Abstract
Antibiotics are commonly used to treat infectious diseases; however, persistence is often expressed by the pathogenic bacteria and their long-term relative effect on the host have been neglected. The present study investigated the impact of antibiotics in gut microbiota (GM) and metabolism of host. The effect of ampicillin antibiotics on GM of Drosophila melanogaster was analyzed through deep sequencing of 16S rRNA amplicon gene. The dominant phyla consisted of Proteobacteria, Bacteroidetes, Firmicutes, Actinobacteria, Planctomycetes, Chloroflexi, Euryarchaeota, Acedobacteria, Verrucomicrobia, and Cyanobacteria. It was found that the composition of GM was significantly altered on administration of antibiotics. On antibiotic treatments, there were decline in relative abundance of Proteobacteria and Firmicutes, while there were increase in relative abundance of Chlorophyta and Bacteroidota. High abundance of 14 genera, viz., Wolbachia, Lactobacillus, Bacillus, Pseudomonas, Thiolamprovum, Pseudoalteromonas, Vibrio, Romboutsia, Staphylococcus, Alteromonas, Clostridium, Lysinibacillus, Litoricola, and Cellulophaga were significant (p ≤ 0.05) upon antibiotic treatment. Particularly, the abundance of Acetobacter was significantly (p ≤ 0.05) declined but increased for Wolbachia. Further, a significant (p ≤ 0.05) increase in Wolbachia endosymbiont of D. melanogaster, Wolbachia endosymbiont of Curculio okumai, and Wolbachia pipientis and a decrease in the Acinetobacter sp. were observed. We observed an increase in functional capacity for biosynthesis of certain nucleotides and the enzyme activities. Further, the decrease in antimicrobial peptide production in the treated group and potential effects on the host’s defense mechanisms were observed. This study helps shed light on an often-overlooked dimension, namely the persistence of antibiotics’ effects on the host.
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Data availability
The data supporting the conclusions of this study can be accessed through the NIH Sequence Read Archive under submission ID SUB148280, associated with BioProject ID PRJNA1078087, titled “Drosophila melanogaster Gut Microbiomes.”
References
Aloisio I, Mazzola G, Corvaglia LT, Tonti G, Faldella G, Biavati B, Di Gioia D (2014) Influence of intrapartum antibiotic prophylaxis against group B Streptococcus on the early newborn gut composition and evaluation of the anti-Streptococcus activity of Bifidobacterium strains. Appl Microbiol Biotechnol 98:6051–6060
Antonioli L, Blandizzi C, Pacher P, Haskó G (2013) Immunity, inflammation and cancer: a leading role for adenosine. Nat Rev Cancer 13(12):842–857
Argue KJ, Yun AJ, Neckameyer WS (2013) Early manipulation of juvenile hormone has sexually dimorphic effects on mature adult behavior in Drosophila melanogaster. Horm Behav 64(4):589–597
Arnold KE, Boxall AB, Brown AR, Cuthbert RJ, Gaw S, Hutchinson TH, Jobling S, Madden JC, Metcalfe CD, Naidoo V, Shore RF (2013) Assessing the exposure risk and impacts of pharmaceuticals in the environment on individuals and ecosystems. Biol lett 9(4):20130493
Azad MB, Konya T, Persaud RR, Guttman DS, Chari RS, Field CJ, Sears MR, Mandhane PJ, Turvey SE, Subbarao P, Becker AB (2016) CHILD Study Investigators Impact of maternal intrapartum antibiotics, method of birth and breastfeeding on gut microbiota during the first year of life: a prospective cohort study. BJOG 123(6):983–993
Blaser M (2011) Stop the killing of beneficial bacteria. Nature 476(7361):393–394. https://doi.org/10.1038/476393a
Broderick NA, Lemaitre B (2012) Gut-associated microbes of Drosophila melanogaster. Gut Microbes 3:307–321. https://doi.org/10.4161/gmic.19896
Broderick NA, Raffa KF, Handelsman J (2006) Midgut bacteria required for Bacillus thuringiensis insecticidal activity. Proc Natl Acad Sci 103(41):15196–15199
Brune A (1998) Termite guts: the world’s smallest bioreactors. Trends Biotechnol 16(1):16–21
Buchon N, Broderick NA, Chakrabarti S, Lemaitre B (2009) Invasive and indigenous microbiota impact intestinal stem cell activity through multiple pathways in Drosophila. Genes Dev 23(19):2333–2344. https://doi.org/10.1101/gad.1827009
Chatterjee A, Roy D, Patnaik E, Nongthomba U (2016) Muscles provide protection during microbial infection by activating innate immune response pathways in Drosophila and zebrafish. Dis Model Mech 9(6):697–705
Chopra I, Roberts M (2001) Tetracycline antibiotics: mode of action, applications, molecular biology, and epidemiology of bacterial resistance. Microbiol Mol Biol Rev 65(2):232–260
Coker MO, Hoen AG, Dade E, Lundgren S, Li Z, Wong AD, Zens MS, Palys TJ, Morrison HG, Sogin ML, Baker ER (2020) Specific class of intrapartum antibiotics relates to maturation of the infant gut microbiota: a prospective cohort study. BJOG: An Int J Obstetrics & Gynaecology 127(2):217–227
Dethlefsen L, Relman DA (2011) Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proc Natl Acad Sci USA 108(supplement_1) 4554–4561
Dowd SE, Sun Y, Wolcott RD, Domingo A, Carroll JA (2008) Bacterial tag–encoded FLX amplicon pyrosequencing (bTEFAP) for microbiome studies: bacterial diversity in the ileum of newly weaned Salmonella-infected pigs. Foodborne Pathog Dis 5(4):459–472
Dubourg G, Lagier JC, Robert C, Armougom F, Hugon P, Metidji S, Dione N, Dangui NPM, Pfleiderer A, Abrahao J, Musso D, Papazian L, Brouqui P, Bibi F, Yasir M, Vialettes B, Raoult D (2014) Culturomics and pyrosequencing evidence of the reduction in gut microbiota diversity in patients with broad-spectrum antibiotics. Int J Antimicrob Agents 44(2):117–124. https://doi.org/10.1016/j.ijantimicag.2014.04.020
Elya C, Zhang V, Ludington WB, Eisen MB (2016) Stable host gene expression in the gut of adult Drosophila melanogaster with different bacterial mono-associations. PLoS ONE 11(11):e0167357
Eren AM, Zozaya M, Taylor CM, Dowd SE, Martin DH, Ferris MJ (2011) Exploring the diversity of Gardnerella vaginalis in the genitourinary tract microbiota of monogamous couples through subtle nucleotide variation. PLoS ONE 6(10):e26732
Gruntenko NE, Rauschenbach IY (2008) Interplay of JH, 20E and biogenic amines under normal and stress conditions and its effect on reproduction. J Insect Physiol 54(6):902–908
Ha EM, Oh CT, Bae YS, Lee WJ (2005) A direct role for dual oxidase in Drosophila gut immunity. Science 310(5749):847–850
Hanna ME, Bednářová A, Rakshit K, Chaudhuri A, O’Donnell JM, Krishnan N (2015) Perturbations in dopamine synthesis lead to discrete physiological effects and impact oxidative stress response in Drosophila. J Insect Physiol 73:11–19
Heinsen FA, Knecht H, Neulinger SC, Schmitz RA, Knecht C, Kühbacher T, Rosenstiel PC, Schreiber S, Friedrichs AK, Ott SJ (2015) Dynamic changes of the luminal and mucosa-associated gut microbiota during and after antibiotic therapy with paromomycin. Gut Microbes 6(4):243–254
Hoffmann AA, Turelli M, Harshman LG (1990) Factors affecting the distribution of cytoplasmic incompatibility in Drosophila simulans. Genetics 126(4):933–948
Hosokawa T, Kikuchi Y, Nikoh N, Shimada M, Fukatsu T (2006) Strict host-symbiont cospeciation and reductive genome evolution in insect gut bacteria. PLoS Biol 4(10):e337
Janson EM III, Stireman JO, Singer MS, Abbot P (2008) Phytophagous insect–microbe mutualisms and adaptive evolutionary diversification. Evolution 62(5):997–1012
Jimmerson LC, Bushman LR, Ray ML, Anderson PL, Kiser JJ (2017) A LC-MS/MS method for quantifying adenosine, guanosine and inosine nucleotides in human cells. Pharm Res 34:73–83
Kato K, Ishiwa A (2015) The role of carbohydrates in infection strategies of enteric pathogens. Trop Med Health 43(1):41–52
Kaufman MG, Klug MJ (1991) The contribution of hindgut bacteria to dietary carbohydrate utilization by crickets (Orthoptera, Gryllidae). Comp Biochem Physiol A-Physiol 98:117–123
Khan I, Azhar EI, Abbas AT, Kumosani T, Barbour EK, Raoult D, Yasir M (2016) Metagenomic analysis of antibiotic-induced changes in gut microbiota in a pregnant rat model. Front Pharmacol 7:104
Leonard MM, Valitutti F, Karathia H, Pujolassos M, Kenyon V, Fanelli B, Troisi J, Subramanian P, Camhi S, Colucci A, Serena G (2021) Microbiome signatures of progression toward celiac disease onset in at-risk children in a longitudinal prospective cohort study. Proc Natl Acad Sci 118(29):e2020322118
Levy M, Kolodziejczyk AA, Thaiss CA, Elinav E (2017) Dysbiosis and the immune system. Nat Rev Immunol 17(4):219–232
Li LH, Cowie CH, Gray LG, Moran DM, Clark TD, Rinehart KL Jr (1977) Effects of streptovaricins and their degradation products on RNA-directed DNA polymerase of Rauscher leukemia virus. J Natl Cancer Inst 58(2):239–243
Mars RA, Yang Y, Ward T, Houtti M, Priya S, Lekatz HR, Tang X, Sun Z, Kalari KR, Korem T, Bhattarai Y (2020) Longitudinal multi-omics reveals subset-specific mechanisms underlying irritable bowel syndrome. Cell 182(6):1460–1473
Martino ME, Ma D, Leulier F (2017) Microbial influence on Drosophila biology. Curr Opin Microbiol 38:165–170. https://doi.org/10.1016/j.mib.2017.06.004
Milani C, Duranti S, Bottacini F, Casey E, Turroni F, Mahony J, Belzer C, Palacio SD, Montes SA, Mancabelli L, Lugli GA, Rodriguez JM, Bode L, de Vos W, Gueimonde M, Margolles A, van Sinderen D, Ventura M (2017) The first microbial colonizers of the human gut: composition, activities, and health implications of the infant gut microbiota. Microbiol Mol Biol Rev 81(4):1–67
Raymann K, Shaffer Z, Moran NA (2017) Antibiotic exposure perturbs the gut microbiota and elevates mortality in honeybees. PLoS Biol 15(3):e2001861
Riquelme E, Zhang Y, Zhang L et al (2019) Tumor microbiome diversity and composition influence pancreatic cancer outcomes. Cell 178:795–806
Rousset F, Bouchon D, Pintureau B, Juchault P, Solignac M (1992) Wolbachia endosymbionts responsible for various alterations of sexuality in arthropods. Proc Roy Soc London, Ser B, Biol Sci. 250(1328):91–98
Ryu JH, Ha EM, Oh CT, Seol JH, Brey PT, Jin I, Lee DG, Kim J, Lee D, Lee WJ (2006) An essential complementary role of NF-κB pathway to microbicidal oxidants in Drosophila gut immunity. EMBO J 25(15):3693–3701
Ryu JH, Kim SH, Lee HY, Bai JY, Nam YD, Bae JW, Lee DG, Shin SC, Ha EM, Lee WJ (2008) Innate immune homeostasis by the homeobox gene caudal and commensal-gut mutualism in Drosophila. Science 319:777–782. https://doi.org/10.1126/science.1149357
Schultz-Cherry S, Dybdahl-Sissoko N, Neumann G, Kawaoka Y, Hinshaw VS (2001) Influenza virus ns1 protein induces apoptosis in cultured cells. J Virol 75(17):7875–7881
Serbus LR, Casper-Lindley C, Landmann F, Sullivan W (2008) The genetics and cell biology of Wolbachia-host interactions. Annu Rev Genet 42:683–707
Shibata T, Ohto U, Nomura S, Kibata K, Motoi Y, Zhang Y, Murakami Y, Fukui R, Ishimoto T, Sano S, Ito T (2016) Guanosine and its modified derivatives are endogenous ligands for TLR7. Int Immunol 28(5):211–222
Snook RR, Cleland SY, Wolfner MF, Karr TL (2000) Offsetting effects of Wolbachia infection and heat shock on sperm production in Drosophila simulans: analyses of fecundity, fertility and accessory gland proteins. Genetics 155(1):167–178
Stokholm J, Sevelsted A, Bønnelykke K, Bisgaard H (2014) Maternal propensity for infections and risk of childhood asthma: a registry-based cohort study. Lancet Respir Med 2(8):631–637
Stouthamer R, Breeuwer JAJ, Luck RF, Werren JH (1993) Molecular identification of microorganisms associated with parthenogenesis. Nature 361(6407):66–68
Swanson KS, Dowd SE, Suchodolski JS, Middelbos IS, Vester BM, Barry KA, Nelson KE, Torralba M, Henrissat B, Coutinho PM, Cann IK (2011) Phylogenetic and gene-centric metagenomics of the canine intestinal microbiome reveals similarities with humans and mice. ISME J 5(4):639–649
Tilg H, Cani PD, Mayer EA (2016) Gut Microbiome and Liver Diseases Gut 65:2035–2044
Tilg H, Adolph TE, Gerner RR et al (2018) The intestinal microbiota in colorectal cancer. Cancer Cell 33:954–964
Trebicka J, Macnaughtan J, Schnabl B et al (2021) The microbiota in cirrhosis and its role in hepatic decompensation. J Hepatol 75(Suppl 1):S67-81
Ueno T, Tomita J, Kume S, Kume K (2012) Dopamine modulates metabolic rate and temperature sensitivity in Drosophila melanogaster. PLoS ONE 7(2):e31513
Van Boeckel TP, Brower C, Gilbert M, Grenfell BT, Levin SA, Robinson TP, Teillant A, Laxminarayan R (2015) Global trends in antimicrobial use in food animals. Proc Natl Acad Sci 112(18):5649–5654
Volkova A, Ruggles K, Schulfer A, Gao Z, Ginsberg SD, Blaser MJ (2021) Effects of early-life penicillin exposure on the gut microbiome and frontal cortex and amygdala gene expression. iScience 24(7):102797. https://doi.org/10.1016/j.isci.2021.102797
Werren JH, Baldo L, Clark ME (2008) Wolbachia: master manipulators of invertebrate biology. Nat Rev Microbiol 6(10):741–751
Wong AC-N, Wang Q-P, Morimoto J, Senior AM, Lihoreau M, Neely GG, et al (2017) Gut microbiota modifies olfactory-guided microbial preferences and foraging decisions in Drosophila. Curr Biol 27:2397-2404.e4 https://doi.org/10.1016/j.cub.2017.07.022
Funding
The authors express their gratitude to the Indian Institute of Science (IISc) for offering essential facilities to conduct this research. The first author acknowledges the financial support received through the DBT-RA post-doctoral program in Biotechnology and Life Science, including fellowship and contingency, under Grant ID-DBT-RA/2022/January NE/994.
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Asem Sanjit Singh: Conceptualisation, designed the experiment, carried out the experiments, analyzed the experiment results, and writing original draft. Dhruv Pathak: Carried out the experiment; Upendra Nongthomba: Conceptualisation, designed the experiments, commented on the manuscript; Manaharmayum Shaya Devi: Data analysis, assisted in manuscript preparation; Abass Toba Anifowoshe: Commented on the manuscript. All authors reviewed the manuscript.
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Singh, A.S., Pathak, D., Devi, M.S. et al. Antibiotic alters host’s gut microbiota, fertility, and antimicrobial peptide gene expression vis-à-vis ampicillin treatment on model organism Drosophila melanogaster. Int Microbiol (2024). https://doi.org/10.1007/s10123-024-00507-9
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DOI: https://doi.org/10.1007/s10123-024-00507-9