Probiotic Lactobacillus and the potential risk of spreading antibiotic resistance: a systematic review

Ali Shahali , Rasool Soltani, Vajihe Akbari

Abstract


Background and purpose: Lactobacillus, the most popular probiotic, has recently gained more attention because it is a potential reservoir of antibiotic resistance. This review summarized and discussed the phenotypic-genotypic characteristics of antibiotic resistance.

Experimental approach: Google Scholar, PubMed, Web of Science, and Scopus were searched                                     up to February 2022. The inclusion criteria were all studies testing antibiotic resistance of probiotic Lactobacillus strains present in human food supplementation and all human/animal model studies                                    in which transferring antibiotic-resistant genes from Lactobacillus strains to another bacterium were investigated.


Findings/Results: Phenotypic and genotypic characterization of Lactobacillus probiotics showed that the most antibiotic resistance was against protein synthesis inhibitors (fourteen studies, 87.5%) and cell wall synthesis inhibitors (ten studies, 62.5%). Nine of these studies reported the transfer of antibiotic resistance from Lactobacillus probiotic as donor species to ‎pathogenic bacteria and mostly used in vitro methods for resistance gene transfer.

Conclusion and implications: The transferability of resistance genes such as tet and erm in Lactobacillus increases the risk of spreading antibiotic resistance. Further studies need to be conducted to evaluate the potential spread of antibiotic resistance traits via probiotics, especially in elderly people and newborns.

Highlights

Vajihe Akbari: PubMed, Google Scholar

Rasool Soltani; PubMed


Keywords


Antibiotic resistance; Lactobacillus probiotic, Probiotic safety; Systematic review.

Full Text:

PDF

References


Vandenplas Y, Huys G, Daube G. Probiotics: an update. J Pediatr (Rio J). 2015;91(1):6-21. DOI: 10.1016/j.jped.2014.08.005.

Daniali M, Nikfar S, Abdollahi M. Antibiotic resistance propagation through probiotics. Expert Opin Drug Metab Toxicol. 2020;16(12):1207-1215.DOI: 10.1080/17425255.2020.1825682.

Cunningham M, Azcarate-Peril MA, Barnard A, Benoit V, Grimaldi R, Guyonnet D, et al. Shaping the future of probiotics and prebiotics. Trends Microbiol. 2021;29(8):667-685.DOI: 10.1016/j.tim.2021.01.003.

Abedi D, Feizizadeh S, Akbari V, Jafarin-Dehkordi A. In vitro anti-bacterial and anti-adherence effects of Lactobacillus delbrueckii subsp. bulgaricus on Escherichia coli. Res Pharm Sci. 2013;8(4):261-268. PMID: 24082895.

Reininghaus EZ, Wetzlmair LC, Fellendorf FT, Platzer M, Queissner R, Birner A, et al. Probiotic treatment in individuals with euthymic bipolar disorder: a pilot-study on clinical changes and compliance. Neuropsychobiology. 2020;79(1):71-79.DOI: 10.1159/000493867.

Akbari V, Hendijani F. Effects of probiotic supplementation in patients with type 2 diabetes: systematic review and meta-analysis. Nutr Rev. 2016;74(12):774-784. DOI: 10.1093/nutrit/nuw039.

Hendijani F, Akbari V. Probiotic supplementation for management of cardiovascular risk factors in adults with type II diabetes: a systematic review and meta-analysis. Clin Nutr. 2018;37(2):532-541. DOI: 10.1016/j.clnu.2017.02.015.

Avand A, Akbari V, Shafizadegan S. In vitro cytotoxic activity of a Lactococcus lactis antimicrobial peptide against breast cancer cells. Iran J Biotechnol. 2018;16(3):e1867,213-220. DOI: 10.15171/ijb.1867.

Feizizadeh S, Salehi-Abargouei A, Akbari V. Efficacy and safety of Saccharomyces boulardii for acute diarrhea. Pediatrics. 2014;134(1):e176-e191. DOI: 10.1542/peds.2013-3950.

Wallace TC. Twenty years of the dietary supplement health and education act-how should dietary supplements be regulated? J Nutr. 2015;145(8):1683-1686. DOI: 10.3945/jn.115.211102.

Shokryazdan P, Sieo CC, Kalavathy R, Liang JB, Alitheen NB, Jahromi MF, et al. Probiotic potential of Lactobacillus strains with antimicrobial activity against some human pathogenic strains. Biomed Res Int. 2014;2014:927268,1-16. DOI: 10.1155/2014/927268.

Zheng M, Zhang R, Tian X, Zhou X, Pan X, Wong A. Assessing the risk of probiotic dietary supplements in the context of antibiotic resistance. Front Microbiol. 2017;8:908,1-8. DOI: 10.3389/fmicb.2017.00908.

Broaders E, Gahan CGM, Marchesi JR. Mobile genetic elements of the human gastrointestinal tract: potential for spread of antibiotic resistance genes. Gut Microbes. 2013;4(4):271-280. DOI: 10.4161/gmic.24627.

Jose NM, Bunt CR, Hussain MA. Implications of antibiotic resistance in probiotics. Food Rev Int. 2015;31(1):52-62. DOI: 10.1080/87559129.2014.961075.

Imperial ICVJ, Ibana JA. Addressing the antibiotic resistance problem with probiotics: reducing the risk of its double-edged sword effect. Front Microbiol. 2016;7:1983,1-10. DOI: 10.3389/fmicb.2016.01983.

Abriouel H, del Carmen Casado Muñoz M, Lerma LL, Montoro BP, Bockelmann W, Pichner R, et al. New insights in antibiotic resistance of Lactobacillus species from fermented foods. Food Res Int.2015;78:465-481. DOI: 10.1016/j.foodres.2015.09.016.

Snydman DR. The safety of probiotics. Clin Infect Dis. 2008;46(Suppl 2):S104-S111. DOI: 10.1086/523331.

Aarts H, Margolles A. Antibiotic resistance genes in food and gut (non-pathogenic) bacteria. Bad genes in good bugs. Front Microbiol. 2015;5:754,1-2. DOI: 10.3389/fmicb.2014.00754.

Campedelli I, Mathur H, Salvetti E, Clarke S, Rea MC, Torriani S, et al. Genus-wide assessment of antibiotic resistance in Lactobacillus spp. Appl Environ Microbiol. 2019;85(1):e01738-18,1-21. DOI: 10.1128/AEM.01738-18.

Katla T, Møretrø T, Aasen IM, Holck A, Axelsson L, Naterstad K. Inhibition of Listeria monocytogenes in cold smoked salmon by addition of sakacin P and/or live Lactobacillus sakei cultures. Food Microbiol. 2001;18(4):431-439. DOI: 10.1006/fmic.2001.0420.

Mascaretti OA. Bacteria versus antibacterial agents: an integrated approach. USA: American Society for Microbiology (ASM); 2003. pp. 393.

Huys G, D'haene K, Danielsen M, Mättö J, Egervärn M, Vandamme P. Phenotypic and molecular assessment of antimicrobial resistance in Lactobacillus paracasei strains of food origin. J Food Prot. 2008;71(2):339-344. DOI: 10.4315/0362-028x-71.2.339.

Comunian R, Daga E, Dupré I, Paba A, Devirgiliis C, Piccioni V, et al. Susceptibility to tetracycline and erythromycin of Lactobacillus paracasei strains isolated from traditional Italian fermented foods. Int J Food Microbiol. 2010;138(1-2):151-156. DOI: 10.1016/j.ijfoodmicro.2009.11.018.

Devirgiliis C, Zinno P, Perozzi G. Update on antibiotic resistance in foodborne Lactobacillus and Lactococcus species. Front Microbiol. 2013;4:301, 1-13. DOI: 10.3389/fmicb.2013.00301.

Thumu SCR, Halami PM. Presence of erythromycin and tetracycline resistance genes in lactic acid bacteria from fermented foods of Indian origin. Antonie Van Leeuwenhoek. 2012;102:541-551. DOI: 10.1007/s10482-012-9749-4.

Thumu SCR, Halami PM. Conjugal transfer of erm (B) and multiple tet genes from Lactobacillus spp. to bacterial pathogens in animal gut, in vitro and during food fermentation. Food Res Int. 2019;116: 1066-1075. DOI: 10.1016/j.foodres.2018.09.046.

Ammor MS, Flórez AB, van Hoek AHAM, de los Reyes-Gavilán CG, Aarts HJM, Abelardo M, et al. Molecular characterization of intrinsic and acquired antibiotic resistance in lactic acid bacteria and bifidobacteria. J Mol Microbiol Biotechnol. 2008;14(1-3):6-15. DOI: 10.1159/000106077.

Ojha AK, Shah NP, Mishra V. Conjugal transfer of antibiotic resistances in Lactobacillus spp. Curr Microbiol. 2021;78:2839-2849. DOI: 10.1007/s00284-021-02554-1.

Toomey N, Monaghan Á, Fanning S, Bolton D. Transfer of antibiotic resistance marker genes between lactic acid bacteria in model rumen and plant environments. Appl Environ Microbiol. 2009;75(10):3146-3152. DOI: 10.1128/AEM.02471-08.

Esaiassen E, Hjerde E, Cavanagh JP, Pedersen T, Andresen JH, Rettedal SI, et al. Effects of probiotic supplementation on the gut microbiota and antibiotic resistome development in preterm infants. Front Pediatr. 2018;6:347,1-16. DOI: 10.3389/fped.2018.00347.

Butler CC, Lau M, Gillespie D, Owen-Jones E, Lown M, Wootton M, et al. Effect of probiotic use on antibiotic administration among care home residents: a randomized clinical trial. JAMA. 2020;324(1):47-56. DOI: 10.1001/jama.2020.8556.

Rowland IR, Capurso L, Collins K, Cummings J, Delzenne N, Goulet O, et al. Current level of consensus on probiotic science-Report of an expert meeting-London, 23 November 2009. Gut Microbes. 2010;1(6):436-439.DOI: 10.4161/gmic.1.6.13610.

Eggers S, Barker AK, Valentine S, Hess T, Duster M, Safdar N. Effect of Lactobacillus rhamnosus HN001 on carriage of Staphylococcus aureus: results of the impact of probiotics for reducing infections in veterans (IMPROVE) study. BMC Infect Dis. 2018;18:129,1-8. DOI: 10.1186/s12879-018-3028-6.

Liu G, Pang B, Li N, Jin H, Li J, Wu W, et al. Therapeutic effect of Lactobacillus rhamnosus SHA113 on intestinal infection by multi-drug-resistant Staphylococcus aureus and its underlying mechanisms. Food Funct. 2020;11(7):1-34. DOI: 10.1039/d0fo00969e.

Neut C, Mahieux S, Dubreuil LJ. Antibiotic susceptibility of probiotic strains: is it reasonable to combine probiotics with antibiotics? Med Mal Infect. 2017;47(7):477-483. DOI: 10.1016/j.medmal.2017.07.001.

Askelson TE, Flores CA, Dunn-Horrocks SL, Dersjant-Li Y, Gibbs K, Awati A, et al. Effects of direct-fed microorganisms and enzyme blend co-administration on intestinal bacteria in broilers fed diets with or without antibiotics. Poult Sci. 2018;97(1):54-63. DOI: 10.3382/ps/pex270.

Rao KP, Chennappa G, Suraj U, Nagaraja H, Raj APC, Sreenivasa MY. Probiotic potential of Lactobacillus strains isolated from sorghum-based traditional fermented food. Probiotics Antimicrob Proteins. 2015;7:146-156. DOI: 10.1007/s12602-015-9186-6.

James L, Beena AK, Anupa A, Sreeshma N. Antibiogram of Lactobacilli isolated from four different niches. J Microbiol Microb Technol. 2016;1(1):4,1-4.DOI: 10.13188/2474-4530.1000002.

Zhou JS, Pillidge CJ, Gopal PK, Gill HS. Antibiotic susceptibility profiles of new probiotic Lactobacillus and Bifidobacterium strains. Int J Food Microbiol. 2005;98(2):211-217. DOI: 10.1016/j.ijfoodmicro.2004.05.011.

del Carmen Casado Muñoz M, Benomar N, Lerma LL, Gálvez A, Abriouel H. Antibiotic resistance of Lactobacillus pentosus and Leuconostoc pseudomesenteroides isolated from naturally-fermented Aloreña table olives throughout fermentation process. Int J Food Microbiol. 2014;172:110-118. DOI: 10.1016/j.ijfoodmicro.2013.11.025.

Zhou N, Zhang JX, Fan MT, Wang J, Guo G, Wei XY. Antibiotic resistance of lactic acid bacteria isolated from Chinese yogurts. J Dairy Sci. 2012;95(9):4775-4783. DOI: 10.3168/jds.2011-5271.

Prete R, Long SL, Joyce SA, Corsetti A. Genotypic and phenotypic characterization of food-associated Lactobacillus plantarum isolates for potential probiotic activities. FEMS Microbiol Lett. 2020;367(10):fnaa076,1-19. DOI: 10.1093/femsle/fnaa076.

Hassan MUI, Nayab H, Shafique F, Williamson MP, Almansouri TS, Asim N, et al. Probiotic properties of Lactobacillus helveticus and Lactobacillus plantarum isolated from traditional Pakistani yoghurt. BioMed Res Int. 2020;2020:8889198,1-17. DOI: 10.1155/2020/8889198.

Blandino G, Milazzo I, Fazio D. Antibiotic susceptibility of bacterial isolates from probiotic products available in Italy. Microb Ecol Health Dis. 2008;20(4):199-203. DOI: 10.1080/08910600802408111.

Sornsenee P, Singkhamanan K, Sangkhathat S, Saengsuwan P, Romyasamit C. Probiotic properties of Lactobacillus species isolated from fermented palm sap in Thailand. Probiotics Antimicrob Proteins. 2021;13:957-969. DOI: 10.1007/s12602-021-09754-y.

Wang K, Zhang H, Feng J, Ma L, de la Fuente-Núnez C, Wang S, et al. Antibiotic resistance of lactic acid bacteria isolated from dairy products in Tianjin, China. J Agric Food Res. 2019;1:100006,1-5. DOI: 10.1016/j.jafr.2019.100006.

Lee BS, Ban OH, Bang WY, Chae SA, Oh S, Park C, et al. Safety assessment of Lactobacillus reuteri IDCC 3701 based on phenotypic and genomic analysis. Ann Microbiol. 2021;71:10,1-6. DOI: 10.1186/s13213-021-01622-y.

Hummel AS, Hertel C, Holzapfel WH, Franz CMAP. Antibiotic resistances of starter and probiotic strains of lactic acid bacteria. Appl Environ Microbiol. 2007;73(3):730-739. DOI: 10.1128/AEM.02105-06.

Shafiei Seifabadi F, Baserisalehi M. Plasmid-mediated antibiotic-resistant pattern of Lactobacillus spp. isolated from dairy products. Avicenna J Clin Microbiol Infect. 2021;8(1):1-4. DOI: 10.34172/ajcmi.2021.01.

Karapetkov N, Georgieva R, Rumyan N, Karaivanova E. Antibiotic susceptibility of different lactic acid bacteria strains. Benef Microbes. 2011;2(4):335-339. DOI: 10.3920/BM2011.0016.

Guo H, Pan L, Li L, Lu J, Kwok L, Menghe B, et al. Characterization of antibiotic resistance genes from Lactobacillus isolated from traditional dairy products. J Food Sci. 2017;82(3):724-730. DOI: 10.1111/1750-3841.13645.

Zonenschain D, Rebecchi A, Morelli L. Erythromycin‐and tetracycline‐resistant Lactobacilli in Italian fermented dry sausages. J Appl Microbiol. 2009;107(5):1559-1568. DOI: 10.1111/j.1365-2672.2009.04338.x.

Nawaz M, Wang J, Zhou A, Ma C, Wu X, Moore JE, et al. Characterization and transfer of antibiotic resistance in lactic acid bacteria from fermented food products. Curr Microbiol. 2011;62:1081-1089. DOI: 10.1007/s00284-010-9856-2.

Kastner S, Perreten V, Bleuler H, Hugenschmidt G, Lacroix C, Meile L. Antibiotic susceptibility patterns and resistance genes of starter cultures and probiotic bacteria used in food. Syst Appl Microbiol. 2006;29(2):145-155. DOI: 10.1016/j.syapm.2005.07.009.

Klein G. Antibiotic resistance and molecular characterization of probiotic and clinical Lactobacillus strains in relation to safety aspects of probiotics. Foodborne Pathog Dis. 2011;8(2):267-281. DOI: 10.1089/fpd.2010.0672.

Gevers D, Huys G, Swings J. In vitro conjugal transfer of tetracycline resistance from Lactobacillus isolates to other Gram-positive bacteria. FEMS Microbiol Lett. 2003;225(1):125-130. DOI: 10.1016/S0378-1097(03)00505-6.

Rosander A, Connolly E, Roos S. Removal of antibiotic resistance gene-carrying plasmids from Lactobacillus reuteri ATCC 55730 and characterization of the resulting daughter strain, L. reuteri DSM 17938. Appl Environ Microbiol. 2008;74(19):6032-6040. DOI: 10.1128/AEM.00991-08.

Rodríguez-Sánchez S, Ramos IM, Seseña S, Poveda JM, Palop ML. Potential of Lactobacillus strains for health-promotion and flavouring of fermented dairy foods. Food Sci Technol. 2021;143:111102,1-13. DOI: 10.1016/j.lwt.2021.111102.

Feld L, Schjørring S, Hammer K, Licht TR, Danielsen M, Krogfelt K, et al. Selective pressure affects transfer and establishment of a Lactobacillus plantarum resistance plasmid in the gastrointestinal environment. J Antimicrob Chemother. 2008;61(4):845-852. DOI: 10.1093/jac/dkn033.

Devirgiliis C, Coppola D, Barile S, Colonna B, Perozzi G. Characterization of the Tn916 conjugative transposon in a food-borne strain of Lactobacillus paracasei. Appl Environ Microbiol. 2009;75(12):3866-3871. DOI: 10.1128/AEM.00589-09.

Ojha AK, Shah NP, Mishra V. Conjugal transfer of antibiotic resistances in Lactobacillus spp. Curr Microbiol.2021;78(8),2839-2849.

Microbiol.2021;78(8),2839-2849. DOI: 10.1007/s00284-021-02554-1.

Jalali M, Abedi D, Varshosaz J, Najjarzadeh M, Mirlohi M, Tavakoli N. Stability evaluation of freeze-dried Lactobacillus paracasei subsp. tolerance and Lactobacillus delbrueckii subsp. bulgaricus in oral capsules. Res Pharm Sci. 2012;7(1):31-36.PMID: 23181077.


Refbacks

  • There are currently no refbacks.


Creative Commons LicenseThis work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.