructose-enriched inulin (OF-IN) on bacterial composition and disease activity of patients with Crohn's disease: Results from a double-blinded randomised controlled trial. Gut. 2012;61(6):958
  109. 109. Rodino-Janeiro BK, Vicario M, Alonso-Cotoner C, Pascua-Garcia R, Santos J. A review of microbiota and irritable bowel syndrome: Future in therapies. Advances in Therapy. 2018;35(3):289-310
  110. 110. van Nood E, Dijkgraaf MG, Keller JJ. Duodenal infusion of feces for recurrent Clostridium difficile. The New England Journal of Medicine. 2013;368(22):2145
  111. 111. van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. The New England Journal of Medicine. 2013;368(5):407-415
  112. 112. Knol J, Boehm G, Lidestri M, Negretti F, Jelinek J, Agosti M, et al. Increase of faecal bifidobacteria due to dietary oligosaccharides induces a reduction of clinically relevant pathogen germs in the faeces of formula-fed preterm infants. Acta Paediatrica. Supplement. 2005;94(449):31-33
  113. 113. Boehm G, Lidestri M, Casetta P, Jelinek J, Negretti F, Stahl B, et al. Supplementation of a bovine milk formula with an oligosaccharide mixture increases counts of faecal bifidobacteria in preterm infants. Archives of Disease in Childhood. Fetal and Neonatal Edition. 2002;86(3):F178-F181
  114. 114. Kapiki A, Costalos C, Oikonomidou C, Triantafyllidou A, Loukatou E, Pertrohilou V. The effect of a fructo-oligosaccharide supplemented formula on gut flora of preterm infants. Early Human Development. 2007;83(5):335-339
  115. 115. Indrio F, Riezzo G, Raimondi F, Bisceglia M, Cavallo L, Francavilla R. Effects of probiotic and prebiotic on gastrointestinal motility in newborns. Journal of Physiology and Pharmacology. 2009;60(Suppl 6):27-31
  116. 116. Indrio F, Riezzo G, Raimondi F, Francavilla R, Montagna O, Valenzano ML, et al. Prebiotics improve gastric motility and gastric electrical activity in preterm newborns. Journal of Pediatric Gastroenterology and Nutrition. 2009;49(2):258-261
  117. 117. Srinivasjois R, Rao S, Patole S. Prebiotic supplementation of formula in preterm neonates: A systematic review and meta-analysis of randomised controlled trials. Clinical Nutrition. 2009;28(3):237-242
  118. 118. Patel RM, Underwood MA. Probiotics and necrotizing enterocolitis. Seminars in Pediatric Surgery. 2018;27(1):39-46
  119. 119. Lo Vecchio A, Buccigrossi V, Fedele MC, Guarino A. Acute infectious diarrhea. Advances in Experimental Medicine and Biology. 2019;1125:109-120
  120. 120. Deriu E, Liu JZ, Pezeshki M, Edwards RA, Ochoa RJ, Contreras H, et al. Probiotic bacteria reduce Salmonella typhimurium intestinal colonization by competing for iron. Cell Host & Microbe. 2013;14(1):26-37
  121. 121. Altenhoefer A, Oswald S, Sonnenborn U, Enders C, Schulze J, Hacker J, et al. The probiotic Escherichia coli strain Nissle 1917 interferes with invasion of human intestinal epithelial cells by different enteroinvasive bacterial pathogens. FEMS Immunology and Medical Microbiology. 2004;40(3):223-229
  122. 122. Hume ME, Byrd JA, Stanker LH, Ziprin RL. Reduction of caecal Listeria monocytogenes in Leghorn chicks following treatment with a competitive exclusion culture (PREEMPT). Letters in Applied Microbiology. 1998;26(6):432-436
  123. 123. Trachtman H, Cnaan A, Christen E, Gibbs K, Zhao S, Acheson DW, et al. Effect of an oral Shiga toxin-binding agent on diarrhea-associated hemolytic uremic syndrome in children: A randomized controlled trial. Journal of the American Medical Association. 2003;290(10):1337-1344
  124. 124. Castagliuolo I, LaMont JT, Qiu B, Nikulasson ST, Pothoulakis C. A receptor decoy inhibits the enterotoxic effects of Clostridium difficile toxin A in rat ileum. Gastroenterology. 1996;111(2):433-438
  125. 125. Weiss K. Toxin-binding treatment for Clostridium difficile: A review including reports of studies with tolevamer. International Journal of Antimicrobial Agents. 2009;33(1):4-7
  126. 126. Giordano M, Baldassarre ME, Palmieri V, Torres DD, Carbone V, Santangelo L, et al. Management of STEC gastroenteritis: Is there a role for probiotics? International Journal of Environmental Research and Public Health. 2019;16(9):1649
  127. 127. Etienne-Mesmin L, Livrelli V, Privat M, Denis S, Cardot JM, Alric M, et al. Effect of a new probiotic Saccharomyces cerevisiae strain on survival of Escherichia coli O157:H7 in a dynamic gastrointestinal model. Applied and Environmental Microbiology. 2011;77(3):1127-1131
  128. 128. Thevenot J, Etienne-Mesmin L, Denis S, Chalancon S, Alric M, Livrelli V, et al. Enterohemorrhagic Escherichia coli O157:H7 survival in an in vitro model of the human large intestine and interactions with probiotic yeasts and resident microbiota. Applied and Environmental Microbiology. 2013;79(3):1058-1064
  129. 129. Thevenot J, Cordonnier C, Rougeron A, Le Goff O, Nguyen HT, Denis S, et al. Enterohemorrhagic Escherichia coli infection has donor-dependent effect on human gut microbiota and may be antagonized by probiotic yeast during interaction with Peyer's patches. Applied Microbiology and Biotechnology. 2015;99(21):9097-9110
  130. 130. Marteau P, Shanahan F. Basic aspects and pharmacology of probiotics: An overview of pharmacokinetics, mechanisms of action and side-effects. Best Practice & Research. Clinical Gastroenterology. 2003;17(5):725-740
  131. 131. Molina-Tijeras JA, Galvez J, Rodriguez-Cabezas ME. The immunomodulatory properties of extracellular vesicles derived from probiotics: A novel approach for the management of gastrointestinal diseases. Nutrients. 2019;11(5):1038

Written By

Christina C. Tam, Kirkwood M. Land and Luisa W. Cheng

Submitted: 01 July 2019 Reviewed: 07 August 2019 Published: 03 October 2019