Probiotics in Health and Disease: A Review of Emerging Evidence of Potential Benefits and Harm

Kebede Abdisa¹, Dagmawit Atalel², Gemechu Berhanu³ and Venkataramana Kandi^4,

¹Department of Veterinary Science, College of Agriculture and Veterinary Science, Ambo University, Ethiopia

²Department of Veterinary Laboratory Technology, Ambo University, Ethiopia

³College of Agriculture and Veterinary Medicine, Dambi Dollo University, Ethiopia

⁴Department of Microbiology, Prathima Institute of Medical Sciences, Karimnagar, Telangana, India

Cite this paper:
Kebede Abdisa, Dagmawit Atalel, Gemechu Berhanu and Venkataramana Kandi. Probiotics in Health and Disease: A Review of Emerging Evidence of Potential Benefits and Harm. American Journal of Microbiological Research. 2022; 10(1):23-33. doi: 10.12691/ajmr-10-1-4

Abstract

Emerging multi-drug resistant pathogens are the main driving force behind the efforts to find an alternative treatment approach such as probiotics. Probiotics are considered living drugs that can reduce the consumption of conventional antibiotics and improve human and animal health. Particularly, bacterial origin probiotics became increasingly popular during the last two decades as a result of the continuously expanding scientific evidence pointing to their beneficial effects on human and animal health. In recent years, there has been an increase in the application of probiotics for the treatment of different infectious diseases and to alleviate the symptoms of many others, including metabolic disorder-related illnesses and cancer. More specifically, diseases and ailments such as diarrhea, urogenital infections, ulcerative colitis, irritable bowel disease, and a host of others have experienced an increase in the use of certain probiotic bacteria. There are several possible mechanisms by which probiotic bacteria can inhibit the effect of other pathogenic microorganisms. This review, therefore, provides an overview of the current status of bacterial probiotics with special emphasis on therapeutic purpose, mechanisms of action, and their selection criteria. It also highlights the emerging pieces of evidence concerning the role of probiotics in health and disease, and the potential limitations and challenges of probiotic development as a novel therapeutic agent.

Keywords:
bacteria drugresistance novel therapeutics probiotics mechanisms of action health diseases

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

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References:

[1]	Heather K. Allen, Julian Trachsel, Torey Looft, and Thomas A. Casey (2014): Finding alternatives to antibiotics. Ann. N.Y. Acad. Sci., 9: 1323.
[2]	Sameer F., Priya M., Surabhi Bishnoi and Amisha Sharma. (2016). Role of Probiotics in human health and disease. Int.J.Curr.Microbiol.App.Sci.5: 328-344.
[3]	McFall Ngai, M. (2013). Animals in a bacterial world, a new imperative for the life sciences. Proc. Natl. Acad. Sci. USA 110: 3229-3236.
[4]	Vishnu HP (2012). Probiotics and oral health, oral health care- Pediatric, Research, Epidemiology, and clinical Practices. INTECH., 1: 195-204.
[5]	Amara A.A. and Shibl A. (2015). Role of Probiotics in health improvement, infection control and disease treatment and management. S. Pharmac. J. 23: 107-114.
[6]	Kavita. R. Pandey & Suresh. R. Naik1 &Babu. V. Vakil. (2015). Probiotics, prebiotics and synbiotics- a review. J F. Sci. Technol. 52: 7577-7587.
[7]	Endeshaw Abatenh, Birhanu Gizaw, Zerihun Tsegay, Genene Tefera, Endegena Aynalem. Health benefits of probiotics. J Bacteriol Infec Dis 2018; 2 (1): 17-27.
[8]	Rout G. K., Jayanta K. P., Sushanto G., Yooheon P., Han S. S. and Gitishree D. (2018). Benefaction of probiotics for human health.J. F. drug analy., 26: 927-939.
[9]	Yusuf N., Syed A. H., Aidil A. H., and Y. S. (2018). Probiotics and Their Potential Preventive and Therapeutic Role for Cancer, High Serum Cholesterol, and Allergic and HIV Diseases. BioMed Res. Intern., 10: 1-17.
[10]	Carlos Ricardo S., Maria R. M. P., Lina M. B. G., Cristine R., Adriane B. P. M. and Vanete Thomaz Soccol. (2014). Current Developments in Probiotics. J. Microb. Biochem. Technol., 7: 11-20.
[11]	Ezema C. Probiotics in animal production: A review. Journal of Veterinary Medicine and Animal Health 2013; 5 (11): 308-316.
[12]	Yousef Nami, Babak Haghshenas, Norhafizah Abdullah, AbolfazlBarzegari, DayangRadiah, Rozita Rosli and Ahmad YariKhosroushahi. (2014). Probiotics or antibiotics: future challenges in medicine. J. Med. Microbio. 64: 137-146.
[13]	Maria K, Dimitrios B and Stavroula K. (2013). Health Benefits of probiotics. ISRN Nutit.5: 1-7.
[14]	Esha A, Pavan B, Guruprasad CN, Savitha N, Pradeep AR. (2011). Probiotics: A novel step towards oral health. Arch. Oral Sci Res; 1: 108-115.
[15]	Paula J.P. Espitia J., Rejane A., Batista, Henriette M.C. Azeredo, and Caio G. (2016). Probiotics and their potential applications in active edible filmsand coatings. F. Res. Internat.90: 42-52.
[16]	Francisco G., Mary E. S., Rami E., Richard F., Alfred G., James G., Pedro Kaufmann, TarkanKarakan, Aamir G. Khan, Nayoung Kim, Juan Andrés De Paula, Balakrishnan Ramakrishna, Fergus Shanahan, HaniaSzajewska, Alan Thomson and Anton Le Mair. (2017). World Gastroenterology OrganizationGlobal Guideline: Probiotics and prebiotics.
[17]	Tuomola E, Ross C, Martin P, Erika I and Seppo S (2001): Quality assurance criteria for probiotic bacteria. Am J Clin Nutr73: 393-8.
[18]	Simon, O. (2015). Micro-organisms as feed additives—Probiotics. Adv. Pork Prod., 16: 161-167.
[19]	Lee, Y.K (2009). Selection and maintenance of probiotic microorganisms. In Handbook of Probiotics and Prebiotics, Lee, Y.K., Salminen, S., Eds., Wiley-VCH:Weinheim, Germany, 177-187.
[20]	Hill, C. Guarner, F. Reid, G. Gibson, G.R. Merenstein, D.J. Pot, B. Morelli, L. Canani, R.B. Flint, H.J. and Salminen, S. (2014). Expert consensus document: The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat. Rev. Gastroenterol. Hepatol., 11: 506-514.
[21]	Paulina M., Katarzyna and Sli˙z. (2017). Effects of Probiotics, Prebiotics, and Synbiotics on Human Health.
[22]	Amiya K., Rautray R., Patra C., Sardar K. and Sahoo G. (2011). Potential of Probiotics in Livestock Production. Eamr., 1: 20-8.
[23]	Ayichew T., Belete A., Alebachew T., Tsehaye H., Berhanu H. and Minwuyelet. (2017). Bacterial Probiotics their Importances and Limitations. J. Nutr. and Heal. Sci., 39: 1-30.
[24]	Ohland CL., MacnaughtonWK. (2010). Probiotic bacteria and intestinal epithelial barrier function. J. Phys. Gastr. Liv. 298: 807-819.
[25]	Carasi P., D´ıaz M., S. M. Racedo. (2014). Safety characterization and antimicrobial properties of kefir-isolated Lactobacilluskefiri. Bio.Med. Res. Inter., 3:7.
[26]	Parisa Shokryazdan, Chin ChinSieo, Ramasamy Kalavathy, Juan Boo Liang, Noorjahan Banu Alitheen, Mohammad FaselehJahromi, and Yin Wan Ho1. (2014). Probiotic Potential of Lactobacillus Strains with Antimicrobial. Activity against Some Human Pathogenic Strains.Bio. Med. Res. Intern., 1:1-16
[27]	Zhang ZF, Kim IH. Effects of multistrain probiotics on growth performance, apparent ileal nutrient digestibility, blood characteristics, cecal microbial shedding, and excreta odor contents in broilers. Poult Sci. 2014 Feb; 93(2): 364-70.
[28]	Martins F, Dalmasso G, Arantes M, Doye A, Lemichez E, et al. (2010). Interaction of Saccharomyces boulardii with Salmonella enteric serovar Typhimurium protects mice and modifies T84 cell response to the infection. Plos One 5: 1932-2203.
[29]	Kamila G., Sonia A. and Teresa A. (2018). Helicobacter pylori treatment: antibiotics or probiotics. Appl. Microbiol. Biotech., 102: 1-7.
[30]	Johnson-Henry KC, Hagen KE, Gordonpour M, Tompkins TA, Sherman PM. Surface-layer protein extracts from Lactobacillus helveticus inhibit enterohaemorrhagic Escherichia coli O157:H7 adhesion to epithelial cells. Cell Microbiol. 2007 Feb; 9(2): 356-67.
[31]	Hanisch FG., Bonar D., Schloerer N., Schroten H. (2014). Human trefoil factor 2 is a lectin that binds α-GlcNAc-capped mucin glycans with antibiotic activity against Helicobacter pylori. J. Biol. Chem.289: 27363-27375.
[32]	Mercenier A, Pavan S and Pot B. (2002). Probiotics as biotherapeutic agents. Present knowledge and future prospects. Curr. Pharm. Des. 8: 99-110.
[33]	Vijaya K Gogineni1, Lee E Morrow and Mark AMalesker. (2013). Probiotics: Mechanisms of Action and Clinical Applications. J. Prob Health, 1:1-11.
[34]	NikbakhtNasrabadi, E.; Jamaluddin, R.; Abdul Mutalib, M.S.; Khaza’ai, H.; Khalesi, S.; Mohd and Redzwan, S. (2013). Reduction of aflatoxin level in aflatoxin-induced rats by the activity of probiotic Lactobacillus casei strain Shirota. J. Appl. Microbiol., 114: 1507-1515
[35]	Shinde PB. (2012). Proobiotic: An Overview for Selction And Evaluation. Intern. J. Pharm. Pharmaceu. Scie. 4: 14-50
[36]	Moslehi-Jenabian S, Pedersen LL, Jespersen L. Beneficial effects of probiotic and food borne yeasts on human health. Nutrients. 2010 Apr; 2(4):449-73.
[37]	Didari T, Mozaffari S, Nikfar S, Abdollahi M. Effectiveness of probiotics in irritable bowel syndrome: Updated systematic review with meta-analysis. World J Gastroenterol. 2015; 21(10): 3072-3084.
[38]	Limketkai BN, Akobeng AK, Gordon M, Adepoju AA. Probiotics for induction of remission in Crohn's disease. Cochrane Database Syst Rev. 2020 Jul 17; 7(7): CD006634.
[39]	Boaventura C, Rafael A, Ana U, Jacques N, Luis G (2012). The Benefits of Probiotics in Human and Animal Nutrition. NAB Clinical Gastroenterology. In Tech, Europe 75-100.
[40]	Vahedi H., Ansari R., Nasseri M., Jafari E. (2010). Irritable Bowel Syndrome. Mid E J Dgtv Dis2: 28-49.
[41]	Bermudez-Brito M, Plaza-Díaz J, Muñoz-Quezada S, Gómez-Llorente C, Gil A. Probiotic mechanisms of action. Ann Nutr Metab. 2012; 61(2): 160-74.
[42]	Rukshana S, Jayasree V, Nirmala C. Role of probiotics in lower reproductive tract infection in women of age group 18 to 45 years. Int J Reprod Contracept Obstet Gynecol. 2017; 6(2): 671-81.
[43]	Bordoni A., Amaretti A. and Leonardi A. (2013). Cholesterol lowering probiotics: In vitro selection and in vivo testing of ifidobacterial. Appl Microbiol Biotechnol., 9: 8273-81.
[44]	Catherine TD., Mitchell LJ. and Divya S. (2014). Cholesterol assimilation by Lactobacillus probiotic bacteria: An in vitro investigation. Bio. Med. ReS. Int., 6: 1-9.
[45]	Vaishnavi K, Krishma M and Rajeswari P. (2016). A study on cholesterol degradation by Lactobacillus. Ind. J. Appl. Res.
[46]	Patel AK, Singhania RR and Pandey A. (2010). Probiotic bile salt hydrolase: current developments and perspectives. Appl. Biochem. Biotechnol., 162: 166-80.
[47]	Olas B. Probiotics, Prebiotics and Synbiotics-A Promising Strategy in Prevention and Treatment of Cardiovascular Diseases?. Int J Mol Sci. 2020; 21(24): 9737. Published 2020 Dec 20.
[48]	Oniszczuk A, Oniszczuk T, Gancarz M, Szymańska J. Role of Gut Microbiota, Probiotics and Prebiotics in the Cardiovascular Diseases. Molecules. 2021; 26(4): 1172. Published 2021 Feb 22.
[49]	Kabeerdoss J., Devi RS and Mary RR. (2011). Effect of yoghurt containing Bifidobacterium lactis Bb12 on fecal excretion of secretory immunoglobulin A and human beta-defensin 2 in healthy adult volunteers. Nutr. J. 10: 138.
[50]	Pietrzak B, Tomela K, Olejnik-Schmidt A, Mackiewicz A, Schmidt M. Secretory IgA in Intestinal Mucosal Secretions as an Adaptive Barrier against Microbial Cells. Int J Mol Sci. 2020 Dec 4; 21(23): 9254.
[51]	Corcionivoschi N, Drinceanu D, Pop IM, Stack D , Ştef L , Julean C, BourkeB. The Effect of Probiotics on Animal Health. Animal Science and Biotechnologies, 2010, 43 (1): 35-41.
[52]	Hatice Y. (2010). Isolation, Characterization, Determination of Probiotic Properties of Lactic Acid Bacteria from Human Milk, A Thesis Submitted to the Graduate School of Engineering and Sciences of Izmir Institute of Technology in Partial Fulfillment of the Requirements for the Degree of Master of Science in Food Engineering. 1-69
[53]	Moro García MA., Alonso Arias R. and Baltadjieva M. (2013). Oral supplementation with Lactobacillus delbrueckii subsp. bulgaricus 8481 enhances systemic immunity in elderly subjects. 35: 1311-1326.
[54]	Sullivan D. J. O. (2012). Exploring the potential to utilize lantibioticproducingbidobacteria to create dairy ingredients withincreasedbroadspectrum antimicrobial functionalities yieldsencouraging results. J. F. Tech., 66: 45-50.
[55]	ShyamalaR, Gowri P and Meenambigai P. (2016). Probiotics and its effects on human health. Int. J. Curr. Microbiol. App. Sci. 5: 384-392.
[56]	Ewe J. A., Wan Nadiah W. A., and Liong M. T. (2010). Viability and growth characteristics of Lactobacillus in soymilk supplemented with B-vitamins. Inter. J. F. Sci.and Nutr., 61: 87-107
[57]	Ho H-H, Chen C-W, Huang Y-F, et al. The Novel Use of Postbiotics of TYCA06/AP-32/CP-9 in the Amelioration of Atopic Dermatitis and Improvement of Skin Care - A Clinical Study. International Journal of Clinical and Diagnostic Research. 2021, 9(1), 18-28.
[58]	Stavropoulou E and Bezirtzoglou E. (2020). Probiotics in Medicine: A Long Debate. Front. Immunol. 11: 2192.
[59]	Din AU, Mazhar M, Waseem M, Ahmad W, Bibi A, Hassan A, Ali N, Gang W, Qian G, Ullah R, Shah T, Ullah M, Khan I, Nisar MF, Wu J. SARS-CoV-2 microbiome dysbiosis linked disorders and possible probiotics role. Biomed Pharmacother. 2021 Jan; 133: 110947.
[60]	Gohil K, Samson R, Dastager S, Dharne M. Probiotics in the prophylaxis of COVID-19: something is better than nothing. 3 Biotech. 2021 Jan; 11(1): 1.
[61]	Dhar D, Mohanty A. Gut microbiota and Covid-19- possible link and implications. Virus Res. 2020 Aug; 285: 198018.
[62]	Shahbazi R, Yasavoli-Sharahi H, Alsadi N, Ismail N, Matar C. Probiotics in Treatment of Viral Respiratory Infections and Neuroinflammatory Disorders. Molecules. 2020 Oct 22; 25(21): 4891.
[63]	Mrityunjaya M, Pavithra V, Neelam R, Janhavi P, Halami PM, Ravindra PV. Immune-Boosting, Antioxidant and Anti-inflammatory Food Supplements Targeting Pathogenesis of COVID-19. Front Immunol. 2020 Oct 7; 11: 570122.
[64]	Reuben RC, Makut MD, Adogo LY. Probiotics potentials in mitigating coronavirus disease (COVID-19) pandemic. Pan Afr Med J. 2021 Feb 18; 38: 186.
[65]	Akour A. Probiotics and COVID-19: is there any link? Lett Appl Microbiol. 2020 Sep; 71(3): 229-234.
[66]	Bottari B, Castellone V, Neviani E. Probiotics and Covid-19. Int J Food Sci Nutr. 2021 May; 72(3): 293-299.
[67]	Gautier T, David-Le Gall S, Sweidan A, Tamanai-Shacoori Z, Jolivet-Gougeon A, Loréal O, Bousarghin L. Next-Generation Probiotics and Their Metabolites in COVID-19. Microorganisms. 2021 Apr 27; 9(5): 941.
[68]	Walton GE, Gibson GR, Hunter KA. Mechanisms linking the human gut microbiome to prophylactic and treatment strategies for COVID-19. Br J Nutr. 2021 Jul 28; 126(2): 219-227.
[69]	Kurian SJ, Unnikrishnan MK, Miraj SS, Bagchi D, Banerjee M, Reddy BS, Rodrigues GS, Manu MK, Saravu K, Mukhopadhyay C, Rao M. Probiotics in Prevention and Treatment of COVID-19: Current Perspective and Future Prospects. Arch Med Res. 2021 Mar 19: S0188-4409(21)00047-3.
[70]	Sivamaruthi BS, Prasanth MI, Kesika P, Chaiyasut C. Probiotics in human mental health and diseases-A mini review. Trop J Pharm Res, April 2019; 18(4): 890.
[71]	Sharma V, Kaur S. The Effect of Probiotic Intervention in Ameliorating the Altered Central Nervous System Functions in Neurological Disorders: A Review. Open Microbiology Journal. 2020; 14: 18-29.
[72]	Shin DY, Park J, Yi DY. Comprehensive Analysis of the Effect of Probiotic Intake by the Mother on Human Breast Milk and Infant Fecal Microbiota. J Korean Med Sci. 2021 Mar; 36(8): e58.
[73]	Baldwin H, Tan J. Effects of Diet on Acne and Its Response to Treatment. Am J Clin Dermatol. 2021 Jan; 22(1): 55-65.
[74]	Bhattacharya S. The Role of Probiotics in the Amelioration of Cadmium Toxicity. Biol Trace Elem Res. 2020 Oct; 197(2): 440-444.
[75]	Darbandi A, Asadi A, Ghanavati R, Afifirad R, Darb Emamie A, Kakanj M, Talebi M. The effect of probiotics on respiratory tract infection with special emphasis on COVID-19: Systemic review 2010-20. Int J Infect Dis. 2021 Apr; 105: 91-104.
[76]	Wang Z, He Y, Zheng Y. Probiotics for the Treatment of Bacterial Vaginosis: A Meta-Analysis. Int J Environ Res Public Health. 2019 Oct 12; 16(20): 3859.
[77]	Mantaring J, Benyacoub J, Destura R, Pecquet S, Vidal K, Volger S, Guinto V. Effect of maternal supplement beverage with and without probiotics during pregnancy and lactation on maternal and infant health: a randomized controlled trial in the Philippines. BMC Pregnancy Childbirth. 2018 May 31; 18(1): 193.
[78]	Sivamaruthi BS, Suganthy N, Kesika P, Chaiyasut C. The Role of Microbiome, Dietary Supplements, and Probiotics in Autism Spectrum Disorder. Int J Environ Res Public Health. 2020 Apr 12; 17(8): 2647.
[79]	Salehi B, Dimitrijević M, Aleksić A, Neffe-Skocińska K, Zielińska D, Kołożyn-Krajewska D, Sharifi-Rad J, Stojanović-Radić Z, Prabu SM, Rodrigues CF, Martins N. Human microbiome and homeostasis: insights into the key role of prebiotics, probiotics, and symbiotics. Crit Rev Food Sci Nutr. 2021; 61(9): 1415-1428.
[80]	Ederveen THA, Smits JPH, Boekhorst J, Schalkwijk J, van den Bogaard EH, Zeeuwen PLJM. Skin microbiota in health and disease: From sequencing to biology. J Dermatol. 2020 Oct; 47(10): 1110-1118.
[81]	Giles EM, Couper J. Microbiome in health and disease. J Paediatr Child Health. 2020 Nov; 56(11): 1735-1738.
[82]	Sharifi-Rad J, Rodrigues CF, Stojanović-Radić Z, Dimitrijević M, Aleksić A, Neffe-Skocińska K, Zielińska D, Kołożyn-Krajewska D, Salehi B, Milton Prabu S, Schutz F, Docea AO, Martins N, Calina D. Probiotics: Versatile Bioactive Components in Promoting Human Health. Medicina (Kaunas). 2020 Aug 27; 56(9): 433.
[83]	Rudzki L, Stone TW, Maes M, Misiak B, Samochowiec J, Szulc A. Gut microbiota-derived vitamins - underrated powers of a multipotent ally in psychiatric health and disease. Prog Neuropsychopharmacol Biol Psychiatry. 2021 Apr 20; 107: 110240.
[84]	Wang H, He S, Xin J, Zhang T, Sun N, Li L, Ni X, Zeng D, Ma H, Bai Y. Psychoactive Effects of Lactobacillus johnsonii Against Restraint Stress-Induced Memory Dysfunction in Mice Through Modulating Intestinal Inflammation and permeability-a Study Based on the Gut-Brain Axis Hypothesis. Front Pharmacol. 2021 May 26; 12:662148.
[85]	Sharma P, Agrawal A. Does modern research validate the ancient wisdom of gut flora and brain connection? A literature review of gut dysbiosis in neurological and neurosurgical disorders over the last decade. Neurosurg Rev. 2021 Apr 26.
[86]	Lubomski M, Tan AH, Lim SY, Holmes AJ, Davis RL, Sue CM. Parkinson's disease and the gastrointestinal microbiome. J Neurol. 2020 Sep; 267(9): 2507-2523.
[87]	Doifode T, Giridharan VV, Generoso JS, Bhatti G, Collodel A, Schulz PE, Forlenza OV, Barichello T. The impact of the microbiota-gut-brain axis on Alzheimer's disease pathophysiology. Pharmacol Res. 2021 Feb; 164: 105314.
[88]	Wang X, Liang Z, Wang S, Ma D, Zhu M, Feng J. Role of Gut Microbiota in Multiple Sclerosis and Potential Therapeutic Implications. Curr Neuropharmacol. 2021 Jun 29.
[89]	Cuna A, Morowitz MJ, Ahmed I, Umar S, Sampath V. Dynamics of the preterm gut microbiome in health and disease. Am J Physiol Gastrointest Liver Physiol. 2021 Apr 1; 320(4): G411-G419.
[90]	Ghosh TS, Arnoux J, O'Toole PW. Metagenomic analysis reveals distinct patterns of gut lactobacillus prevalence, abundance, and geographical variation in health and disease. Gut Microbes. 2020 Nov 9; 12(1): 1-19.
[91]	Hamilton-Williams EE, Lorca GL, Norris JM, Dunne JL. A Triple Threat? The Role of Diet, Nutrition, and the Microbiota in T1D Pathogenesis. Front Nutr. 2021 Apr 1; 8:600756.
[92]	AlHilli MM, Bae-Jump V. Diet and gut microbiome interactions in gynecologic cancer. Gynecol Oncol. 2020 Nov; 159(2): 299-308.
[93]	Zhang J, Xia Y, Sun J. Breast and gut microbiome in health and cancer. Genes Dis. 2020 Aug 20; 8(5): 581-589.
[94]	Karl JP. Gut Microbiota-targeted Interventions for Reducing the Incidence, Duration, and Severity of Respiratory Tract Infections in Healthy Non-elderly Adults. Mil Med. 2021 Feb 26; 186(3-4): e310-e318.
[95]	Kiousi DE, Rathosi M, Tsifintaris M, Chondrou P, Galanis A. Pro-biomics: Omics Technologies to Unravel the Role of Probiotics in Health and Disease. Adv Nutr. 2021 Feb 24: nmab014.
[96]	Su GL, Ko CW, Bercik P, Falck-Ytter Y, Sultan S, Weizman AV, Morgan RL. AGA Clinical Practice Guidelines on the Role of Probiotics in the Management of Gastrointestinal Disorders. Gastroenterology. 2020 Aug; 159(2): 697-705.
[97]	Benmoussa A, Provost P. Milk MicroRNAs in Health and Disease. Compr Rev Food Sci Food Saf. 2019 May; 18(3): 703-722.
[98]	Piqué N, Berlanga M, Miñana-Galbis D. Health Benefits of Heat-Killed (Tyndallized) Probiotics: An Overview. Int J Mol Sci. 2019 May 23; 20(10): 2534.
[99]	Suez J, Zmora N, Segal E, Elinav E. The pros, cons, and many unknowns of probiotics. Nat Med. 2019 May; 25(5): 716-729.
[100]	Jankovic I, Sybesma W, Phothirath P, Ananta E, Mercenier A. Application of probiotics in food products--challenges and new approaches. Curr Opin Biotechnol. 2010 Apr; 21(2): 175-81.
[101]	BinnsN (2013). ILSI Europe Concise Monograph Series Probiotics. Prebio Gut Microbi. 2: 1-31.
[102]	Tang H, Bohannon L, Lew M, Jensen D, Jung SH, Zhao A, Sung AD, Wischmeyer PE. Randomised, double-blind, placebo-controlled trial of Probiotics To Eliminate COVID-19 Transmission in Exposed Household Contacts (PROTECT-EHC): a clinical trial protocol. BMJ Open. 2021 May 5; 11(5): e047069.
[103]	Haran JP, Pinero JC, Zheng Y, Palma NA, Wingertzahn M. Virtualized clinical studies to assess the natural history and impact of gut microbiome modulation in non-hospitalized patients with mild to moderate COVID-19 a randomized, open-label, prospective study with a parallel group study evaluating the physiologic effects of KB109 on gut microbiota structure and function: a structured summary of a study protocol for a randomized controlled study. Trials. 2021 Apr 2; 22(1): 245.
[104]	Coffey MJ, Garg M, Homaira N, Jaffe A, Ooi CY. Probiotics for people with cystic fibrosis. Cochrane Database Syst Rev. 2020; 1(1): CD012949. Published 2020 Jan 22.
[105]	Hardouin P, Chiron R, Marchandin H, Armengaud J, Grenga L. Metaproteomics to Decipher CF Host-Microbiota Interactions: Overview, Challenges and Future Perspectives. Genes (Basel). 2021; 12(6): 892. Published 2021 Jun 9.
[106]	Tahir H. (2013): Probiotics and controversies. J. Microbio. Antimicrobio. 5: 1-5.