Cited by 440Gut microbiota and healthOral microbiology and periodontitis researchMicrobial Community Ecology and Physiology

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Antibiotic perturbations to the gut microbiome

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Fishbein, Skye R. S., Mahmud, Bejan, Dantas, Gautam·2023·Nature Reviews Microbiology

DOI 10.1038/s41579-023-00933-yPMC PMC12087466

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Abstract

Antibiotic-mediated perturbation of the gut microbiome is associated with numerous infectious and autoimmune diseases of the gastrointestinal tract. Yet, as the gut microbiome is a complex ecological network of microorganisms, the effects of antibiotics can be highly variable. With the advent of multi-omic approaches for systems-level profiling of microbial communities, we are beginning to identify microbiome-intrinsic and microbiome-extrinsic factors that affect microbiome dynamics during antibiotic exposure and subsequent recovery. In this Review, we discuss factors that influence restructuring of the gut microbiome on antibiotic exposure. We present an overview of the currently complex picture of treatment-induced changes to the microbial community and highlight essential considerations for future investigations of antibiotic-specific outcomes. Finally, we provide a synopsis of available strategies to minimize antibiotic-induced damage or to restore the pretreatment architectures of the gut microbial community.

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Role of dietary fiber in the recovery of the human gut microbiome and its metabolome
Tanes, C., Bittinger, K. L., Gao, Y., Friedman, E. S., Nessel, L. A., Paladhi, U. R., Chau, L., Panfen, E., Fischbach, M. A., Braun, J. G., et al. (2021) · Cell Host & Microbe · doi:10.1016/j.chom.2020.12.012 · Cited by 325 · cited 1×
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Persistent metagenomic signatures of early-life hospitalization and antibiotic treatment in the infant gut microbiota and resistome
Gasparrini, A. J., Wang, B., Sun, X., Kennedy, E. A., Hernandez-Leyva, A. J., Ndao, I. M., Tarr, P. I., Warner, B. B., & Dantas, G. A. (2019) · Nature Microbiology · doi:10.1038/s41564-019-0550-2 · Cited by 320 · cited 2×
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Dietary fat intake and risk of cardiovascular disease and all-cause mortality in a population at high risk of cardiovascular disease
Guasch-Ferré, M., Babio, N., Martínez-González, M. A., Corella, D., Ros, E., Martín-Peláez, S., Estruch, R., Arós, F., Gómez-Gracia, E., Fiol, M., et al. (2015) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.115.116046 · Cited by 313 · cited 1×
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Minimizing treatment-induced emergence of antibiotic resistance in bacterial infections
Stracy, M., Snitser, O., Yelin, I., Amer, Y., Parizade, M., Katz, R., Rimler, G., Wolf, T., Herzel, E., Koren, G., et al. (2022) · Science · doi:10.1126/science.abg9868 · Cited by 311 · cited 1×
“Notably, the presence of ARG-encoding pathobionts in the gut is a risk factor for recurrent resistant infections post-treatment 30 .”
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Bile Acid Recognition by the Clostridium difficile Germinant Receptor, CspC, Is Important for Establishing Infection
Francis, M. B., Allen, C. A., Shrestha, R., & Sorg, J. A. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003356 · Cited by 303 · cited 1×
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Triclosan at environmentally relevant concentrations promotes horizontal transfer of multidrug resistance genes within and across bacterial genera
Lu, J., Wang, Y., Li, J., Mao, L., Nguyen, S. H., Duarte, T., Coin, L., Bond, P. L., Yuan, Z., & Guo, J. (2018) · Environment International · doi:10.1016/j.envint.2018.10.040 · Cited by 295 · cited 1×
“Increased rates of conjugation can result from the antibiotic-mediated induction of the bacterial SOS response and increased membrane permeability 153–157 , which may stem from the DNA damage inflicted by certain antibiotics.”
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Antibiotics as a selective driver for conjugation dynamics
Lopatkin, A. J., Huang, S., Smith, R. P., Srimani, J. K., Sysoeva, T. A., Bewick, S. A., Karig, D., & You, L. (2016) · Nature Microbiology · doi:10.1038/nmicrobiol.2016.44 · Cited by 288
What Antimicrobial Resistance Has Taught Us About Horizontal Gene Transfer
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Recovery of the Gut Microbiota after Antibiotics Depends on Host Diet, Community Context, and Environmental Reservoirs
Ng, K. M., Aranda-Díaz, A., Tropini, C., Frankel, M. R., Treuren, W. V., O’Loughlin, C. T., Merrill, B. D., Yu, F. B., Pruss, K. M., Oliveira, R. A., et al. (2019) · Cell Host & Microbe · doi:10.1016/j.chom.2019.10.011 · Cited by 279 · cited 2×
“Without fibre, mice with a conventional microbiome or a humanized microbiome have a delayed recovery in alpha diversity after ciprofloxacin treatment 96 .”
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Salmonella persisters promote the spread of antibiotic resistance plasmids in the gut
Bakkeren, E., Huisman, J. S., Fattinger, S. A., Hausmann, A., Furter, M., Egli, A., Slack, E. M. C., Sellin, M. E., Bonhoeffer, S., Regoes, R. R., et al. (2019) · Nature · doi:10.1038/s41586-019-1521-8 · Cited by 264 · cited 1×
“Apart from spore-mediated persistence, many gut microorganisms can tolerate antibiotics through various resiliency mechanisms, including persister cell formation, perhaps in a mucin-embedded biofilm or deeper tissue niche where they can resist antibiotics 84–87 .”
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Antibiotic use and the development of inflammatory bowel disease: a national case-control study in Sweden
Nguyen, L. H., Örtqvist, A. K., Cao, Y., Simon, T. G., Roelstraete, B., Song, M., Joshi, A. D., Staller, K. D., Chan, A. T., Khalili, H., et al. (2020) · The Lancet. Gastroenterology & hepatology · doi:10.1016/s2468-1253(20)30267-3 · Cited by 256 · cited 2×
“…and metabolic pathway architecture of the gut microbial community (referred to as dysbiosis) have been associated with an increased risk of numerous human pathologies, including inflammatory bowel disease 5 , obesity 6 , colorectal cancer 7,8 and numerous gastrointestinal infections 9–11 .”
BackgroundInfluential
Probiotics impact the antibiotic resistance gene reservoir along the human GI tract in a person-specific and antibiotic-dependent manner
Montassier, E., Valdés-Mas, R., Batard, E., Zmora, N., Dori-Bachash, M., Suez, J., & Elinav, E. (2021) · Nature Microbiology · doi:10.1038/s41564-021-00920-0 · Cited by 256
Transmission of human-associated microbiota along family and social networks
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“those incorporating long-read metagenomic sequencing, can provide increased strain-level resolution 70–72 .”
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On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of B. influenzae. 1929.
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A review of the role of antibiotic policies in the control of antibiotic resistance
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“…a greater understanding of the mechanisms by which antibiotics perturb the human microbiome is critical to maximizing the therapeutic benefits of these agents while reducing both the damage imposed on the commensal gut microbiome and the broader spread of antimicrobial resistant pathogens 23,24 .”
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Acute and persistent effects of commonly used antibiotics on the gut microbiome and resistome in healthy adults
Anthony, W., Wang, B., Sukhum, K. V., D’Souza, A. W., Hink, T., Cass, C., Seiler, S. M., Reske, K. A., Coon, C., Dubberke, E. R., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110649 · Cited by 240 · cited 7×
“Antibiotics expectedly enrich for ARGs that confer resistance to the treatment agent 33,34,51,62–66 ,114,115, 117, 119– 123 through selection of bacterial strains Importantly, the effects of antibiotics on the gut resistome vary substantially depending on the nature of the administered drug…”
BackgroundInfluentialSelf-citation
Microbiota-accessible carbohydrates suppress Clostridium difficile infection in a murine model
Hryckowian, A. J., Treuren, W. V., Smits, S. A., Davis, N. M., Gardner, J. O., Bouley, D. M., & Sonnenburg, J. L. (2018) · Nature Microbiology · doi:10.1038/s41564-018-0150-6 · Cited by 239 · cited 1×
“…can be used to restore the production of these molecules; this restoration is largely associated with colonization resistance against pathogens 49,177,178 or prebiotic administration, which may facilitate the growth of commensal members of the microbiome and/or prevent the colonization of…”
Multimodal interactions of drugs, natural compounds and pollutants with the gut microbiota
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“The interactions between these non-antibiotic factors and the microbiome have been reviewed elsewhere 109 .”
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Antibiotic-induced replication stress triggers bacterial competence by increasing gene dosage near the origin
Slager, J., Kjos, M., Attaiech, L., & Veening, J.-W. (2014) · Cell · doi:10.1016/j.cell.2014.01.068 · Cited by 237
Clusters of Antibiotic Resistance Genes Enriched Together Stay Together in Swine Agriculture
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Gut microbiome alterations in high-fat-diet-fed mice are associated with antibiotic tolerance
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The distribution of antibiotic use and its association with antibiotic resistance
Olesen, S. W., Barnett, M. L., MacFadden, D. R., Brownstein, J. S., Hernández–Dı́az, S., Lipsitch, M., & Grad, Y. H. (2018) · eLife · doi:10.7554/elife.39435 · Cited by 227
Global transcriptional control by glucose and carbon regulator CcpA in Clostridium difficile
Antunes, A., Camiade, É., Monot, M., Courtois, E., Barbut, F., Sernova, N. V., Rodionov, D. A., Martin‐Verstraete, I., & Dupuy, B. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks864 · Cited by 222
Widespread transfer of mobile antibiotic resistance genes within individual gut microbiomes revealed through bacterial Hi-C
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“These limitations can be addressed through Hi-C, a technique in which crosslinking before cell lysis preserves interacting DNA molecules and the information regarding the MGE–bacterial host associations 138 .”
BackgroundMethodInfluential
Antibiotic Administration Routes Significantly Influence the Levels of Antibiotic Resistance in Gut Microbiota
Zhang, L., Huang, Y., Zhou, Y., Buckley, T., & Wang, H. H. (2013) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00670-13 · Cited by 203
Metabolism of Bile Salts in Mice Influences Spore Germination in Clostridium difficile
Giel, J. L., Sorg, J. A., Sonenshein, A. L., & Zhu, J. (2010) · PLoS ONE · doi:10.1371/journal.pone.0008740 · Cited by 202
Inhibiting Growth of Clostridioides difficile by Restoring Valerate, Produced by the Intestinal Microbiota
McDonald, J. A. K., Mullish, B. H., Pechlivanis, A., Liu, Z., Brignardello, J., Kao, D. H., Holmes, E. C., Li, J. V., Clarke, T. B., Thursz, M. R., et al. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.07.014 · Cited by 200 · cited 1×
“…be used to restore the production of these molecules; this restoration is largely associated with colonization resistance against pathogens 49,177,178 or prebiotic administration, which may facilitate the growth of commensal members of the microbiome and/or prevent the colonization of pathogenic…”
Method
Necrotizing enterocolitis is preceded by increased gut bacterial replication, Klebsiella , and fimbriae-encoding bacteria
Olm, M. R., Bhattacharya, N., Crits‐Christoph, A., Firek, B., Baker, R. W., Song, Y. S., Morowitz, M. J., & Banfield, J. F. (2019) · Science Advances · doi:10.1126/sciadv.aax5727 · Cited by 195
Strain-level characterization of broad host range mobile genetic elements transferring antibiotic resistance from the human microbiome
Forster, S. C., Liu, J., Kumar, N., Gulliver, E. L., Gould, J. A., Escobar‐Zepeda, A., Mkandawire, T. T., Pike, L. J., Shao, Y., Stares, M., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-29096-9 · Cited by 191 · cited 1×
“However, the spread of ARGs is not exclusively attributed to their primary bacterial hosts: ARGs are commonly encoded within mobile genetic elements (MGEs) 28 , which enable their acquisition by new hosts, including pathobionts 29 .”
Background
THE TREASURE CALLED ANTIBIOTICS.
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High-Fat Diet and Antibiotics Cooperatively Impair Mitochondrial Bioenergetics to Trigger Dysbiosis that Exacerbates Pre-inflammatory Bowel Disease
Lee, J., Cevallos, S. A., Byndloss, M. X., Tiffany, C. R., Olsan, E. E., Butler, B. P., Young, B. M., Rogers, A. W. L., Nguyen, H., Kim, K., et al. (2020) · Cell Host & Microbe · doi:10.1016/j.chom.2020.06.001 · Cited by 189 · cited 1×
“Antibiotic treatment of mice on a high-fat diet pro-vokes pathological inflammation at the gut mucosa and increased levels of Enterobacterales, a taxonomic order that contains common pathobionts of the microbiome 105 .”
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An assay for determining minimal concentrations of antibiotics that drive horizontal transfer of resistance
Jutkina, J., Rutgersson, C., Flach, C., & Larsson, D. G. J. (2016) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2016.01.044 · Cited by 186
Antibiotic-Induced Disruption of Gut Microbiota Alters Local Metabolomes and Immune Responses
Sun, L., Zhang, X., Zhang, Y., Zheng, K., Xiang, Q., Chen, N., Chen, Z., Zhang, N., Zhu, J., & He, Q. (2019) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2019.00099 · Cited by 186
Salmonella typhimurium intercepts Escherichia coli signaling to enhance antibiotic tolerance
Vega, N. M., Allison, K. R., Samuels, A. N., Klempner, M. S., & Collins, J. J. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1308085110 · Cited by 185
Probiotics interaction with foodborne pathogens: a potential alternative to antibiotics and future challenges
Wan, M. L. Y., Forsythe, S. J., & El-Nezami, H. S. (2018) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2018.1490885 · Cited by 185 · cited 2×
“Nonetheless, probiotic organisms have been extensively used therapeutically against various pathogens, commonly achieving their native anti-infective activity through competitive exclusion, sequestration and release of antimicrobial compounds (constitutive or induced), as reviewed elsewhere 166 .”
Background
Macrolide and Nonmacrolide Resistance with Mass Azithromycin Distribution
Doan, T. A., Worden, L., Hinterwirth, A. J., Arzika, A. M., Maliki, R., Abdou, A., Zhong, L., Chen, C., Cook, C. A., Lebas, E., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2002606 · Cited by 185
Genomic insights into the 2016–2017 cholera epidemic in Yemen
Weill, F., Domman, D., Njamkepo, E., Almesbahi, A. A., Naji, M., Nasher, S. S., Rakesh, A., Assiri, A. M., Sharma, N. C., Kariuki, S., et al. (2018) · Nature · doi:10.1038/s41586-018-0818-3 · Cited by 182 · cited 1×
“Although clinical studies of bacterial infections often emphasize the species and/or strain of opportunistic pathogens or pathobionts 53,54 , literature describing commensal fluctuations during antibiotic exposure is currently limited to the taxonomic resolution of genus or species.”
Background
The Gut Microbiome as a Reservoir for Antimicrobial Resistance
Anthony, W., Burnham, C. D., Dantas, G. A., & Kwon, J. H. (2020) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiaa497 · Cited by 177 · cited 1×
“17)), including drug-resistant Enterobacteriaceae, Clostridioides difficile , vancomycin-resistant Enterococcus and Salmonella spp., are responsible for a substantial amount of gastrointestinal disease 18 .”
BackgroundSelf-citation
Clindamycin-induced enrichment and long-term persistence of resistant Bacteroides spp. and resistance genes
Löfmark, S., Jernberg, C., Jansson, J. K., & Edlund, C. (2006) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkl420 · Cited by 175
Antibiotic effects on gut microbiota and metabolism are host dependent
Fujisaka, S., Ussar, S., Clish, C. B., Devkota, S., Dreyfuss, J. M., Sakaguchi, M., Soto, M., Konishi, M., Softic, S., Altındiş, E., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci86674 · Cited by 171
Antibiotic-induced decreases in the levels of microbial-derived short-chain fatty acids correlate with increased gastrointestinal colonization of Candida albicans
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“…can be used to restore the production of these molecules; this restoration is largely associated with colonization resistance against pathogens 49,177,178 or prebiotic administration, which may facilitate the growth of commensal members of the microbiome and/or prevent the colonization of…”
Protection of the Human Gut Microbiome From Antibiotics
de Gunzburg, J., Ghozlane, A., Ducher, A., Chatelier, E. L., Duval, X., Ruppé, É., Armand-Lefèvre, L., Sablier-Gallis, F., Burdet, C., Alavoine, L., et al. (2017) · The Journal of Infectious Diseases · doi:10.1093/infdis/jix604 · Cited by 166
Distinct impact of antibiotics on the gut microbiome and resistome: a longitudinal multicenter cohort study
Willmann, M., Vehreschild, M. J. G. T., Biehl, L. M., Vogel, W., Dörfel, D., Hamprecht, A. G., Seifert, H., Autenrieth, I. B., & Peter, S. (2019) · BMC Biology · doi:10.1186/s12915-019-0692-y · Cited by 166 · cited 6×
“Recent investigations of the gut resistome have primarily relied on whole-metagenome shotgun sequencing with subsequent alignment of sequencing reads or annotated open reading frames from assembled contigs against one or a few of the available databases of known ARGs 32–34 ,59 ,62 ,114, 117– 119”
BackgroundMethodInfluential
Efficacy of Hospital Cleaning Agents and Germicides Against EpidemicClostridium difficileStrains
Fawley, W. N., Underwood, S., Freeman, J., Baines, S. D., Saxton, K., Stephenson, K., Owens, R. C., & Wilcox, M. H. (2007) · Infection Control and Hospital Epidemiology · doi:10.1086/519201 · Cited by 165
Effect of various antibiotics on modulation of intestinal microbiota and bile acid profile in mice
Zhang, Y., Limaye, P. B., Renaud, H. J., & Klaassen, C. D. (2014) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2014.03.009 · Cited by 162
Impact of microbial derived secondary bile acids on colonization resistance against Clostridium difficile in the gastrointestinal tract
Winston, J. A., & Theriot, C. M. (2016) · Anaerobe · doi:10.1016/j.anaerobe.2016.05.003 · Cited by 155
Metagenome-assembled genome binning methods with short reads disproportionately fail for plasmids and genomic islands
Maguire, F., Jia, B., Gray, K. L., Lau, W. Y. V., Beiko, R. G., & Brinkman, F. S. L. (2020) · Microbial Genomics · doi:10.1099/mgen.0.000436 · Cited by 152
Metagenomic analysis with strain-level resolution reveals fine-scale variation in the human pregnancy microbiomePreprint
Goltsman, D. S. A., Sun, C. L., Proctor, D. M., DiGiulio, D. B., Robaczewska, A., Thomas, B. C., Shaw, G. M., Stevenson, D. K., Holmes, S., Banfield, J. F., et al. (2018) · Genome Research · doi:10.1101/gr.236000.118 · Cited by 149 · cited 1×
“those incorporating long-read metagenomic sequencing, can provide increased strain-level resolution 70–72 .”
Background
Diet, microbes, and host genetics: the perfect storm in inflammatory bowel diseases
Leone, V., Chang, E. B., & Devkota, S. (2013) · Journal of Gastroenterology · doi:10.1007/s00535-013-0777-2 · Cited by 147 · cited 1×
“Investigations into ‘Western-style’ diets (high in fat and simple sugars) have revealed that these diets correlate with an increased risk for obesity and heart disease, among other poor health outcomes 103,104 .”
Background
Collateral damage from oral ciprofloxacin versus nitrofurantoin in outpatients with urinary tract infections: a culture-free analysis of gut microbiota
Stewardson, A. J., Gaïa, N., François, P., Malhotra-Kumar, S., Delémont, C., de Tejada, B. M., Schrenzel, J., Harbarth, S., & Lazarević, V. (2014) · Clinical Microbiology and Infection · doi:10.1016/j.cmi.2014.11.016 · Cited by 147 · cited 1×
“…and nitrofurantoin, ciprofloxacin has been shown to cause a greater reduction in species richness (less than twofold) and beta diversity 58,59 , in addition to its effect in depleting Bifidobacterium and Ruminococcus spp. Azithromycin has been widely explored (in clinical trials of…”
Background
Cross-feeding modulates antibiotic tolerance in bacterial communities
Adamowicz, E. M., Flynn, J. M., Hunter, R. C., & Harcombe, W. R. (2018) · The ISME Journal · doi:10.1038/s41396-018-0212-z · Cited by 145 · cited 1×
“In vitro studies of interactions between two gut commensals during antibiotic treatment indicate that symbiotic relationships can have multiple outcomes in effecting differences in antibiotic tolerance in one 99 or both members of the community 100,101 .”
Background
Colonization of the live biotherapeutic product VE303 and modulation of the microbiota and metabolites in healthy volunteers
Dsouza, M., Menon, R., Crossette, E. M., Bhattarai, S. K., Schneider, J., Kim, Y., Reddy, S., Caballero, S., Felix, C. R., Cornacchione, L. P., et al. (2022) · Cell Host & Microbe · doi:10.1016/j.chom.2022.03.016 · Cited by 142 · cited 2×
“…Biosciences), is composed of fewer members than SER-109 and demonstrates robust restoration of butyrate production and secondary bile acid production in dysbiotic human microbiomes engrafted into mice; this community is well tolerated when administered with vancomycin to healthy volunteers 189 .”
Background
Antibiotic use during pregnancy alters the commensal vaginal microbiota
Stokholm, J., Schjørring, S., Eskildsen, C. E., Pedersen, L., Bischoff, A. L., Følsgaard, N. V., Carson, C. G., Chawes, B., Bønnelykke, K., Mølgaard, A., et al. (2013) · Clinical Microbiology and Infection · doi:10.1111/1469-0691.12411 · Cited by 139
Transfer of Carbapenem-Resistant Plasmid fromKlebsiella pneumoniaeST258 toEscherichia coliin Patient
Goren, M. G., Carmeli, Y., Schwaber, M. J., Chmelnitsky, I., Schechner, V., & Navon‐Venezia, S. (2010) · Emerging infectious diseases · doi:10.3201/eid1606.091671 · Cited by 138
Engineered Probiotic for the Inhibition of Salmonella via Tetrathionate-Induced Production of Microcin H47
Palmer, J. D., Piattelli, E., McCormick, B. A., Silby, M. W., Brigham, C. J., & Bucci, V. (2018) · ACS Infectious Diseases · doi:10.1021/acsinfecdis.7b00114 · Cited by 133
Clinical Relevance of Macrolide-Resistant Streptococcus pneumoniae for Community-Acquired Pneumonia
Lynch, J. P., & Martínez, F. J. (2002) · Clinical Infectious Diseases · doi:10.1086/324527 · Cited by 132 · cited 1×
“…and metabolic pathway architecture of the gut microbial community (referred to as dysbiosis) have been associated with an increased risk of numerous human pathologies, including inflammatory bowel disease 5 , obesity 6 , colorectal cancer 7,8 and numerous gastrointestinal infections 9–11 .”
Background
Antibiotic perturbation of the preterm infant gut microbiome and resistome
Gasparrini, A. J., Crofts, T. S., Gibson, M. K., Tarr, P. I., Warner, B. B., & Dantas, G. A. (2016) · Gut Microbes · doi:10.1080/19490976.2016.1218584 · Cited by 132 · cited 1×
“Enrichment for AMR often begins within the gut microbiome of the patient, with antibiotics increasing the abundance of resident bacteria that carry antibiotic resistance genes (ARGs) and altering ARG content within the gut microbiome (termed the ‘resistome’) 26,27 .”
BackgroundSelf-citation
Gut microbiome alteration in MORDOR I: a community-randomized trial of mass azithromycin distribution
Doan, T. A., Hinterwirth, A. J., Worden, L., Arzika, A. M., Maliki, R., Abdou, A., Kane, S., Zhong, L., Cummings, M. E., Sakar, S., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0533-0 · Cited by 132
Microbial Metabolism Modulates Antibiotic Susceptibility within the Murine Gut Microbiome
Cabral, D. J., Penumutchu, S., Reinhart, E. M., Zhang, C., Korry, B. J., Wurster, J. I., Nilson, R., Guang, A., Sano, W. H., Rowan-Nash, A. D., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.08.020 · Cited by 132 · cited 2×
“Antibiotic susceptibility of a gut commensal may thus be determined by its surrounding nutrient milieu (Box 1), a concept that remains difficult to investigate in vivo 88–92 .”
Background
Induction of competence for genetic transformation by antibiotics: convergent evolution of stress responses in distant bacterial species lacking SOS?
Charpentier, X., Polard, P., & Claverys, J. (2012) · Current Opinion in Microbiology · doi:10.1016/j.mib.2012.08.001 · Cited by 129 · cited 1×
“Antibiotics can reportedly facilitate all three mechanisms of HGT: transformation 141–143 , transduction 144 and conjugation 145,146 , the last being the best-studied form of horizontal transfer of ARGs 138,147–152 (Box 2).”
Background
Antimicrobial Probiotics Reduce Salmonella enterica in Turkey Gastrointestinal Tracts
Forkus, B., Ritter, S. C., Vlysidis, M., Geldart, K., & Kaznessis, Y. N. (2017) · Scientific Reports · doi:10.1038/srep40695 · Cited by 128 · cited 1×
“Probiotics can also be engineered to express and release pathogen-specific antimicrobial agents 201 .”
Background
Cephalosporinases associated with outer membrane vesicles released by Bacteroides spp. protect gut pathogens and commensals against β-lactam antibiotics
Stentz, R., Horn, N., Cross, K. L., Salt, L. J., Brearley, C. A., Livermore, D. M., & Carding, S. R. (2014) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dku466 · Cited by 124 · cited 1×
“As proof of principle, gut commensal Bacteroides spp. can release cephalosporinases that protect susceptible members of the community from lethal doses of cefotaxime 171 .”
Background
Maternal propensity for infections and risk of childhood asthma: a registry-based cohort study
Stokholm, J., Sevelsted, A., Bønnelykke, K., & Bisgaard, H. F. (2014) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(14)70152-3 · Cited by 120
Comparison of different modes of antibiotic delivery on gut microbiota depletion efficiency and body composition in mouse
Tirelle, P., Breton, J., Riou, G., Déchelotte, P., Coëffier, M., & Ribet, D. (2020) · BMC Microbiology · doi:10.1186/s12866-020-02018-9 · Cited by 116
Engineering probiotics to inhibit Clostridioides difficile infection by dynamic regulation of intestinal metabolism
Koh, E., Hwang, I. Y., Lee, H. L., Sotto, R. D., Lee, J. W. J., Lee, Y. S., March, J. C., & Chang, M. W. (2022) · Nature Communications · doi:10.1038/s41467-022-31334-z · Cited by 116 · cited 5×
“The engineered probiotic reduced the germination of C. difficile endospores, resulting in 100% survival and improved clinical symptoms in murine models of C. difficile infection 168 .”
BackgroundInfluential
Mucus-degrading Bacteroides link carbapenems to aggravated graft-versus-host disease
Hayase, E., Hayase, T., Jamal, M. A., Miyama, T., Chang, C., Ortega, M. R., Ahmed, S., Karmouch, J. L., Sanchez, C. A., Brown, A. N., et al. (2022) · Cell · doi:10.1016/j.cell.2022.09.007 · Cited by 116 · cited 1×
“In addition to enrichment of overtly pathogenic organisms following antibiotic exposure, antibiotics are increasingly considered key contributors to more complex immunological manifestations such as graft-versus-host disease, inflammatory bowel disease and even allergies in the host 5,19–21 .”
BackgroundInfluential
Macrolide Resistance in MORDOR I — A Cluster-Randomized Trial in Niger
Doan, T. A., Arzika, A. M., Hinterwirth, A. J., Maliki, R., Zhong, L., Cummings, S., Sarkar, S., Chen, C., Porco, T. C., Keenan, J. D., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmc1901535 · Cited by 115
Selective pressure affects transfer and establishment of a Lactobacillus plantarum resistance plasmid in the gastrointestinal environment
Feld, L., Schjørring, S., Hammer, K., Licht, T. R., Danielsen, M., Krogfelt, K. A., & Wilcks, A. (2008) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkn033 · Cited by 112 · cited 1×
“However, the effects of antibiotics on the rates of HGT (particularly conjugation) are contested, with other studies demonstrating highest plasmid transfer rates in the absence of antibiotics 158–161 .”
Result
Gut Bacterial Microbiota and its Resistome Rapidly Recover to Basal State Levels after Short-term Amoxicillin-Clavulanic Acid Treatment in Healthy Adults
MacPherson, C. W., Mathieu, O., Tremblay, J., Champagne, J., Nantel, A., Girard, S., & Tompkins, T. A. (2018) · Scientific Reports · doi:10.1038/s41598-018-29229-5 · Cited by 110 · cited 3×
“…antibiotic treatment in adult humans is often associated with an increase in the relative abundance of facultative anaerobes that were initially less abundant members of the community, such as Enterobacteriaceae, Enterococcus spp., Clostridium spp. and Streptococcus spp. 34,37,51,52 .”
Background
Inter-species interactions alter antibiotic efficacy in bacterial communities
Bottery, M. J., Matthews, J. L., Wood, A. J., Johansen, H. K., Pitchford, J. W., & Friman, V. (2021) · The ISME Journal · doi:10.1038/s41396-021-01130-6 · Cited by 109
Ecology determines how low antibiotic concentration impacts community composition and horizontal transfer of resistance genes
Cairns, J., Ruokolainen, L., Hultman, J., Tamminen, M. V., Virta, M., & Hiltunen, T. (2018) · Communications Biology · doi:10.1038/s42003-018-0041-7 · Cited by 108 · cited 2×
“Low doses of antibiotics have been reported to facilitate plasmid conjugation within bacterial communities 145,146 .”
Background
Machine Learning Leveraging Genomes from Metagenomes Identifies Influential Antibiotic Resistance Genes in the Infant Gut Microbiome
Rahman, S. F., Olm, M. R., Morowitz, M. J., & Banfield, J. F. (2018) · mSystems · doi:10.1128/msystems.00123-17 · Cited by 105
Platforms for elucidating antibiotic resistance in single genomes and complex metagenomes
Gupta, C. L., Tiwari, R. K., & Cytryn, E. J. (2020) · Environment International · doi:10.1016/j.envint.2020.105667 · Cited by 105
The Role of Antibiotic Resistance Genes in the Fitness Cost of Multiresistance Plasmids
Rajer, F., & Sandegren, L. (2022) · mBio · doi:10.1128/mbio.03552-21 · Cited by 104
An engineered live biotherapeutic for the prevention of antibiotic-induced dysbiosis
Cubillos-Ruiz, A., Alcantar, M. A., Donghia, N. M., Cárdenas, P., Ávila-Pacheco, J., & Collins, J. J. (2022) · Nature Biomedical Engineering · doi:10.1038/s41551-022-00871-9 · Cited by 104 · cited 15×
“Such increased HGT rates are of concern owing to their potential implication in the spread of ARGs to both resident commensals and pathobionts within the gut microbiome 140 , thus increasing the future risk of opportunistic infections.”
BackgroundInfluential
Effects of selective digestive decontamination (SDD) on the gut resistome
Buelow, E., Gonzalez, T. D. J. B., Versluis, D., Oostdijk, E. A. N., Ogilvie, L. A., van Mourik, M. S. M., Oosterink, E., van Passel, M. W. J., Smidt, H., D’Andrea, M. M., et al. (2014) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dku092 · Cited by 103 · cited 1×
“As we have outlined here, the gut microbiome response to antibiotics is highly complex and variable 33 , driven by a multitude of factors 33,59,206,207 .”
Background
Receptor-targeted engineered probiotics mitigate lethal Listeria infection
Drolia, R., Amalaradjou, M. A. R., Ryan, V., Tenguria, S., Liu, D., Bai, X., Xu, L., Singh, A. K., Cox, A. D., Bernal-Crespo, V., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-20200-5 · Cited by 103
Effects of Probiotic Supplementation on the Gut Microbiota and Antibiotic Resistome Development in Preterm Infants
Esaiassen, E., Hjerde, E., Cavanagh, J. P., Pedersen, T., Andresen, J. H., Rettedal, S. I., Støen, R., Nakstad, B., Willassen, N. P., & Klingenberg, C. (2018) · Frontiers in Pediatrics · doi:10.3389/fped.2018.00347 · Cited by 102
Mucin-derived O -glycans supplemented to diet mitigate diverse microbiota perturbations
Pruss, K. M., Marcobal, A. M., Southwick, A. M., Dahan, D., Smits, S. A., Ferreyra, J. A., Higginbottom, S. K., Sonnenburg, E. D., Kashyap, P., Choudhury, B., et al. (2020) · The ISME Journal · doi:10.1038/s41396-020-00798-6 · Cited by 101
Critical evaluation of short, long, and hybrid assembly for contextual analysis of antibiotic resistance genes in complex environmental metagenomes
Brown, C., Keenum, I. M., Dai, D., Zhang, L., Vikesland, P. J., & Pruden, A. J. (2021) · Scientific Reports · doi:10.1038/s41598-021-83081-8 · Cited by 100 · cited 4×
“The longer contigs also reveal the genetic context of ARGs and their potential localization within MGEs 151 .”
BackgroundInfluential
Changes in the life history traits of Daphnia magna are associated with the gut microbiota composition shaped by diet and antibiotics
Akbar, S., Gu, L., Sun, Y., Zhou, Q., Zhang, L., Lyu, K., Huang, Y., & Yang, Z. (2019) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2019.135827 · Cited by 98
Shiga Toxin–Producing Escherichia coli Transmission via Fecal Microbiota Transplant
Zellmer, C., Sater, M. R. A., Huntley, M. H., Osman, M., Olesen, S. W., & Ramakrishna, B. (2021) · Clinical Infectious Diseases · doi:10.1093/cid/ciaa1486 · Cited by 98
Antibiotics as Instigators of Microbial Dysbiosis: Implications for Asthma and Allergy
Wypych, T. P., & Marsland, B. J. (2018) · Trends in Immunology · doi:10.1016/j.it.2018.02.008 · Cited by 97
Consolidating and Exploring Antibiotic Resistance Gene Data Resources
Xavier, B. B., Das, A. J., Cochrane, G., Ganck, S. D., Kumar‐Singh, S., Aarestrup, F. M., Goossens, H., & Malhotra‐Kumar, S. (2016) · Journal of Clinical Microbiology · doi:10.1128/jcm.02717-15 · Cited by 96 · cited 1×
“There are instances of the same gene annotated by different names across databases 133 , which further impedes accurate comparative analysis of corresponding resistome studies.”
Background
Predominantly Antibiotic-resistant Intestinal Microbiome Persists in Patients With Pouchitis Who Respond to Antibiotic Therapy
Dubinsky, V., Reshef, L., Bar, N., Keizer, D., Golan, N., Rabinowitz, K. M., Godny, L., Yadgar, K., Zonensain, K., Tulchinsky, H., et al. (2019) · Gastroenterology · doi:10.1053/j.gastro.2019.10.001 · Cited by 96 · cited 4×
“…by significant decreases in the relative abundance of important members of the phyla Firmicutes, Bacteroidetes and Actinobacteria, most notably Faecalibacterium prausnitzii , Eubacterium spp., Roseburia spp., Bifidobacterium spp., Dorea spp., Anaerostipes spp. and Ruminococcus spp. 32,34,38,39 .”
BackgroundMethodInfluential
Review and Comparison of Antimicrobial Resistance Gene Databases
Papp, M., & Solymosi, N. (2022) · Antibiotics · doi:10.3390/antibiotics11030339 · Cited by 96
Baseline microbiota composition modulates antibiotic-mediated effects on the gut microbiota and host
Lavelle, A., Hoffmann, T. W., Pham, H., Langella, P., Guédon, É., & Sokol, H. (2019) · Microbiome · doi:10.1186/s40168-019-0725-3 · Cited by 93
Systemic absorption of oral vancomycin in patients with Clostridium difficile infection
Rao, S., Kupfer, Y. Y., Pagala, M. K. D., Chapnick, E. K., & Tessler, S. (2011) · Scandinavian Journal of Infectious Diseases · doi:10.3109/00365548.2010.544671 · Cited by 92
Effects of stress and other environmental factors on horizontal plasmid transfer assessed by direct quantification of discrete transfer events
Johnsen, A. R., & Kroer, N. (2006) · FEMS Microbiology Ecology · doi:10.1111/j.1574-6941.2006.00230.x · Cited by 91
Combined treatment with the antibiotics kanamycin and streptomycin promotes the conjugation ofEscherichia coli
Zhang, P.-Y., Xu, P., Xia, Z., Wang, J., Xiong, J., & Li, Y. (2013) · FEMS Microbiology Letters · doi:10.1111/1574-6968.12282 · Cited by 89
Use of ribaxamase (SYN-004), a β-lactamase, to prevent Clostridium difficile infection in β-lactam-treated patients: a double-blind, phase 2b, randomised placebo-controlled trial
Kokai‐Kun, J. F., Roberts, T., Coughlin, O., Le, C., Whalen, H., Stevenson, R. W., Wacher, V. J., & Sliman, J. A. (2019) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(18)30731-x · Cited by 89 · cited 1×
“Similarly, oral administration of a β-lactamase concurrently with systemic β-lactam antibiotic treatment maintains the taxonomic structure of the gut community 164,172 .”
Background
Dosing a synbiotic of human milk oligosaccharides and B. infantis leads to reversible engraftment in healthy adult microbiomes without antibiotics
Button, J. E., Autran, C. A., Reens, A. L., Cosetta, C. M., Smriga, S., Ericson, M. E., Pierce, J. V., Cook, D. N., Lee, M. L., Sun, A. K., et al. (2022) · Cell Host & Microbe · doi:10.1016/j.chom.2022.04.001 · Cited by 86
Surveying Gut Microbiome Research in Africans: Toward Improved Diversity and Representation
Brewster, R., Tamburini, F. B., Asiimwe, E., Oduaran, O. H., Hazelhurst, S., & Bhatt, A. S. (2019) · Trends in Microbiology · doi:10.1016/j.tim.2019.05.006 · Cited by 85 · cited 1×
“Thus, our current models of microbiome dynamics are critically limited in their scope and application 209 .”
Method
Biofilms harbour Clostridioides difficile, serving as a reservoir for recurrent infection
Normington, C., Moura, I. B., Bryant, J. A., Ewin, D. J., Clark, E., Kettle, M. J., Harris, H. C., Spittal, W. D., Davis, G. L., Henn, M. R., et al. (2021) · npj Biofilms and Microbiomes · doi:10.1038/s41522-021-00184-w · Cited by 84 · cited 1×
“These spores survive antibiotic exposure in the gastrointestinal tract, and the presence of free nutrients and primary bile acids (as discussed above) provides molecular signals for spore germination and subsequent pathogenesis 82,83 .”
Background
Dissecting the effects of antibiotics on horizontal gene transfer: analysis suggests a critical role of selection dynamics
Lopatkin, A. J., Sysoeva, T. A., & You, L. (2016) · BioEssays · doi:10.1002/bies.201600133 · Cited by 83 · cited 1×
“3), which suggests that the reported post-antibiotic enrichments of ARG-encoding MGEs often result from the growth advantage conferred on transconjugants, not higher HGT rates per se 162 .”
Background
Durable reduction of Clostridioides difficile infection recurrence and microbiome restoration after treatment with RBX2660: results from an open-label phase 2 clinical trial
Orenstein, R., Dubberke, E. R., Khanna, S., Lee, C., Yoho, D. S., Johnson, S., Hecht, G. A., DuPont, H. L., Gerding, D. N., Blount, K., et al. (2022) · BMC Infectious Diseases · doi:10.1186/s12879-022-07256-y · Cited by 83 · cited 1×
“In the context of rCDI, several microbial communities (derived from human donor stool or from defined bacterial culture) have shown promise in providing decreased risk of recurrent episodes 186–189 .”
Background
The effect of a microbial ecosystem therapeutic (MET-2) on recurrent Clostridioides difficile infection: a phase 1, open-label, single-group trial
Kao, D., Wong, K., Franz, R., Cochrane, K., Sherriff, K., Chui, L., Lloyd, C., Roach, B., Bai, A. D., Petrof, E. O., et al. (2021) · The Lancet Gastroenterology & Hepatology · doi:10.1016/s2468-1253(21)00007-8 · Cited by 81
Activity of vancomycin against epidemic Clostridium difficile strains in a human gut model
Baines, S. D., O'Connor, R., Saxton, K., Freeman, J., & Wilcox, M. H. (2008) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkn502 · Cited by 79
Spatial analysis of gut microbiome reveals a distinct ecological niche associated with the mucus layer
Duncan, K., Carey-Ewend, K., & Vaishnava, S. (2021) · Gut Microbes · doi:10.1080/19490976.2021.1874815 · Cited by 79
Antibiotic Treatment Drives the Diversification of the Human Gut Resistome
Li, J., Rettedal, E. A., van der Helm, E., Ellabaan, M. M. H., Panagiotou, G., & Sommer, M. O. A. (2019) · Genomics Proteomics & Bioinformatics · doi:10.1016/j.gpb.2018.12.003 · Cited by 78
Repurposing a Two-Component System-Based Biosensor for the Killing of Vibrio cholerae
Jayaraman, P., Holowko, M. B., Yeoh, J. W., Lim, S., & Poh, C. L. (2017) · ACS Synthetic Biology · doi:10.1021/acssynbio.7b00058 · Cited by 76 · cited 1×
“To further reduce the off-target effects of the treatment, the release of antimicrobials can be engineered to be induced on sensing of external stimuli produced by the target pathogen 202,203 .”
Background
Bacterial interspecies interactions modulate pH-mediated antibiotic tolerance
Aranda-Díaz, A., Obadia, B., Dodge, R., Thomsen, T., Hallberg, Z. F., Güvener, Z. T., Ludington, W. B., & Huang, K. C. (2020) · eLife · doi:10.7554/elife.51493 · Cited by 76 · cited 1×
“In vitro studies of interactions between two gut commensals during antibiotic treatment indicate that symbiotic relationships can have multiple outcomes in effecting differences in antibiotic tolerance in one 99 or both members of the community 100,101 .”
Background
The gut microbiome of healthy long-living people
Deng, F., Li, Y., & Zhao, J. (2019) · Aging · doi:10.18632/aging.101771 · Cited by 75 · cited 1×
“The gastrointestinal tract requires a high, diverse microbial load to carry out requisite microbiome functions 163 .”
Background
Ceftriaxone and Cefotaxime Have Similar Effects on the Intestinal Microbiota in Human Volunteers Treated by Standard-Dose Regimens
Burdet, C., Grall, N., Linard, M., Bridier‐Nahmias, A., Benhayoun, M., Bourabha, K., Magnan, M., Clermont, O., d’Humières, C., Tenaillon, O., et al. (2019) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.02244-18 · Cited by 74
Cotrimoxazole Prophylaxis Increases Resistance Gene Prevalence and α-Diversity but Decreases β-Diversity in the Gut Microbiome of Human Immunodeficiency Virus–Exposed, Uninfected Infants
D’Souza, A. W., Moodley-Govender, E., Berla, B. M., Kelkar, T., Wang, B., Sun, X., Daniels, B. B., Coutsoudis, A., Trehan, I., & Dantas, G. A. (2019) · Clinical Infectious Diseases · doi:10.1093/cid/ciz1186 · Cited by 74
Self-citation
Host adaptation in gut Firmicutes is associated with sporulation loss and altered transmission cycle
Browne, H. P., Almeida, A., Kumar, N., Vervier, K., Adoum, A., Viciani, E., Dawson, N. J. R., Forster, S. C., Cormie, C., Goulding, D., et al. (2021) · Genome biology · doi:10.1186/s13059-021-02428-6 · Cited by 73 · cited 1×
“Members of the Clostridium and Peptostreptococcus genera (along with several other species in the phylum Firmicutes) have the capacity to form endospores, which are non-replicating forms of the cell that are intrinsically resistant to antibiotics, heat and oxygen 78–80 .”
Background
Harnessing CRISPR-Cas systems for precision engineering of designer probiotic lactobacilli
Goh, Y. J., & Barrangou, R. (2018) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2018.11.009 · Cited by 72
Engineer probiotic bifidobacteria for food and biomedical applications - Current status and future prospective
Zuo, F., Chen, S., & Marcotte, H. (2020) · Biotechnology Advances · doi:10.1016/j.biotechadv.2020.107654 · Cited by 72 · cited 1×
“Recent expansions of the toolsets aimed at genetic modification of bacterial and yeast probiotics 197–199 have enabled the engineering of probiotic organisms with more potent and/or targeted anti-pathogenic activities.”
Background
High-throughput fitness screening and transcriptomics identify a role for a type IV secretion system in the pathogenesis of Crohn’s disease-associated Escherichia coli
Elhenawy, W., Hordienko, S., Gould, S., Oberc, A. M., Tsai, C. N., Hubbard, T. P., Waldor, M. K., & Coombes, B. K. (2021) · Nature Communications · doi:10.1038/s41467-021-22306-w · Cited by 72
Targeted adsorption of molecules in the colon with the novel adsorbent‐based Medicinal Product, DAV132: A proof of concept study in healthy subjects
de Gunzburg, J., Ducher, A., Modeß, C., Wegner, D., Oswald, S., Dressman, J., Augustin, V., Féger, C., Andremont, A., Weitschies, W., et al. (2014) · The Journal of Clinical Pharmacology · doi:10.1002/jcph.359 · Cited by 71
Antibiotic Selection Pressure Determination through Sequence-Based Metagenomics
Willmann, M., El-Hadidi, M. S., Huson, D. H., Schütz, M., Weidenmaier, C., Autenrieth, I. B., & Peter, S. (2015) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01504-15 · Cited by 70
Antibiotic Exposure Has Sex-Dependent Effects on the Gut Microbiota and Metabolism of Short-Chain Fatty Acids and Amino Acids in Mice
Gao, H., Shu, Q., Chen, J., Fan, K., Xu, P., Zhou, Q., Li, C., & Zheng, H. X. (2019) · mSystems · doi:10.1128/msystems.00048-19 · Cited by 69 · cited 2×
“…mouse models have reproduced the superior capacity of vancomycin to decrease alpha diversity or increase pathogen susceptibility compared to more than five other antibiotic agents or combinations (including ampicillin, azithromycin, ciprofloxacin and ciprofloxacin– metronidazole) 46,56,57 .”
Background
Gut resistomes, microbiota and antibiotic residues in Chinese patients undergoing antibiotic administration and healthy individuals
Duan, Y., Chen, Z., Tan, L., Wang, X., Xue, Y., Wang, S., Wang, Q., Das, R., Lin, H., Hou, J., et al. (2019) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2019.135674 · Cited by 69 · cited 1×
“Despite increasing the total resistome burden, antibiotics can concurrently lead to a substantial loss of specific ARGs 119 and reduced resistome diversity 116 , which is probably due to taxonomic loss.”
Background
Gut Microbiota Dysbiosis Is Associated with Altered Bile Acid Metabolism in Infantile Cholestasis
Wang, Y., Gao, X., Zhang, X., Xiao, Y., Huang, J., Yu, D., Li, X., Hu, H., Ge, T., Li, D., et al. (2019) · mSystems · doi:10.1128/msystems.00463-19 · Cited by 64
Cross-feeding modulates the rate and mechanism of antibiotic resistance evolution in a model microbial community of Escherichia coli and Salmonella enterica
Adamowicz, E. M., Muza, M., Chacón, J. M., & Harcombe, W. R. (2020) · PLoS Pathogens · doi:10.1371/journal.ppat.1008700 · Cited by 63 · cited 1×
“In vitro studies of interactions between two gut commensals during antibiotic treatment indicate that symbiotic relationships can have multiple outcomes in effecting differences in antibiotic tolerance in one 99 or both members of the community 100,101 .”
Background
Impact of investigational microbiota therapeutic RBX2660 on the gut microbiome and resistome revealed by a placebo-controlled clinical trial
Kwak, S., Choi, J., Hink, T., Reske, K. A., Blount, K., Jones, C. R., Bost, M. H., Sun, X., Burnham, C. D., Dubberke, E. R., et al. (2020) · Microbiome · doi:10.1186/s40168-020-00907-9 · Cited by 62 · cited 2×
“Nonetheless, there are noteworthy therapeutic risks, including the unintended introduction of pathogens and ARGs into the gut of the recipient 185,192 .”
BackgroundSelf-citation
Evolution of the murine gut resistome following broad-spectrum antibiotic treatment
de Nies, L., Busi, S. B., Tsenkova, M., Halder, R., Letellier, E., & Wilmes, P. (2022) · Nature Communications · doi:10.1038/s41467-022-29919-9 · Cited by 59
Factors That Affect Transfer of the IncI1 β-Lactam Resistance Plasmid pESBL-283 between E. coli Strains
Händel, N., Otte, S., Jonker, M. J., Brul, S., & ter Kuile, B. H. (2015) · PLoS ONE · doi:10.1371/journal.pone.0123039 · Cited by 58 · cited 1×
“However, the effects of antibiotics on the rates of HGT (particularly conjugation) are contested, with other studies demonstrating highest plasmid transfer rates in the absence of antibiotics 158–161 .”
Result
Effect of Commonly Used Pediatric Antibiotics on Gut Microbial Diversity in Preschool Children in Burkina Faso: A Randomized Clinical Trial
Oldenburg, C. E., Sié, A., Coulibaly, B., Ouèrmi, L., Dah, C., Tapsoba, C., Bärnighausen, T., Ray, K. J., Zhong, L., Cummings, M. E., et al. (2018) · Open Forum Infectious Diseases · doi:10.1093/ofid/ofy289 · Cited by 57 · cited 1×
“In a comparative study, azithromycin leads to a greater decrease in Simpson’s alpha diversity (less than twofold) 5 days post-treatment than amoxicillin or cotrimoxazole 67 .”
Background
Soluble plantain fibre blocks adhesion and M-cell translocation of intestinal pathogens
Roberts, C. L., Keita, Å. V., Parsons, B. N., Prorok-Hamon, M., Knight, P., Winstanley, C., O’Kennedy, N., Söderholm, J. D., Rhodes, J. M., & Campbell, B. J. (2012) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2012.02.013 · Cited by 55 · cited 1×
“In addition to restructuring the microbiome, it is also possible that several soluble non-starch polysaccharides could serve as a physical barrier against pathogen adherence to the epithelial barrier 181,182 .”
Background
Human Papillomavirus (HPV) Vaccine Effectiveness and Potential Herd Immunity for Reducing Oncogenic Oropharyngeal HPV-16 Prevalence in the United Kingdom: A Cross-sectional Study
Mehanna, H. M., Bryant, T. S., Babrah, J., Louie, K. S., Bryant, J., Spruce, R. J., Batis, N., Olaleye, O., Jones, J. E., Struijk, L., et al. (2018) · Clinical Infectious Diseases · doi:10.1093/cid/ciy1081 · Cited by 55
Microbiome-mediated fructose depletion restricts murine gut colonization by vancomycin-resistant Enterococcus
Isaac, S., Flor‐Duro, A., Carruana, G., Puchades‐Carrasco, L., Quirant, A., López‐Nogueroles, M., Pineda‐Lucena, A., Garcia‐Garcerà, M., & Úbeda, C. (2022) · Nature Communications · doi:10.1038/s41467-022-35380-5 · Cited by 54 · cited 3×
“…mouse models have reproduced the superior capacity of vancomycin to decrease alpha diversity or increase pathogen susceptibility compared to more than five other antibiotic agents or combinations (including ampicillin, azithromycin, ciprofloxacin and ciprofloxacin– metronidazole) 46,56,57 .”
Background
Impact of Oral Fidaxomicin Administration on the Intestinal Microbiota and Susceptibility to Clostridium difficile Colonization in Mice
Ajami, N. J., Cope, J. L., Wong, M. C., Petrosino, J. F., & Chesnel, L. (2018) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.02112-17 · Cited by 53 · cited 2×
“Given that antibiotics vary in their spectrum of activity against the diverse members of the commensal gut microbiome, the choice of treatments with a narrower spectrum could result in less perturbation to the microbiome and faster community recovery 169 .”
Background
Humans are animals, but are animals human enough? A systematic review and meta-analysis on interspecies differences in renal drug clearance
Jansen, K., Casellas, C. P., Groenink, L., Wever, K. E., & Masereeuw, R. (2020) · Drug Discovery Today · doi:10.1016/j.drudis.2020.01.018 · Cited by 53
Strain-resolved microbiome sequencing reveals mobile elements that drive bacterial competition on a clinical timescale
Bishara, A., Moss, E. L., Tkachenko, E., Kang, J. B., Zlitni, S., Culver, R. N., Andermann, T. M., Weng, Z., Wood-Bouwens, C. M., Handy, C., et al. (2020) · Genome Medicine · doi:10.1186/s13073-020-00747-0 · Cited by 53 · cited 1×
“…stool short-read shotgun metagenomics or 16S rRNA amplicon sequencing as the main techniques for determining community structure, which generally does not provide strain-level resolution of the microbiome (a requirement for understanding gut microbiome AMR composition, as discussed below) 68,69 .”
Background
Strain-Dependent Inhibition of Clostridioides difficile by Commensal Clostridia Carrying the Bile Acid-Inducible ( bai ) Operon
Reed, A. D., Nethery, M. A., Stewart, A. K., Barrangou, R., & Theriot, C. M. (2020) · Journal of Bacteriology · doi:10.1128/jb.00039-20 · Cited by 49
An open randomized multicentre Phase 2 trial to assess the safety of DAV132 and its efficacy to protect gut microbiota diversity in hospitalized patients treated with fluoroquinolones
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Role of Microbiome in Carcinogenesis Process and Epigenetic Regulation of Colorectal Cancer
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Background
Consumption of a Western-Style Diet Modulates the Response of the Murine Gut Microbiome to Ciprofloxacin
Cabral, D. J., Wurster, J. I., Korry, B. J., Penumutchu, S., & Belenky, P. A. (2020) · mSystems · doi:10.1128/msystems.00317-20 · Cited by 45 · cited 1×
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THE EFFECT OF ANTIBACTERIAL DRUGS ON THE FECAL FLORA OF MICE
Dubos, R. J., Schaedler, R. W., & Stephens, M. (1963) · The Journal of Experimental Medicine · doi:10.1084/jem.117.2.231 · Cited by 44
Early Parenteral Administration of Ceftiofur has Gender-Specific Short- and Long-Term Effects on the Fecal Microbiota and Growth in Pigs from the Suckling to Growing Phase
Ruczizka, U., Metzler-Zebeli, B. U., Unterweger, C., Mann, E., Schwarz, L., Knecht, C., & Hennig‐Pauka, I. (2019) · Animals · doi:10.3390/ani10010017 · Cited by 44
Impact of azithromycin mass drug administration on the antibiotic-resistant gut microbiome in children: a randomized, controlled trial
Pickering, H. C., Hart, J., Burr, S. E., Stabler, R. A., Maleta, K. M., Kalua, K., Bailey, R. L., & Holland, M. J. (2022) · Gut Pathogens · doi:10.1186/s13099-021-00478-6 · Cited by 43 · cited 3×
“Antibiotics expectedly enrich for ARGs that confer resistance to the treatment agent 33,34,51,62–66 ,114,115, 117, 119– 123 through selection of bacterial strains Importantly, the effects of antibiotics on the gut resistome vary substantially depending on the nature of the administered drug…”
Background
The potential utility of fecal (or intestinal) microbiota transplantation in controlling infectious diseases
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SYN-004 (ribaxamase), an oral beta-lactamase, mitigates antibiotic-mediated dysbiosis in a porcine gut microbiome model
Connelly, S., Bristol, J. A., Hubert, S., Subramanian, P., Hasan, N. A., Colwell, R. R., & Kaleko, M. (2017) · Journal of Applied Microbiology · doi:10.1111/jam.13432 · Cited by 42 · cited 3×
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Dietary Xanthan Gum Alters Antibiotic Efficacy against the Murine Gut Microbiota and Attenuates Clostridioides difficile Colonization
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Effects of Antibiotics on the Intestinal Microbiota of Mice
Hertz, F. B., Budding, A. E., van der Lugt-Degen, M., Savelkoul, P. H. M., Løbner‐Olesen, A., & Frimodt‐Møller, N. (2020) · Antibiotics · doi:10.3390/antibiotics9040191 · Cited by 41
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Randomized Controlled Trial of Oral Vancomycin Treatment in Clostridioides difficile-Colonized Patients
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BackgroundSelf-citation
Saccharomyces boulardii CNCM I-745 Modulates the Fecal Bile Acids Metabolism During Antimicrobial Therapy in Healthy Volunteers
Kelly, C. P., Chong-Nguyen, C., Palmieri, L., Pallav, K., Dowd, S. E., Humbert, L., Seksik, P., Bado, A., Coffin, B., Rainteau, D. P., et al. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.00336 · Cited by 36
A Solution to Antifolate Resistance in Group B Streptococcus : Untargeted Metabolomics Identifies Human Milk Oligosaccharide-Induced Perturbations That Result in Potentiation of Trimethoprim
Chambers, S. A., Moore, R. E., Craft, K. M., Thomas, H. C., Das, R. K., Manning, S. D., Codreanu, S. G., Sherrod, S. D., Aronoff, D. M., MCLEAN, J. A. J., et al. (2020) · mBio · doi:10.1128/mbio.00076-20 · Cited by 36 · cited 1×
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Background
Antibiotic-driven intestinal dysbiosis in pediatric short bowel syndrome is associated with persistently altered microbiome functions and gut-derived bloodstream infections
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Authors: Fishbein, S. R. S., Mahmud, B., & Dantas, G.
Affiliations: Washington University in St. Louis (US)
Corresponding author: Dantas, Gautam
ORCID: Fishbein, Skye R. S.
Mahmud, Bejan
Dantas, Gautam
Venue: Nature Reviews Microbiology
Publisher: Springer Science and Business Media LLC
Published: 2023-07-25
Volume: 21
Issue: 12
Pages: 772-788
ISSN: 1740-1526 (ISSN-L)
1740-1534
DOI: 10.1038/s41579-023-00933-y
PMC: PMC12087466
OpenAlex: W4385240643
Cited by: 440
References: 229
Citations by year: 2026: 152 · 2025: 165 · 2024: 115 · 2023: 7
FWCI: 11.59
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Nature Reviews Microbiology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: U.S. Department of Health and Human Services
National Institutes of Health
Centers for Disease Control and Prevention (R01OH011578)
Agency for Healthcare Research and Quality (R01 HS027621)
National Institute of Allergy and Infectious Diseases (U01AI123394, R01AI155893)
National Institute of Diabetes and Digestive and Kidney Diseases (T32DK077653)
National Institute for Occupational Safety and Health (R01 OH011578)
National Center for Complementary and Integrative Health (R01AT009741)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD092414)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
Physical Sciences › Environmental Science › Ecology › Microbial Community Ecology and Physiology
Keywords: gut microbiota, antibiotics, microbiome perturbation, microbiome recovery, gastrointestinal diseases, autoimmune disease, multi-omics profiling
MeSH terms: Gastrointestinal Microbiome, Anti-Bacterial Agents, Gastrointestinal Tract, Microbiota

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