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==Introduction==
The exact mechanisms by which probiotic bacteria are able to impact gastrointestinal (GI) health and interact with various microorganisms can differ between strains. However, in general, the way in which these probiotic bacteria work appears fall into three main categories: through their effects on the gut microbiota and ability to antagonise pathogenic bacteria; by strengthening the intestinal epithelial barrier (gut barrier); and through modulation of the mucosal and systemic immune system.
==Effects of probiotic bacteria on other microorganisms==
*Probiotic bacteria are often acid-producing (e.g. lactic acid) which acts to decrease luminal pH, helping to inhibit the pathogenic organisms that thrive in a more alkaline environment (e.g. E. coli and Salmonella spp.)<ref name=":1">Hemarajata P, Versalovic J. Effects of probiotics on gut microbiota: mechanisms of intestinal immunomodulation and neuromodulation. Therap Adv Gastroenterol 2013; 6(1): 39–51.</ref>
*Probiotic bacteria can have a direct bactericidal effect on pathogenic bacteria.<ref name=":2">Bharti N, Kaur R, Kaur S. Health Benefits Of Probiotic Bacteria As Nutraceuticals. European Journal of Molecular & Clinical Medicine, 2020; 7(7): 4797-4807</ref>
*Through production of antimicrobial substances such as organic acids (lactic acid, acetic acid) and bacteriocins probiotic bacteria can selectively inhibit growth or kill pathogenic bacteria.<ref name=":3">Bermudez-Brito M, Plaza-Díaz J, Muñoz-Quezada S, Gómez-Llorente C, Gil A. Probiotic mechanisms of action. Ann Nutr Metab. 2012; 61(2):160-174</ref><ref name=":4">O'Shea EF, Cotter PD, Stanton C, Ross RP. Production of bioactive substances by intestinal bacteria as a basis for explaining probiotic mechanisms: bacteriocins and conjugated linoleic acid. C Int J Food Microbiol 2012; 152(3):189-205</ref>
*Through competitive exclusion:<ref name=":3"/>
**Strong adherence of probiotic bacteria to luminal mucosal adhesion sites reduces pathogenic bacterial colonisation, whilst also stimulating intestinal immunity
**Probiotic bacteria compete with pathogenic organisms for nutrients and energy
==Effects of probiotic bacteria on the gastrointestinal epithelium==
*Probiotic bacteria can produce certain metabolites (including arginine, glutamine, short-chain fatty acids and conjugated linoleic acids) which have gut-protective properties and can act as an energy source to epithelial cells.<ref name=":4"/>
*Probiotic bacteria can increase mucus production from goblet cells, important for preventing adhesion of pathogenic bacteria to the intestinal epithelium and ensuring normal gut barrier function.<ref name=":5">Hansson GC. Role of mucus layers in gut infection and inflammation. Curr Opin Microbiol 2012; 15(1): 57–62.</ref> Mucins can also act as prebiotics due to their ~90% carbohydrate content, which may be used as an energy source by some probiotic strains.<ref name=":6">Katayama T, Fujita K, Yamamoto K. Novel bifidobacterial glycosides action on sugar chains of mucin glycoproteins. J. Biosci. Bioeng. 2005; 99:457–465</ref>
*Probiotics can promote barrier integrity through enhancement of tight junction formation.<ref name=":7">Resta-Lenert S, Barrett KE. Live probiotics protect intestinal epithelial cells from the effects of infection with enteroinvasive Escherichia coli (EIEC) Gut. 2003;52:988–997 </ref>
==Effects of probiotic bacteria on innate and adaptive immunity==
*Probiotic bacteria can enhance secretory IgA production into the mucus layer; IgA binds to mucins and acts to trap and neutralise pathogens attempting to breach the gut barrier.<ref name=":8">Rautava S, Arvilommi H, Isolaur E. Specific probiotics in enhancing maturation of IgA responses in formula-fed infants. Pediatr. Res. 2006;60:221–224</ref><ref name=":9">Herich R, Levkut M. Lactic acid bacteria, probiotics and immune system. Veterinarni Medicina 2018; 47:169-180.</ref>
*Interactions between probiotics (and resident microflora), intestinal epithelial cells and immune cells can modulate cytokine production, suppressing pro-inflammatory and inducing anti-inflammatory mediators.<ref name=":10">Georgieva M, Georgiev K, Dobromirov P. Probiotics and Immunity. In: Metodiev, K. , editor. Immunopathology and Immunomodulation. London: IntechOpen; 2015 .</ref>
*Probiotics can modulate the functions of both non-specific and specific immune cells (e.g. macrophages, dendritic cells, T-cells, B-cells)<ref name=":10"/><ref name=":11">Isolauri E, Sütas Y, Kankaanpää P, Arvilommi H, Salminen S. Probiotics: effects on immunity. Am J Clin Nutr 2001; 73(2): 444-450</ref>
*Probiotics can enhance the humoral response by increasing circulating antibody responses<ref name=":11"/><ref name=":12">Moreau MC, Hudault S, Bridonneau C. Systemic antibody response to ovalbumin in gnotobiotic C3H/HeJ mice with Bifidobacterium bifidum or Escherichia coli. Microecol Ther 1990; 20:309–12</ref>
As a result of their ability of to support both innate and acquired immunity, as well as their well reported immunomodulatory effects, the use of probiotics in the management of inflammatory, allergic and even neoplastic conditions is receiving more attention. In future, utilising their effects in a more targeted way may be possible; a genetically modified probiotic strain of Lactobacillus lactis can produce a specific anti-inflammatory cytokine (IL-10) designed to target local areas of inflammation within the colon, and has been trialled in people with Crohn’s disease.<ref name=":13">Braat H et al. A phase I trial with transgenic bacteria expressing interleukin-10 in Crohn’s disease. Clin Gastroenterol Hepatol 2006; 4: 754–759</ref> As such, learning more about the mechanisms by which probiotics work could have important therapeutic implications for both human and veterinary patients.
'''Author: Pippa Coupe BVSc, MRCVS Veterinary Product Manager at Protexin Veterinary. Protexin Veterinary is a brand of ADM Protexin Ltd'''
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==References==
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[[Category:Alimentary_System_-_Microbiota|1]]