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Author(s) Sample Study Design Results Conclusion Azad, Bridgman, Becker & Kozyrskyj, 2014. 1 629 children examined at age 9 and 12 in SAGE study Secondary analysis of provincial health care database in 1995 SAGE cohort study Antibiotic exposure in the first year of like was more positively associated with the development of overweight in childhood compared to unexposed groups (P= 0.002) Antibiotic exposure in first year of life significantly increased risk of overweight and central adiposity in boys ages 9 and 12. Scott et al., 2016. 12 21714 children in Health Improvement Network (Dataset from UK medical records (1995- 2012) Retrospective cohort study within Health Improvement Network Dataset Antibiotic exposure associated with increased risk of obesity at 4 years (OR=1.21) Antibiotic exposure within first 2 years of life is associated with 1.2% absolute and 25% relative increase in risk of early childhood obesity Risk of childhood obesity heightened when 3 or more courses of antibiotics were administered to children under the age of 2. Turta & Rautava, 2016. 9 Various studies Literature review An outcome of obesity is associated with an increased abundance of phylum Firmucutes and decrease in Bacteriodetes High concentration of intestional bididobacteria may be associated with lower risk of overweight Prolonged gut microbiota alterations may be the result of repeated antibiotic exposure. Changes in gut microbiota composition associated with development of overweight and obesity. Edmonson & Eickhoff, 2017. 11 2-year study involving 607 children (aged 2-71 months) enrolled from 2007-2011 Secondary analysis of data from RCT Intervention for Children with Vesicoureteral Reflux Study No significant evidence that prolonged exposure to antibiotic TPM/SMX affected weight gain or outcomes of overweight or obesity in healthy infants and young children The link between prolonged antibiotic use and weight gain remains doubtful. Existing studies lack consistency and precision with respect to many variables: age, sex and antibiotic exposure details, etc. Mbakwa et al., 2016. 14 3030 caucasian women pregnant women (34 weeks gestation) recruited Total 979 children were eligible for analysis Cohort study β-lactam antibiotics were associated with an increase in weight z-scores during the follow-up period of the study Children exposed to a single course of antibiotics during the first 6 months of life showed an increase in weight gain compared to those who had no exposure. No association between single exposure of antibiotics and obesity between 6-12 months of age Association to obesity was present after single dose of antibiotics during first 6 months of life. Shao et al., 2017. 15 15 cohort studies involving 445 880 participants in developed countries Systematic review & meta-analysis Early life antibiotic exposure significantly increased risk of childhood overweight (RR=1.23) and obesity (RR=1.21) and BMI (mean difference: 0.07) 7% increase in risk of overweight (RR = 1.07) and 6& increase in risk for obesity (RR=1.06) with each additional course of antibiotics Early life antibiotic exposure significantly increased risk of childhood overweight and obesity. Cox & Blaser, 2015. 16 Samples from various studies Literature review Early life antibiotic exposure can disrupt gut microbiota development and can influence body mass (weight gain or stunted growth) These exposures impact body mass in adulthood Examining early life characteristics of gut microbiota could shed light on possible interventions directed at mitigating risks associated with obesity. Pihl et al., 2016. 13 Samples from various studies Systematic literature review Array of factors influence the gut microbiota profile (host genetics, delivery method, diet, age, environment, antibiotics) Establishment of such factors can provide a basis for obesity prevention initiatives. Understanding the role of gut microbiota is paramount for targeting childhood obesity. Abstract Background: It has been reported that the use of antibiotics is associated with excessive weight gain or obesity in healthy infants. Current data suggest intestinal microbiota perturbation caused by antibiotic exposure in the perinatal period programs the host to assume an obesity-prone metabolic phenotype. However, there is a lack of evidence regarding the causal pathway given the multifactorial etiology of obesity. Objective: The objective of this study was to explore the significance of the association between antibiotic exposure during critical periods of infancy before the age of 2 and the development of obesity. Methodology: A structured literature review was conducted on databases Medline, Scopus, CINAHL and Google Scholar resulting in 8 pertinent articles. Queries “Infants AND Obesity AND Antibiotic Exposure AND Gut Microbiota” were searched and screened, and infants’ ages were restricted to 1-23 months. Results: Antibiotic exposure during critical periods of early development significantly influenced weight gain and the progression of obesity. Furthermore, marked differences in the composition of their microbiota were exhibited when compared to lean subjects. Few studies concluded that exposure was not consistently associated with increased body mass, while others restricted the association solely to male infants. Conclusion: Over-prescription of antibiotics during infancy not only causes resistance to potentially harmful organisms in the GI tract, but may also lead to a life-long risk for obesity by destroying healthy colonization of necessary bacteria. It is paramount that further research be performed in order to establish preventive measures of obesity and counteract unfavourable effects on microbiota. Research Question Is there a significant association between antibiotic exposure during critical periods of infancy before the age of 2 and the development of obesity? Introduction Childhood obesity is among the most urgent public health issues of the pediatric population. 1 Over the last 25 years, there has been a considerable rise in the number of Canadian children and youth who are overweight or obese. 2 Based on the World Health Organization guidelines, 31.5% of 5- to 17- year olds, an estimated 1.6 million Canadian children, were classified as overweight (19.8%) or obese (11.7%) from 2009 to 2011. 3 Furthermore, overweight and obese children are at a high risk of becoming obese adults as well as presenting adverse health consequences, which include cardiovascular disease, type 2 diabetes and several cancers. 4,5,6 Since the 1940s, antibiotics have been essential in reducing human morbidity and mortality. 7 However, recent studies have shown that increased susceptibility to obesity later in life has been associated with early exposure to antibiotics in healthy individuals. 8 Worldwide, antibiotics are among the most frequently used pharmaceuticals in infants and children. 9 By two years of age, children have on average received nearly three courses of antibiotics. 9 Antibiotics are often prescribed inappropriately despite a significant number of expert guidelines which advocate its limited use. 6 It has been estimated that 5% of neonates have received antibiotics, although the incidence of culture-proven sepsis in newborn infants is less than one in 1000 neonates. 9 As opposed to the relatively stable microbiota of an adult, the microbiota of an infant is considerably more variable and vulnerable to antibiotic perturbation. 7 The critical period of gut colonization appears in early postnatal life. 1 Thus, early administration of antibiotics may disrupt patterns of intestinal colonization and increase intestinal permeability (Figure 1). 7 Moreover, the host assumes an obesity-prone metabolic phenotype which alters the host’s response to specific microbial signals. 10 Although an association between antibiotic exposure and obesity in healthy infants and children has been reported, there is a lack of evidence regarding the exact causal pathway given the multifactorial etiology of obesity. 11,12 Figure 1. Increased intestinal permeability resulting in higher levels of lipopolysaccharides in systemic circulation, leading to a low-grade systemic inflammatory state. 13 Methods Methodology used: structured literature review Figure 2. Visual representation of literature review process. Keywords/Search Queries: “Infants” AND “Obesity OR Weight Gain” AND “antibiotic exposure” AND “gut bacteria” The Hidden Culprit: Predisposition to Obesity as a Result of Early-life Antibiotic Exposure Anupallavi Sinha 1 , Danielle Edmonds 1 , Rania Berjawi 1 , Sonia Hajo 1 University of Ottawa 1 Results Table 1: Synthesis of main findings from eight pertinent articles used for literature review Discussion All apart from one, studies demonstrated a marked, statistically significant association between early-life antibiotic exposure and the development of overweight or obesity. An increased proportion of Firmicutes to Bacteroidetes is recognized as a marker of obesity. 10 A greater number of courses of antibiotics was associated with a higher risk of developing childhood overweight or obesity. Also, obesity as a result from antibiotic exposure was observed in as little as 6 months from birth. Obesity during childhood can also carry on to adulthood. One study found a relationship between gut microbiota and obesity in only males only. 1 Some mechanisms established in mice models were excessive caloric intake, changes in adiposity, fatty acid metabolism, and regulation of peptide YY and GLP-1 secretion. 17 Multiple factors affect the development of gut microbiota, such as host genetics, delivery method, diet, age, and antibiotic use. Some preventative factors to obesity that have been observed in studies are breastfeeding, healthy diet, and physical activity, however when coupled with antibiotics they had no protective effects. 1 The direct mechanism if the microbiota action on adiposity alterations remain ill-detailed and poorly understood; however, mounting evidence points to the association between altered gut microbiota profiles and increased risk of obesity. Articles also emphasize the increasing need for preventative measures targeting childhood obesity. With a clearer understanding of the role of gut microbiota in the development of childhood obesity can aid in mitigating risks associated with the childhood epidemic. Limitations: Variables were adjusted to account for maternal age, pre-gravid BMI, birth weight, sex, delivery mode, etc. 12 Articles also attempted to avoid confounding by excluding smoking pregnant women from secondary analysis. 12 -Information biases in research where medical records lacked specific information on antibiotic exposure (use, dosage, number of courses, etc.) 11 - Recall bias was apparent in one study, as prenatal antibiotic use was determined by a questionnaire. 12 - The nature of the study forced a limited scope of pre-established data in the form of systematic reviews, literature reviews and secondary analyses; performing a randomized- controlled trial which administered antibiotics to humans for the purposes of experimentation is not ethically feasible. Conclusion It is presumed that the overprescription of antibiotics and its exposure during infancy significantly contributes to the modern prevalence of obesity due to its potentially harmful effects on the microbiota. However, further studies are needed to confirm these findings in order to establish preventative measures in the future. Future Directions To investigate • the association between antibiotics and the hunger hormone, ghrelin 18,19 • the association between antibiotics and the satiety hormone leptin 19 • the implementation of omega-3 fatty acids to combat obesity through the prevention of antibiotic-induced modulation of gut microbiota 20 • the anti-obesity effects of probiotics (Lactobacillus genus). 21 • the administration of prebiotics such as FOS, inulin, galacto-oligosaccharides (GOS) and lactulose to prevent and treat childhood obesity. 22 References Azad, M., Bridgman, S., Becker, A., & Kozyrskyj, A. (2014). Infant antibiotic exposure and the development of childhood overweight and central adiposity. International Journal of Obesity, 38(10), 1290. Shields, M. (2006). Overweight and obesity among children and youth. Health Reports, 17(3), 27-42. Roberts, K. C., Shields, M. A., De Groh, M., Aziz, A., & Gilbert, J. (2012). Overweight and obesity in children and adolescents: Results from the 2009 to 2011 Canadian Health Measures Survey. Health Reports / Statistics Canada, Canadian Centre for Health Information = Rapports Sur La Santé / Statistique Canada, Centre Canadien D'information Sur La Santé, 23(3), 37-41. Connor Gorber, S. S., Shields, M., Tremblay, M., & McDowell, I. (2008). The feasibility of establishing correction factors to adjust self-reported estimates of obesity. Health Reports / Statistics Canada, Canadian Centre for Health Information = Rapports Sur La Santé / Statistique Canada, Centre Canadien D'information Sur La Santé, 19(3), 71-82. De Onis, M., Onyango, A., Borghi, E., Siyam, A., Nishida, C., & Siekmann, J. (2007). Development of a WHO growth reference for school-aged children and adolescents. Bulletin of the World Health Organization, 85(9), 660-7. Ontario Agency for Health Protection Promotion, issuing body, & Canadian Electronic Library , distributor. (2013). Addressing obesity in children and youth : Evidence to guide action for Ontario (Canadian Electronic Library. Canadian health research collection). L Trasande, J Blustein, M Liu, E Corwin, L M Cox, & M J Blaser. (2012). Infant antibiotic exposures and early-life body mass. International Journal of Obesity,37(1), 16-23. Ianiro, G., Tilg, H., & Gasbarrini, A. (2016). Antibiotics as deep modulators of gut microbiota: Between good and evil. Gut, 65(11), 1906. Turta, O., & Rautava, S. (2016). Antibiotics, obesity and the link to microbes - what are we doing to our children? BMC Medicine, 14, BMC Medicine, 2016, Vol.14. Kaliannan, K., Wang, B., Li, X., Bhan, A., & Kang, J. (2016). Omega-3 fatty acids prevent early-life antibiotic exposure-induced gut microbiota dysbiosis and later-life obesity. International Journal of Obesity, 40(6), 1039. Edmonson, M., & Eickhoff, J. (2017). Weight Gain and Obesity in Infants and Young Children Exposed to Prolonged Antibiotic Prophylaxis. JAMA Pediatrics,171(2), 150-156. Scott, F. I., Horton, D. B., Mamtani, R., Haynes, K., Goldberg, D. S., Lee, D. Y., & Lewis, J. D. (2016). Administration of antibiotics to children before age 2 years increases risk for childhood obesity.Gastroenterology, 151(1), 120-129.e5. doi:10.1053/j.gastro.2016.03.006 Pihl, A., Fonvig, C., Stjernholm, T., Hansen, T., Pedersen, O., & Holm, J. (2016). The Role of the Gut Microbiota in Childhood Obesity. Childhood Obesity, 12(4), 292-299. Mbakwa, Scheres, Penders, Mommers, Thijs, & Arts. (2016). Early Life Antibiotic Exposure and Weight Development in Children. The Journal of Pediatrics, 176, 105-113.e2. Shao, X., Ding, X., Wang, B., Li, L., An, X., Yao, Q., ... & Zhang, J. A. (2017). antibiotic exposure in early life increases risk of childhood Obesity: a systematic review and Meta-analysis. Frontiers in endocrinology, 8, 170. Cox, L., & Blaser, M. (2015). Antibiotics in early life and obesity. 11(3), 182. Musso, G., Gambino, R., & Cassader, M. (2010). Obesity, Diabetes, and Gut Microbiota. Diabetes Care, 33(10), 2277-2284. Christine Delporte. (2013). Structure and Physiological Actions of Ghrelin. Scientifica, 2013, Scientifica, 01 January 2013, Vol.2013. Mbakwa, Scheres, Penders, Mommers, Thijs, & Arts. (2016). Early Life Antibiotic Exposure and Weight Development in Children. The Journal of Pediatrics, 176, 105-113.e2. Pihl, A., Fonvig, C., Stjernholm, T., Hansen, T., Pedersen, O., & Holm, J. (2016). The Role of the Gut Microbiota in Childhood Obesity. Childhood Obesity, 12(4), 292-299. Koleva, P., Bridgman, S., & Kozyrskyj, A. (2015). The Infant Gut Microbiome: Evidence for Obesity Risk and Dietary Intervention. Nutrients, 7(4), 2237-2260. Safavi, M., Farajian, S., Kelishadi, R., Mirlohi, M., & Hashemipour, M. (2013). The effects of synbiotic supplementation on some cardio-metabolic risk factors in overweight and obese children: A randomized triple-masked controlled trial. International Journal of Food Sciences and Nutrition, 2013, Vol.64(6), P.687-693,64(6), 687-693. Inclusion Criteria: Exclusion Criteria: Infants 1-23 months of age Infants over 23 months of age Articles written in English only Articles written in foreign languages Peer -reviewed articles Congenital illness or malformations Articles identified on databases: Medline, Google Scholar, CINAHL, & Scopus N = 19 Articles omitted based on accessibility of full text online N=1 Omitted After Screening N = 10 Total Studies Included N=8

The Hidden Culprit - Recherche uO Research: Home · Antibiotic exposure associated with increased risk of obesity at 4 years (OR=1.21) Antibiotic exposure within first 2 years of

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Page 1: The Hidden Culprit - Recherche uO Research: Home · Antibiotic exposure associated with increased risk of obesity at 4 years (OR=1.21) Antibiotic exposure within first 2 years of

Author(s) Sample StudyDesign Results ConclusionAzad,Bridgman,Becker&Kozyrskyj,2014.1

629childrenexaminedatage9and12inSAGEstudy

Secondaryanalysisofprovincialhealthcaredatabasein1995SAGEcohortstudy

Antibioticexposureinthefirstyearoflikewasmorepositivelyassociatedwiththedevelopmentofoverweightinchildhoodcomparedtounexposedgroups(P=0.002)

Antibioticexposureinfirstyearoflifesignificantlyincreasedriskofoverweightandcentraladiposityinboysages9and12.

Scottetal.,2016.12

21714childreninHealthImprovementNetwork(DatasetfromUKmedicalrecords(1995-2012)

RetrospectivecohortstudywithinHealthImprovementNetworkDataset

Antibioticexposureassociatedwithincreasedriskofobesityat4years(OR=1.21)Antibioticexposurewithinfirst2yearsoflifeisassociatedwith1.2%absoluteand25%relativeincreaseinriskofearlychildhoodobesity

Riskofchildhoodobesityheightenedwhen3ormorecoursesofantibioticswereadministeredtochildrenundertheageof2.

Turta&Rautava,2016.9

Variousstudies Literaturereview AnoutcomeofobesityisassociatedwithanincreasedabundanceofphylumFirmucutesanddecreaseinBacteriodetesHighconcentrationofintestionalbididobacteriamaybeassociatedwithlower riskofoverweight

Prolongedgutmicrobiotaalterationsmaybetheresultofrepeatedantibioticexposure.Changesingutmicrobiotacompositionassociatedwithdevelopmentofoverweightandobesity.

Edmonson&Eickhoff,2017.11

2-yearstudyinvolving607children(aged2-71months)enrolledfrom2007-2011

SecondaryanalysisofdatafromRCTInterventionforChildrenwithVesicoureteralRefluxStudy

NosignificantevidencethatprolongedexposuretoantibioticTPM/SMXaffectedweightgainoroutcomesofoverweightorobesityinhealthyinfantsandyoungchildren

Thelinkbetweenprolongedantibioticuseandweightgainremainsdoubtful.Existingstudieslackconsistencyandprecisionwithrespecttomanyvariables:age,sexandantibioticexposuredetails,etc.

Mbakwa etal.,2016.14

3030caucasianwomenpregnantwomen(34weeksgestation)recruitedTotal979childrenwereeligibleforanalysis

Cohortstudy β-lactamantibioticswereassociatedwithanincreaseinweightz-scoresduringthefollow-upperiodofthestudyChildrenexposedtoasinglecourseofantibioticsduringthefirst6monthsoflifeshowedanincreaseinweightgaincomparedtothosewhohadnoexposure.Noassociationbetweensingleexposureofantibioticsandobesitybetween6-12monthsofage

Associationtoobesitywaspresentaftersingledoseofantibioticsduringfirst6monthsoflife.

Shaoetal.,2017.15

15cohortstudiesinvolving445880participantsindevelopedcountries

Systematicreview&meta-analysis

Earlylifeantibioticexposuresignificantlyincreasedriskofchildhoodoverweight(RR=1.23)andobesity(RR=1.21)andBMI(meandifference:0.07)7%increaseinriskofoverweight(RR=1.07)and6&increaseinriskforobesity(RR=1.06)witheachadditionalcourseofantibiotics

Earlylifeantibioticexposuresignificantlyincreasedriskofchildhoodoverweightandobesity.

Cox&Blaser,2015.16

Samplesfromvariousstudies

Literaturereview Earlylifeantibioticexposurecandisruptgutmicrobiotadevelopmentandcaninfluencebodymass(weightgainorstuntedgrowth)Theseexposuresimpactbodymassinadulthood

Examiningearlylifecharacteristicsofgutmicrobiotacouldshedlightonpossibleinterventionsdirectedatmitigatingrisksassociatedwithobesity.

Pihletal.,2016.13

Samplesfromvariousstudies

Systematicliteraturereview

Arrayoffactorsinfluencethegutmicrobiotaprofile(hostgenetics,deliverymethod,diet,age,environment,antibiotics)

Establishmentofsuchfactorscanprovideabasisforobesitypreventioninitiatives.Understandingtheroleofgutmicrobiotaisparamountfortargetingchildhoodobesity.

AbstractBackground:Ithasbeenreportedthattheuseofantibioticsisassociatedwithexcessiveweightgainorobesityinhealthyinfants.Currentdatasuggestintestinalmicrobiotaperturbationcausedbyantibioticexposureintheperinatalperiodprogramsthehosttoassumeanobesity-pronemetabolicphenotype.However,thereisalackofevidenceregardingthecausalpathwaygiventhemultifactorialetiologyofobesity.Objective: Theobjectiveofthisstudywastoexplorethesignificanceoftheassociationbetweenantibioticexposureduringcriticalperiodsofinfancybeforetheageof2andthedevelopmentofobesity.Methodology:AstructuredliteraturereviewwasconductedondatabasesMedline,Scopus,CINAHLandGoogleScholarresultingin8pertinentarticles.Queries“InfantsANDObesityANDAntibioticExposureANDGutMicrobiota”weresearchedandscreened,andinfants’ageswererestrictedto1-23months.Results:Antibioticexposureduringcriticalperiodsofearlydevelopmentsignificantlyinfluencedweightgainandtheprogressionofobesity.Furthermore,markeddifferencesinthecompositionoftheirmicrobiotawereexhibitedwhencomparedtoleansubjects.Fewstudiesconcludedthatexposurewasnotconsistentlyassociatedwithincreasedbodymass,whileothersrestrictedtheassociationsolelytomaleinfants.Conclusion:Over-prescriptionofantibioticsduringinfancynotonlycausesresistancetopotentiallyharmfulorganismsintheGItract,butmayalsoleadtoalife-longriskforobesitybydestroyinghealthycolonizationofnecessarybacteria.Itisparamountthatfurtherresearchbeperformedinordertoestablishpreventivemeasuresofobesityandcounteractunfavourableeffectsonmicrobiota.

ResearchQuestionIsthereasignificantassociationbetweenantibioticexposureduringcriticalperiodsofinfancybeforetheageof2andthedevelopmentofobesity?

IntroductionChildhoodobesityisamongthemosturgentpublichealthissuesofthepediatricpopulation.1

Overthelast25years,therehasbeenaconsiderableriseinthenumberofCanadianchildrenandyouthwhoareoverweightorobese.2 BasedontheWorldHealthOrganizationguidelines,31.5%of5- to17- yearolds,anestimated1.6millionCanadianchildren,wereclassifiedasoverweight(19.8%)orobese(11.7%)from2009to2011.3 Furthermore,overweightandobesechildrenareatahighriskofbecomingobeseadultsaswellaspresentingadversehealthconsequences,whichincludecardiovasculardisease,type2diabetesandseveralcancers.4,5,6

Sincethe1940s,antibioticshavebeenessentialinreducinghumanmorbidityandmortality.7However,recentstudieshaveshownthatincreasedsusceptibilitytoobesitylaterinlifehasbeenassociatedwithearlyexposuretoantibioticsinhealthyindividuals.8 Worldwide,antibioticsareamongthemostfrequentlyusedpharmaceuticalsininfantsandchildren.9 Bytwoyearsofage,childrenhaveonaveragereceivednearlythreecoursesofantibiotics.9 Antibioticsareoftenprescribedinappropriatelydespiteasignificantnumberofexpertguidelineswhichadvocateitslimiteduse.6 Ithasbeenestimatedthat5%ofneonateshavereceivedantibiotics,althoughtheincidenceofculture-provensepsisinnewborninfantsislessthanonein1000neonates.9

Asopposedtotherelativelystablemicrobiotaofanadult,themicrobiotaofaninfantisconsiderablymorevariableandvulnerabletoantibioticperturbation.7 Thecriticalperiodofgutcolonizationappearsinearlypostnatallife.1 Thus,earlyadministrationofantibioticsmaydisruptpatternsofintestinalcolonizationandincreaseintestinalpermeability(Figure1).7 Moreover,thehostassumesanobesity-pronemetabolicphenotypewhichaltersthehost’sresponsetospecificmicrobialsignals.10 Althoughanassociationbetweenantibioticexposureandobesityinhealthyinfantsandchildrenhasbeenreported,thereisalackofevidenceregardingtheexactcausalpathwaygiventhemultifactorialetiologyofobesity.11,12

Figure1. Increasedintestinalpermeabilityresultinginhigherlevelsoflipopolysaccharidesinsystemiccirculation,leadingtoalow-gradesystemicinflammatorystate.13

MethodsMethodologyused: structuredliteraturereview

Figure2.Visualrepresentationofliteraturereviewprocess.

Keywords/SearchQueries: “Infants”AND“ObesityORWeightGain”AND“antibioticexposure”AND“gutbacteria”

The Hidden Culprit: PredispositiontoObesityasaResultofEarly-lifeAntibioticExposure

Anupallavi Sinha1,DanielleEdmonds1,RaniaBerjawi1,SoniaHajo1UniversityofOttawa1

ResultsTable1:Synthesisofmainfindingsfromeightpertinentarticlesusedforliteraturereview

DiscussionAllapartfromone,studiesdemonstratedamarked,statisticallysignificantassociationbetweenearly-lifeantibioticexposureandthedevelopmentofoverweightorobesity.AnincreasedproportionofFirmicutes toBacteroidetes isrecognizedasamarkerofobesity.10 Agreaternumberofcoursesofantibioticswasassociatedwithahigherriskofdevelopingchildhoodoverweightorobesity.Also,obesityasaresultfromantibioticexposurewasobservedinaslittleas6monthsfrombirth.Obesityduringchildhoodcanalsocarryontoadulthood.Onestudyfoundarelationshipbetweengutmicrobiotaandobesityinonlymalesonly.1 Somemechanismsestablishedinmicemodelswereexcessivecaloricintake,changesinadiposity,fattyacidmetabolism,andregulationofpeptideYYandGLP-1secretion.17 Multiplefactorsaffectthedevelopmentofgutmicrobiota,suchashostgenetics,deliverymethod,diet,age,andantibioticuse.Somepreventativefactorstoobesitythathavebeenobservedinstudiesarebreastfeeding,healthydiet,andphysicalactivity,howeverwhencoupledwithantibioticstheyhadnoprotectiveeffects.1 Thedirectmechanismifthemicrobiotaactiononadiposityalterationsremainill-detailedandpoorlyunderstood;however,mountingevidencepointstotheassociationbetweenalteredgutmicrobiotaprofilesandincreasedriskofobesity.Articlesalsoemphasizetheincreasingneedforpreventativemeasurestargetingchildhoodobesity.Withaclearerunderstandingoftheroleofgutmicrobiotainthedevelopmentofchildhoodobesitycanaidinmitigatingrisksassociatedwiththechildhoodepidemic.

Limitations:Variableswereadjustedtoaccountformaternalage,pre-gravidBMI,birthweight,sex,deliverymode,etc.12 Articlesalsoattemptedtoavoidconfoundingbyexcludingsmokingpregnantwomenfromsecondaryanalysis.12-Informationbiasesinresearchwheremedicalrecordslackedspecificinformationonantibioticexposure(use,dosage,numberofcourses,etc.)11- Recallbiaswasapparentinonestudy,asprenatalantibioticusewasdeterminedbyaquestionnaire.12- Thenatureofthestudyforcedalimitedscopeofpre-establisheddataintheformofsystematicreviews,literaturereviewsandsecondaryanalyses;performingarandomized-controlledtrialwhichadministeredantibioticstohumansforthepurposesofexperimentationisnotethicallyfeasible.

ConclusionItispresumedthattheoverprescriptionofantibioticsanditsexposureduringinfancy

significantlycontributestothemodernprevalenceofobesityduetoitspotentiallyharmfuleffectsonthemicrobiota.However,furtherstudiesareneededtoconfirmthesefindingsinordertoestablishpreventativemeasuresinthefuture.

FutureDirectionsToinvestigate• theassociationbetweenantibioticsandthehungerhormone,ghrelin18,19• theassociationbetweenantibioticsandthesatietyhormoneleptin19• theimplementationofomega-3fattyacidstocombatobesitythroughthepreventionof

antibiotic-inducedmodulationofgutmicrobiota 20

• theanti-obesityeffectsofprobiotics(Lactobacillusgenus).21• theadministrationofprebioticssuchasFOS,inulin,galacto-oligosaccharides(GOS)andlactulose

topreventandtreatchildhoodobesity.22

ReferencesAzad,M.,Bridgman,S.,Becker,A.,&Kozyrskyj,A.(2014).Infantantibioticexposureandthedevelopmentofchildhoodoverweightandcentraladiposity.InternationalJournalofObesity, 38(10),1290.Shields,M.(2006).Overweightandobesityamongchildrenandyouth.HealthReports, 17(3),27-42.Roberts,K.C.,Shields,M.A.,DeGroh,M.,Aziz,A.,&Gilbert,J.(2012).Overweightandobesityinchildrenandadolescents: Resultsfromthe2009to2011CanadianHealthMeasuresSurvey.HealthReports/StatisticsCanada,CanadianCentreforHealthInformation=RapportsSurLaSanté/Statistique Canada,CentreCanadien D'information SurLaSanté, 23(3),37-41.ConnorGorber,S.S.,Shields,M.,Tremblay,M.,&McDowell,I.(2008).Thefeasibilityofestablishingcorrectionfactorstoadjustself-reportedestimatesofobesity.HealthReports/StatisticsCanada,CanadianCentreforHealthInformation=RapportsSurLaSanté/Statistique Canada,CentreCanadien D'information SurLaSanté, 19(3),71-82.DeOnis,M.,Onyango,A.,Borghi,E.,Siyam,A.,Nishida,C.,&Siekmann,J.(2007).DevelopmentofaWHOgrowthreferenceforschool-agedchildrenandadolescents.BulletinoftheWorldHealthOrganization, 85(9),660-7.OntarioAgencyforHealthProtectionPromotion,issuingbody,&CanadianElectronicLibrary,distributor.(2013).Addressingobesityinchildrenandyouth:EvidencetoguideactionforOntario(CanadianElectronicLibrary.Canadianhealthresearchcollection).LTrasande,JBlustein,MLiu,ECorwin,LMCox,&MJBlaser.(2012).Infantantibioticexposuresandearly-lifebodymass.InternationalJournalofObesity,37(1),16-23.Ianiro,G.,Tilg,H.,&Gasbarrini,A.(2016).Antibioticsasdeepmodulatorsofgutmicrobiota:Betweengoodandevil.Gut, 65(11),1906.Turta,O.,&Rautava,S.(2016).Antibiotics,obesityandthelinktomicrobes- whatarewedoingtoourchildren?BMCMedicine, 14,BMCMedicine,2016,Vol.14.Kaliannan,K.,Wang,B.,Li,X.,Bhan,A.,&Kang,J.(2016).Omega-3fattyacidspreventearly-lifeantibioticexposure-inducedgutmicrobiotadysbiosis andlater-lifeobesity.InternationalJournalofObesity, 40(6),1039.Edmonson,M.,&Eickhoff,J.(2017).WeightGainandObesityinInfantsandYoungChildrenExposedtoProlongedAntibioticProphylaxis.JAMAPediatrics,171(2),150-156.Scott,F.I.,Horton,D.B.,Mamtani,R.,Haynes,K.,Goldberg,D.S.,Lee,D.Y.,&Lewis,J.D.(2016).Administrationofantibioticstochildrenbeforeage2yearsincreasesriskforchildhoodobesity.Gastroenterology,151(1),120-129.e5.doi:10.1053/j.gastro.2016.03.006Pihl,A.,Fonvig,C.,Stjernholm,T.,Hansen,T.,Pedersen,O.,&Holm,J.(2016).TheRoleoftheGutMicrobiotainChildhoodObesity.ChildhoodObesity, 12(4),292-299.Mbakwa,Scheres,Penders,Mommers,Thijs,&Arts.(2016).EarlyLifeAntibioticExposureandWeightDevelopmentinChildren.TheJournalofPediatrics, 176,105-113.e2.Shao,X.,Ding,X.,Wang,B.,Li,L.,An,X.,Yao,Q.,...&Zhang,J.A.(2017).antibioticexposureinearlylifeincreases riskofchildhoodObesity:asystematicreviewandMeta-analysis.Frontiersinendocrinology,8,170.Cox,L.,&Blaser,M.(2015).Antibioticsinearlylifeandobesity.11(3),182.Musso,G.,Gambino,R.,&Cassader,M.(2010).Obesity,Diabetes,andGutMicrobiota.DiabetesCare, 33(10),2277-2284.ChristineDelporte.(2013).StructureandPhysiologicalActionsofGhrelin.Scientifica, 2013,Scientifica,01January2013,Vol.2013.Mbakwa,Scheres,Penders,Mommers,Thijs,&Arts.(2016).EarlyLifeAntibioticExposureandWeightDevelopmentinChildren.TheJournalofPediatrics, 176,105-113.e2.Pihl,A.,Fonvig,C.,Stjernholm,T.,Hansen,T.,Pedersen,O.,&Holm,J.(2016).TheRoleoftheGutMicrobiotainChildhoodObesity.ChildhoodObesity, 12(4),292-299.Koleva,P.,Bridgman,S.,&Kozyrskyj,A.(2015).TheInfantGutMicrobiome:EvidenceforObesityRiskandDietaryIntervention.Nutrients, 7(4),2237-2260.Safavi,M.,Farajian,S.,Kelishadi,R.,Mirlohi,M.,&Hashemipour,M.(2013).Theeffectsofsynbiotic supplementationonsomecardio-metabolicriskfactorsinoverweightandobesechildren:Arandomizedtriple-maskedcontrolledtrial.InternationalJournalofFoodSciencesandNutrition,2013,Vol.64(6),P.687-693,64(6),687-693.

InclusionCriteria: ExclusionCriteria:Infants1-23monthsofage Infantsover23monthsofage

ArticleswritteninEnglishonly Articleswritteninforeignlanguages

Peer-reviewedarticles Congenitalillnessormalformations

Articlesidentifiedondatabases:Medline,GoogleScholar,CINAHL,&

ScopusN=19

Articlesomittedbasedonaccessibilityoffulltext

onlineN=1

OmittedAfterScreeningN=10

TotalStudiesIncludedN=8

129 inflammation and culprit lesions

129 inflammation and culprit lesions

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