Microbial diversity in individuals and their household contacts following typical antibiotic courses
Shira R Abeles, Marcus B Jones, Tasha M Santiago-Rodriguez, Melissa Ly, Niels Klitgord, Shibu Yooseph, Karen E Nelson, David T Pride, Shira R Abeles, Marcus B Jones, Tasha M Santiago-Rodriguez, Melissa Ly, Niels Klitgord, Shibu Yooseph, Karen E Nelson, David T Pride
Abstract
Background: Antibiotics are a mainstay of treatment for bacterial infections worldwide, yet the effects of typical antibiotic prescriptions on human indigenous microbiota have not been thoroughly evaluated. We examined the effects of the two most commonly prescribed antibiotics (amoxicillin and azithromycin) in the USA to discern whether short-term antibiotic courses may have prolonged effects on human microbiota.
Results: We sampled the feces, saliva, and skin specimens from a cohort of unrelated, cohabitating individuals over 6 months. An individual in each household was given an antibiotic, and the other a placebo to discern antibiotic impacts on microbiota, as well as determine whether antibiotic use might reshape the microbiota of each household. We observed household-specific patterns of microbiota on each body surface, which persevered despite antibiotic perturbations. While the gut microbiota within an individual became more dissimilar over time, there was no evidence that the use of antibiotics accelerated this process when compared to household members. There was a significant change in microbiota diversity in the gut and mouth in response to antibiotics, but analogous patterns were not observed on the skin. Those who received 7 days of amoxicillin generally had greater reductions in diversity compared to those who received 3 days, in contrast to those who received azithromycin.
Conclusions: As few as 3 days of treatment with the most commonly prescribed antibiotics can result in sustained reductions in microbiota diversity, which could have implications for the maintenance of human health and resilience to disease.
Keywords: 16S rRNA; Antibiotic courses; Antibiotic perturbations; Antibiotics; Gut; Microbiome; Saliva; Skin.
Figures
![Fig. 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4967329/bin/40168_2016_187_Fig1_HTML.jpg)
![Fig. 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4967329/bin/40168_2016_187_Fig2_HTML.jpg)
![Fig. 3](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4967329/bin/40168_2016_187_Fig3_HTML.jpg)
![Fig. 4](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4967329/bin/40168_2016_187_Fig4_HTML.jpg)
![Fig. 5](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4967329/bin/40168_2016_187_Fig5_HTML.jpg)
![Fig. 6](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4967329/bin/40168_2016_187_Fig6_HTML.jpg)
![Fig. 7](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4967329/bin/40168_2016_187_Fig7_HTML.jpg)
![Fig. 8](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4967329/bin/40168_2016_187_Fig8_HTML.jpg)
References
- Costello EK, Lauber CL, Hamady M, Fierer N, Gordon JI, Knight R. Bacterial community variation in human body habitats across space and time. Science. 2009;326:1694–1697. doi: 10.1126/science.1177486.
- Minot S, Sinha R, Chen J, Li H, Keilbaugh SA, Wu GD, Lewis JD, Bushman FD. The human gut virome: inter-individual variation and dynamic response to diet. Genome Res. 2011;21:1616–1625. doi: 10.1101/gr.122705.111.
- Pride DT, Salzman J, Haynes M, Rohwer F, Davis-Long C, White RA, 3rd, Loomer P, Armitage GC, Relman DA. Evidence of a robust resident bacteriophage population revealed through analysis of the human salivary virome. ISME J. 2012;6:915–926. doi: 10.1038/ismej.2011.169.
- Willner D, Furlan M, Schmieder R, Grasis JA, Pride DT, Relman DA, Angly FE, McDole T, Mariella RP, Jr, Rohwer F, Haynes M. Metagenomic detection of phage-encoded platelet-binding factors in the human oral cavity. Proc Natl Acad Sci U S A. 2011;108(Suppl 1):4547–4553. doi: 10.1073/pnas.1000089107.
- Breitbart M, Hewson I, Felts B, Mahaffy JM, Nulton J, Salamon P, Rohwer F. Metagenomic analyses of an uncultured viral community from human feces. J Bacteriol. 2003;185:6220–6223. doi: 10.1128/JB.185.20.6220-6223.2003.
- Reyes A, Haynes M, Hanson N, Angly FE, Heath AC, Rohwer F, Gordon JI. Viruses in the faecal microbiota of monozygotic twins and their mothers. Nature. 2010;466:334–338. doi: 10.1038/nature09199.
- Willing BP, Dicksved J, Halfvarson J, Andersson AF, Lucio M, Zheng Z, Jarnerot G, Tysk C, Jansson JK, Engstrand L. A pyrosequencing study in twins shows that gastrointestinal microbial profiles vary with inflammatory bowel disease phenotypes. Gastroenterology. 2010;139:1844–1854. doi: 10.1053/j.gastro.2010.08.049.
- Arrieta MC, Stiemsma LT, Dimitriu PA, Thorson L, Russell S, Yurist-Doutsch S, Kuzeljevic B, Gold MJ, Britton HM, Lefebvre DL, et al. Early infancy microbial and metabolic alterations affect risk of childhood asthma. Sci Transl Med. 2015;7:307ra152. doi: 10.1126/scitranslmed.aab2271.
- Relman DA. The human microbiome: ecosystem resilience and health. Nutr Rev. 2012;70(Suppl 1):S2–9. doi: 10.1111/j.1753-4887.2012.00489.x.
- Fujimura KE, Slusher NA, Cabana MD, Lynch SV. Role of the gut microbiota in defining human health. Expert Rev Anti Infect Ther. 2010;8:435–454. doi: 10.1586/eri.10.14.
- Ley RE, Backhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI. Obesity alters gut microbial ecology. Proc Natl Acad Sci U S A. 2005;102:11070–11075. doi: 10.1073/pnas.0504978102.
- Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature. 2006;444:1022–1023. doi: 10.1038/4441022a.
- Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444:1027–1031. doi: 10.1038/nature05414.
- Qin J, Li Y, Cai Z, Li S, Zhu J, Zhang F, Liang S, Zhang W, Guan Y, Shen D, et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature. 2012;490:55–60. doi: 10.1038/nature11450.
- Craven M, Egan CE, Dowd SE, McDonough SP, Dogan B, Denkers EY, Bowman D, Scherl EJ, Simpson KW. Inflammation drives dysbiosis and bacterial invasion in murine models of ileal Crohn’s disease. PLoS One. 2012;7:e41594. doi: 10.1371/journal.pone.0041594.
- Hsiao EY, McBride SW, Hsien S, Sharon G, Hyde ER, McCue T, Codelli JA, Chow J, Reisman SE, Petrosino JF, et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell. 2013;155:1451–1463. doi: 10.1016/j.cell.2013.11.024.
- Lay C, Rigottier-Gois L, Holmstrom K, Rajilic M, Vaughan EE, de Vos WM, Collins MD, Thiel R, Namsolleck P, Blaut M, Dore J. Colonic microbiota signatures across five northern European countries. Appl Environ Microbiol. 2005;71:4153–4155. doi: 10.1128/AEM.71.7.4153-4155.2005.
- Markle JG, Frank DN, Mortin-Toth S, Robertson CE, Feazel LM, Rolle-Kampczyk U, von Bergen M, McCoy KD, Macpherson AJ, Danska JS. Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity. Science. 2013;339:1084–1088. doi: 10.1126/science.1233521.
- Mueller S, Saunier K, Hanisch C, Norin E, Alm L, Midtvedt T, Cresci A, Silvi S, Orpianesi C, Verdenelli MC, et al. Differences in fecal microbiota in different European study populations in relation to age, gender, and country: a cross-sectional study. Appl Environ Microbiol. 2006;72:1027–1033. doi: 10.1128/AEM.72.2.1027-1033.2006.
- Slots J, Feik D, Rams TE. Age and sex relationships of superinfecting microorganisms in periodontitis patients. Oral Microbiol Immunol. 1990;5:305–308. doi: 10.1111/j.1399-302X.1990.tb00430.x.
- Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, Contreras M, Magris M, Hidalgo G, Baldassano RN, Anokhin AP, et al. Human gut microbiome viewed across age and geography. Nature. 2012;486:222–227.
- Zapata HJ, Quagliarello VJ. The microbiota and microbiome in aging: potential implications in health and age-related diseases. J Am Geriatr Soc. 2015;63:776–781. doi: 10.1111/jgs.13310.
- Fleming-Dutra KE, Hersh AL, Shapiro DJ, Bartoces M, Enns EA, File TM, Jr, Finkelstein JA, Gerber JS, Hyun DY, Linder JA, et al. Prevalence of inappropriate antibiotic prescriptions among US ambulatory care visits, 2010-2011. JAMA. 2016;315:1864–1873. doi: 10.1001/jama.2016.4151.
- Dethlefsen L, Huse S, Sogin ML, Relman DA. The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing. PLoS Biol. 2008;6:e280. doi: 10.1371/journal.pbio.0060280.
- Zaura E, Brandt BW, Teixeira de Mattos MJ, Buijs MJ, Caspers MP, Rashid MU, Weintraub A, Nord CE, Savell A, Hu Y, et al. Same exposure but two radically different responses to antibiotics: resilience of the salivary microbiome versus long-term microbial shifts in feces. MBio 2015;e01693-15.
- Chang JY, Antonopoulos DA, Kalra A, Tonelli A, Khalife WT, Schmidt TM, Young VB. Decreased diversity of the fecal microbiome in recurrent Clostridium difficile-associated diarrhea. J Infect Dis. 2008;197:435–438. doi: 10.1086/525047.
- Schubert AM, Sinani H, Schloss PD. Antibiotic-induced alterations of the murine gut microbiota and subsequent effects on colonization resistance against Clostridium difficile. MBio. 2015;6:e00974. doi: 10.1128/mBio.00974-15.
- Song SJ, Lauber C, Costello EK, Lozupone CA, Humphrey G, Berg-Lyons D, Caporaso JG, Knights D, Clemente JC, Nakielny S, et al. Cohabiting family members share microbiota with one another and with their dogs. Elife. 2013;2:e00458.
- Lax S, Smith DP, Hampton-Marcell J, Owens SM, Handley KM, Scott NM, Gibbons SM, Larsen P, Shogan BD, Weiss S, et al. Longitudinal analysis of microbial interaction between humans and the indoor environment. Science. 2014;345:1048–1052. doi: 10.1126/science.1254529.
- Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, Sogin ML, Jones WJ, Roe BA, Affourtit JP, et al. A core gut microbiome in obese and lean twins. Nature. 2009;457:480–484. doi: 10.1038/nature07540.
- Moore AM, Ahmadi S, Patel S, Gibson MK, Wang B, Ndao MI, Deych E, Shannon W, Tarr PI, Warner BB, Dantas G. Gut resistome development in healthy twin pairs in the first year of life. Microbiome. 2015;3:27. doi: 10.1186/s40168-015-0090-9.
- Penders J, Stobberingh EE, Savelkoul PH, Wolffs PF. The human microbiome as a reservoir of antimicrobial resistance. Front Microbiol. 2013;4:87. doi: 10.3389/fmicb.2013.00087.
- Lozupone C, Hamady M, Knight R. UniFrac—an online tool for comparing microbial community diversity in a phylogenetic context. BMC Bioinformatics. 2006;7:371. doi: 10.1186/1471-2105-7-371.
- Kort R, Caspers M, van de Graaf A, van Egmond W, Keijser B, Roeselers G. Shaping the oral microbiota through intimate kissing. Microbiome. 2014;2:41. doi: 10.1186/2049-2618-2-41.
- Faith JJ, Guruge JL, Charbonneau M, Subramanian S, Seedorf H, Goodman AL, Clemente JC, Knight R, Heath AC, Leibel RL, et al. The long-term stability of the human gut microbiota. Science. 2013;341:1237439. doi: 10.1126/science.1237439.
- Grice EA, Kong HH, Renaud G, Young AC, Bouffard GG, Blakesley RW, Wolfsberg TG, Turner ML, Segre JA. A diversity profile of the human skin microbiota. Genome Res. 2008;18:1043–1050. doi: 10.1101/gr.075549.107.
- Gao Z, Tseng CH, Pei Z, Blaser MJ. Molecular analysis of human forearm superficial skin bacterial biota. Proc Natl Acad Sci U S A. 2007;104:2927–2932. doi: 10.1073/pnas.0607077104.
- Hanski I, von Hertzen L, Fyhrquist N, Koskinen K, Torppa K, Laatikainen T, Karisola P, Auvinen P, Paulin L, Makela MJ, et al. Environmental biodiversity, human microbiota, and allergy are interrelated. Proc Natl Acad Sci U S A. 2012;109:8334–8339. doi: 10.1073/pnas.1205624109.
- Whiteley AS, Jenkins S, Waite I, Kresoje N, Payne H, Mullan B, Allcock R, O'Donnell A. Microbial 16S rRNA Ion Tag and community metagenome sequencing using the Ion Torrent (PGM) Platform. J Microbiol Methods. 2012;91:80–88. doi: 10.1016/j.mimet.2012.07.008.
- Rothberg JM, Hinz W, Rearick TM, Schultz J, Mileski W, Davey M, Leamon JH, Johnson K, Milgrew MJ, Edwards M, et al. An integrated semiconductor device enabling non-optical genome sequencing. Nature. 2011;475:348–352. doi: 10.1038/nature10242.
- Ewing B, Green P. Base-calling of automated sequencer traces using phred. II. Error probabilities. Genome Res. 1998;8:186–194. doi: 10.1101/gr.8.3.186.
- Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD, Costello EK, Fierer N, Pena AG, Goodrich JK, Gordon JI, et al. QIIME allows analysis of high-throughput community sequencing data. Nat Methods. 2010;7:335–336. doi: 10.1038/nmeth.f.303.
- DeSantis TZ, Hugenholtz P, Larsen N, Rojas M, Brodie EL, Keller K, Huber T, Dalevi D, Hu P, Andersen GL. Greengenes, a chimera-checked 16S rRNA gene database and workbench compatible with ARB. Appl Environ Microbiol. 2006;72:5069–5072. doi: 10.1128/AEM.03006-05.
- Gotelli NJ, Colwell RK. Quantifying biodiversity: procedures and pitfalls in the measurement and comparison of species richness. Ecol Lett. 2001;4:379–391. doi: 10.1046/j.1461-0248.2001.00230.x.
- Saeed AI, Sharov V, White J, Li J, Liang W, Bhagabati N, Braisted J, Klapa M, Currier T, Thiagarajan M, et al. TM4: a free, open-source system for microarray data management and analysis. Biotechniques. 2003;34:374–378.
- Breitling R, Armengaud P, Amtmann A, Herzyk P. Rank products: a simple, yet powerful, new method to detect differentially regulated genes in replicated microarray experiments. FEBS Lett. 2004;573:83–92. doi: 10.1016/j.febslet.2004.07.055.
Source: PubMed