Skip to main content Accessibility help

Factors influencing horizontal gene transfer in the intestine

  • Ximin Zeng (a1) and Jun Lin (a1)


Antibiotic resistance (AR) is ancient. Use of antibiotics is a selective driving force that enriches AR genes and promotes the emergence of resistant pathogens. It also has been widely accepted that horizontal gene transfer (HGT) occurs everywhere and plays a critical role in the transmission of AR genes among bacteria. However, our understanding of HGT processes primarily build on extensive in vitro studies; to date, there is still a significant knowledge gap regarding in situ HGT events as well as the factors that influence HGT in different ecological niches. This review is focused on the HGT process in the intestinal tract, a ‘melting pot’ for gene exchange. Several factors that potentially influence in vivo HGT efficiency in the intestine are identified and summarized, which include SOS-inducing agents, stress hormones, microbiota and microbiota-derived factors. We highlight recent discoveries demonstrating that certain antibiotics, which are widely used in animal industry, can enhance HGT in the intestine by serving as DNA-damaging, SOS-inducing agents. Despite recent progress, research on in vivo HGT events is still in its infancy. A better understanding of the factors influencing HGT in the intestine is highly warranted for developing effective strategies to mitigate AR in animal production as well as in future agricultural ecosystems.


Corresponding author

*Corresponding author. E-mail:


Hide All
Allen, HK, Looft, T, Bayles, DO, Humphrey, S, Levine, UY, Alt, D and Stanton, TB (2011). Antibiotics in feed induce prophages in swine fecal microbiomes. MBio 2: e00260e00211.
Alvarez-Martinez, CE and Christie, PJ (2009). Biological diversity of prokaryotic type IV secretion systems. Microbiology and Molecular Biology Reviews 73: 775808.
Amita, M, Chowdhury, SR, Thungapathra, M, Ramamurthy, T, Nair, GB and Ghosh, A (2003). Class I integrons and SXT elements in El Tor strains isolated before and after 1992 Vibrio cholerae O139 outbreak, Calcutta, India. Emerging Infectious Diseases 9: 500502.
Andersson, DI and Hughes, D (2010). Antibiotic resistance and its cost: is it possible to reverse resistance? Nature Reviews: Microbiology 8: 260271.
Barrett, E, Ross, RP, O'Toole, PW, Fitzgerald, GF and Stanton, C (2012). Gamma-aminobutyric acid production by culturable bacteria from the human intestine. Journal of Applied Microbiology 113: 411417.
Beaber, JW, Hochhut, B and Waldor, MK (2004). SOS response promotes horizontal dissemination of antibiotic resistance genes. Nature 427: 7274.
Broaders, E, Gahan, CG and Marchesi, JR (2013). Mobile genetic elements of the human gastrointestinal tract: potential for spread of antibiotic resistance genes. Gut Microbes 4: 271280.
Burrus, V and Waldor, MK (2004). Shaping bacterial genomes with integrative and conjugative elements. Research in Microbiology 155: 376386.
Burrus, V, Pavlovic, G, Decaris, B and Guedon, G (2002). Conjugative transposons: the tip of the iceberg. Molecular Microbiology 46: 601610.
Bush, K and Bradford, PA (2016). Beta-lactams and beta-lactamase inhibitors: an overview. Cold Spring Harbor Perspectives in Medicine 6: a025247.
Capozzi, V and Spano, G (2009). Horizontal gene transfer in the gut: is it a risk? Food Research International 42: 15011502.
Charpentier, X, Polard, P and Claverys, JP (2012). Induction of competence for genetic transformation by antibiotics: convergent evolution of stress responses in distant bacterial species lacking SOS? Current Opinion in Microbiology 15: 570576.
Christie, PJ and Vogel, JP (2000). Bacterial type IV secretion: conjugation systems adapted to deliver effector molecules to host cells. Trends in Microbiology 8: 354360.
Christie, PJ, Atmakuri, K, Krishnamoorthy, V, Jakubowski, S and Cascales, E (2005). Biogenesis, architecture, and function of bacterial type IV secretion systems. Annual Review of Microbiology 59: 451485.
Clewell, DB (2007). Properties of Enterococcus faecalis plasmid pAD1, a member of a widely disseminated family of pheromone-responding, conjugative, virulence elements encoding cytolysin. Plasmid 58: 205227.
Comeau, AM, Tetart, F, Trojet, SN, Prere, MF and Krisch, HM (2007). Phage-antibiotic synergy (PAS): beta-lactam and quinolone antibiotics stimulate virulent phage growth. PLoS ONE 2: e799.
Centers for Disease Control and Prevention (2013). Antibiotic resistance threats in the United States, 2013.
Crofts, TS, Gasparrini, AJ and Dantas, G (2017). Next-generation approaches to understand and combat the antibiotic resistome. Nature Reviews: Microbiology 15: 422434.
Cryan, JF and Dinan, TG (2012). Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nature Reviews: Neuroscience 13: 701712.
Curtiss, R 3rd (1969). Bacterial conjugation. Annual Review of Microbiology 23: 69136.
Davies, J (1996). Origins and evolution of antibiotic resistance. Microbiologia 12: 916.
Davies, J and Davies, D (2010). Origins and evolution of antibiotic resistance. Microbiology and Molecular Biology Reviews 74: 417433.
Dinsdale, EA, Edwards, RA, Hall, D, Angly, F, Breitbart, M, Brulc, JM, Furlan, M, Desnues, C, Haynes, M, Li, L, McDaniel, L, Moran, MA, Nelson, KE, Nilsson, C, Olson, R, Paul, J, Brito, BR, Ruan, Y, Swan, BK, Stevens, R, Valentine, DL, Thurber, RV, Wegley, L, White, BA and Rohwer, F (2008). Functional metagenomic profiling of nine biomes. Nature 452: 629632.
Dunny, GM (2007). The peptide pheromone-inducible conjugation system of Enterococcus faecalis plasmid pCF10: cell-cell signalling, gene transfer, complexity and evolution. Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 362: 11851193.
Dunny, GM (2013). Enterococcal sex pheromones: signaling, social behavior, and evolution. Annual Review of Genetics 47: 457482.
Durso, LM, Harhay, GP, Bono, JL and Smith, TP (2011). Virulence-associated and antibiotic resistance genes of microbial populations in cattle feces analyzed using a metagenomic approach. Journal of Microbiological Methods 84: 278282.
Erill, I, Campoy, S and Barbe, J (2007). Aeons of distress: an evolutionary perspective on the bacterial SOS response. FEMS Microbiology Reviews 31: 637656.
Feld, L, Schjorring, S, Hammer, K, Licht, TR, Danielsen, M, Krogfelt, K and Wilcks, A (2008). Selective pressure affects transfer and establishment of a Lactobacillus plantarum resistance plasmid in the gastrointestinal environment. Journal of Antimicrobial Chemotherapy 61: 845852.
Fisher, RA, Gollan, B and Helaine, S (2017). Persistent bacterial infections and persister cells. Nature Reviews: Microbiology 15: 453464.
Fuqua, WC, Winans, SC and Greenberg, EP (1994). Quorum sensing in bacteria: the LuxR-LuxI family of cell density-responsive transcriptional regulators. Journal of Bacteriology 176: 269275.
Garcia-Quintanilla, M, Ramos-Morales, F and Casadesus, J (2008). Conjugal transfer of the Salmonella enterica virulence plasmid in the mouse intestine. Journal of Bacteriology 190: 19221927.
Ghosh, TS, Gupta, SS, Nair, GB and Mande, SS (2013). In silico analysis of antibiotic resistance genes in the gut microflora of individuals from diverse geographies and age-groups. PLoS ONE 8: e83823.
Griffith, F (1928). The significance of pneumococcal types. Journal of Hygiene 27: 113159.
Harris, PN, Tambyah, PA and Paterson, DL (2015). Beta-lactam and beta-lactamase inhibitor combinations in the treatment of extended-spectrum beta-lactamase producing Enterobacteriaceae: time for a reappraisal in the era of few antibiotic options? Lancet Infectious Diseases 15: 475485.
Havarstein, LS, Coomaraswamy, G and Morrison, DA (1995). An unmodified heptadecapeptide pheromone induces competence for genetic transformation in Streptococcus pneumoniae. Proceedings of the National Academy of Sciences of the United States of America 92: 1114011144.
Heaton, MP and Handwerger, S (1995). Conjugative mobilization of a vancomycin resistance plasmid by a putative Enterococcus faecium sex pheromone response plasmid. Microbial Drug Resistance 1: 177183.
Hehemann, JH, Correc, G, Barbeyron, T, Helbert, W, Czjzek, M and Michel, G (2010). Transfer of carbohydrate-active enzymes from marine bacteria to Japanese gut microbiota. Nature 464: 908912.
Huddleston, JR (2014). Horizontal gene transfer in the human gastrointestinal tract: potential spread of antibiotic resistance genes. Infection and Drug Resistance 7: 167176.
Johnsborg, O, Eldholm, V and Havarstein, LS (2007). Natural genetic transformation: prevalence, mechanisms and function. Research in Microbiology 158: 767778.
Johnston, C, Martin, B, Fichant, G, Polard, P and Claverys, JP (2014). Bacterial transformation: distribution, shared mechanisms and divergent control. Nature Reviews: Microbiology 12: 181196.
Kim, JC, Chui, L, Wang, Y, Shen, J and Jeon, B (2016). Expansion of shiga toxin-producing Escherichia coli by use of bovine antibiotic growth promoters. Emerging Infectious Diseases 22: 802809.
Kortman, GA, Raffatellu, M, Swinkels, DW and Tjalsma, H (2014). Nutritional iron turned inside out: intestinal stress from a gut microbial perspective. FEMS Microbiology Reviews 38: 12021234.
Lambrecht, E, Bare, J, Chavatte, N, Bert, W, Sabbe, K and Houf, K (2015). Protozoan cysts act as a survival niche and protective shelter for foodborne pathogenic bacteria. Applied and Environmental Microbiology 81: 56045612.
Ley, RE, Peterson, DA and Gordon, JI (2006). Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell 124: 837848.
Liu, B and Pop, M (2009). ARDB – antibiotic resistance genes database. Nucleic Acids Research 37: D443D447.
Lorenz, MG and Wackernagel, W (1994). Bacterial gene transfer by natural genetic transformation in the environment. Microbiological Reviews 58: 563602.
Lurie-Weinberger, MN, Peeri, M and Gophna, U (2012). Contribution of lateral gene transfer to the gene repertoire of a gut-adapted methanogen. Genomics 99: 5258.
Lyte, M (2011). Probiotics function mechanistically as delivery vehicles for neuroactive compounds: microbial endocrinology in the design and use of probiotics. BioEssays 33: 574581.
Marshall, BM and Levy, SB (2011). Food animals and antimicrobials: impacts on human health. Clinical Microbiology Reviews 24: 718733.
Matic, I, Rayssiguier, C and Radman, M (1995). Interspecies gene exchange in bacteria: the role of SOS and mismatch repair systems in evolution of species. Cell 80: 507515.
McCuddin, ZP, Carlson, SA, Rasmussen, MA and Franklin, SK (2006). Klebsiella to Salmonella gene transfer within rumen protozoa: implications for antibiotic resistance and rumen defaunation. Veterinary Microbiology 114: 275284.
Michael, GB, Freitag, C, Wendlandt, S, Eidam, C, Fessler, AT, Lopes, GV, Kadlec, K and Schwarz, S (2015). Emerging issues in antimicrobial resistance of bacteria from food-producing animals. Future Microbiology 10: 427443.
Modi, SR, Lee, HH, Spina, CS and Collins, JJ (2013). Antibiotic treatment expands the resistance reservoir and ecological network of the phage metagenome. Nature 499: 219222.
Moliner, C, Fournier, PE and Raoult, D (2010). Genome analysis of microorganisms living in amoebae reveals a melting pot of evolution. FEMS Microbiology Reviews 34: 281294.
Ochman, H, Lawrence, JG and Groisman, EA (2000). Lateral gene transfer and the nature of bacterial innovation. Nature 405: 299304.
Olofsson, J, Axelsson-Olsson, D, Brudin, L, Olsen, B and Ellstrom, P (2013). Campylobacter jejuni actively invades the amoeba Acanthamoeba polyphaga and survives within non digestive vacuoles. PLoS ONE 8: e78873.
Palmer, BR and Marinus, MG (1994). The dam and dcm strains of Escherichia coli – a review. Gene 143: 112.
Pehrsson, EC, Forsberg, KJ, Gibson, MK, Ahmadi, S and Dantas, G (2013). Novel resistance functions uncovered using functional metagenomic investigations of resistance reservoirs. Frontiers in Microbiology 4: 145.
Peterson, G, Kumar, A, Gart, E and Narayanan, S (2011). Catecholamines increase conjugative gene transfer between enteric bacteria. Microbial Pathogenesis 51: 18.
Prudhomme, M, Attaiech, L, Sanchez, G, Martin, B and Claverys, JP (2006). Antibiotic stress induces genetic transformability in the human pathogen Streptococcus pneumoniae. Science 313: 8992.
Radman, M (1975). SOS repair hypothesis: phenomenology of an inducible DNA repair which is accompanied by mutagenesis. Basic Life Sciences 5A: 355367.
Salyers, AA, Gupta, A and Wang, Y (2004). Human intestinal bacteria as reservoirs for antibiotic resistance genes. Trends in Microbiology 12: 412416.
Schlacher, K and Goodman, MF (2007). Lessons from 50 years of SOS DNA-damage-induced mutagenesis. Nature Reviews: Molecular Cell Biology 8: 587594.
Schlundt, J, Saadbye, P, Lohmann, B, Jacobsen, BL and Nielsen, EM (1994). Conjugal transfer of plasmid DNA between Lactococcus lactis strains and distribution of transconjugants in the digestive tract of gnotobiotic rats. Microbial Ecology in Health and Disease 7: 5969.
Shterzer, N and Mizrahi, I (2015). The animal gut as a melting pot for horizontal gene transfer. Canadian Journal of Microbiology 61: 603605.
Smith, GR (1991). Conjugational recombination in E. coli: myths and mechanisms. Cell 64: 1927.
Smith, HO, Danner, DB and Deich, RA (1981). Genetic transformation. Annual Review of Biochemistry 50: 4168.
Sommer, MO, Dantas, G and Church, GM (2009). Functional characterization of the antibiotic resistance reservoir in the human microflora. Science 325: 11281131.
Sonnenburg, JL (2010). Microbiology: genetic pot luck. Nature 464: 837838.
Sun, D, Zhang, Y, Mei, Y, Jiang, H, Xie, Z, Liu, H, Chen, X and Shen, P (2006). Escherichia coli is naturally transformable in a novel transformation system. FEMS Microbiology Letters 265: 249255.
Szmolka, A and Nagy, B (2013). Multidrug resistant commensal Escherichia coli in animals and its impact for public health. Frontiers in Microbiology 4: 258.
Tezcan-Merdol, D, Ljungstrom, M, Winiecka-Krusnell, J, Linder, E, Engstrand, L and Rhen, M (2004). Uptake and replication of Salmonella enterica in Acanthamoeba rhysodes. Applied and Environmental Microbiology 70: 37063714.
Tomasz, A (1965). Control of the competent state in Pneumococcus by a hormone-like cell product: an example for a new type of regulatory mechanism in bacteria. Nature 208: 155159.
Ulrich, RL, Deshazer, D, Kenny, TA, Ulrich, MP, Moravusova, A, Opperman, T, Bavari, S, Bowlin, TL, Moir, DT and Panchal, RG (2013). Characterization of the Burkholderia thailandensis SOS response by using whole-transcriptome shotgun sequencing. Applied and Environmental Microbiology 79: 58305843.
Waldor, MK, Tschape, H and Mekalanos, JJ (1996). A new type of conjugative transposon encodes resistance to sulfamethoxazole, trimethoprim, and streptomycin in Vibrio cholerae O139. Journal of Bacteriology 178: 41574165.
Waters, CM and Bassler, BL (2005). Quorum sensing: cell-to-cell communication in bacteria. Annual Review of Cell and Developmental Biology 21: 319346.
Whitman, WB, Coleman, DC and Wiebe, WJ (1998). Prokaryotes: the unseen majority. Proceedings of the National Academy of Sciences of the USA 95: 65786583.
Wise, R (2002). Antimicrobial resistance: priorities for action. Journal of Antimicrobial Chemotherapy 49: 585586.
Wozniak, RA and Waldor, MK (2010). Integrative and conjugative elements: mosaic mobile genetic elements enabling dynamic lateral gene flow. Nature Reviews: Microbiology 8: 552563.
Zhu, YG, Johnson, TA, Su, JQ, Qiao, M, Guo, GX, Stedtfeld, RD, Hashsham, SA and Tiedje, JM (2013). Diverse and abundant antibiotic resistance genes in Chinese swine farms. Proceedings of the National Academy of Sciences of the USA 110: 34353440.


Factors influencing horizontal gene transfer in the intestine

  • Ximin Zeng (a1) and Jun Lin (a1)


Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed