Anderson, J.E. and J.E. Perry. 1996. Characterization of wetland ...
SPLASH! m ilks c en updat - Home - California Dairy...
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• This month's issue features dairy and defense against kidney disease, human milk oligosaccharides and immunity, Holder pasteurization’s impact on nutrients, and human milk oligosaccharides and Streptococcus. Dairy Consumption Reduces Risk of Kidney Disease • Habitual intake of low- or reduced-fat dairy products is associated with a lower risk for developing chronic kidney disease. • Dairy foods may influence kidney function because they lower the risk for developing hypertension and type 2 diabetes, the two leading causes for chronic kidney disease. • Dairy components, including calcium, magnesium, phosphorus, and protein, may directly influence kidney function by modifying inflammation and oxidative stress. Dairy foods are best known for promoting a healthy skeleton, but bones are not the only tissue to reap their health benefits. The very same dairy ingredients—calcium, magnesium, phosphorus, potassium, and protein—that build and maintain a healthy skeleton have demonstrated protective effects on cardiovascular disease, type 2 diabetes (T2D), and hypertension [1]. And now a growing body of evidence [1-6] suggests habitual dairy consumption may benefit the kidneys as well. Chronic kidney disease (CKD) currently affects 27 million adults in the U.S. [7] and nearly 10% of adults worldwide [8]. CKD is diagnosed based on a filtration rate—the glomerular filtration rate (GFR) to be exact—because the kidneys’ job is to filter the blood. Normal physiological functions, such as protein digestion and muscle activity, create waste products (e.g., urea, creatinine) that need to be removed from the blood and passed into urine. The GFR measures how much of this waste the body filters in a given amount of time. A normal GFR is between 90 and 120 milliliters of blood per minute [1, 7]. Although there is variation in what is considered normal with respect to age, sex, ethnicity, and body size, values below 90 ml/min are considered indicative of abnormal kidney function [7]. CKD is diagnosed when a patient has a GFR less than 60 ml/min for three or more months [1, 5, 7, 8]. The link between dairy foods and bone health is apparent; milk, cheese, and yogurt supply the very minerals needed to construct the skeleton. But how do the ingredients in dairy foods influence the kidneys’ ability to filter out waste? One potential pathway is indirect; that is, dairy components influence other physiological functions that directly affect renal function [1,2]. Currently, hypertension and T2D are the leading causes of CKD. Elevated blood pressure damages the blood vessels and the nephrons in the kidneys, weakening them and their ability to filter out waste products. Elevated blood sugar levels have a similar effect; by forcing the kidneys to work harder, T2D weakens the kidneys to the point where they pass nutrients the body needs (such as the protein albumin) into urine along with waste products [7]. Indeed, increased albumin in urine, a condition referred to as albuminuria, is itself diagnostic of CKD. Consumption of dairy foods has been linked to a reduced risk for both hypertension and T2D [9-13]. By keeping blood pressure and blood sugar in check, it stands to reason that dairy also may modify the risk for developing CKD. Indeed, diets designed to lower blood pressure have also demonstrated a protective effect for CKD [3-5]. The DASH diet (Dietary Approaches to Stop Hypertension) focuses on eight food components: high intakes of fruit, vegetables, nuts, legumes, and low-fat dairy combined with low intakes of sodium, sweetened beverages, and red/processed meats [3]. The health benefits conferred by this diet on both blood pressure and cardiovascular disease are attributed to the additive effects of the food components. That is, it is not simply one food ingredient that improves vascular health but the synergistic actions of all ingredients [3]. Viewed this way, dairy foods are part of a larger dietary strategy to improve health including kidney disease but are not themselves the focus of the studies. Nevertheless, a 23-year study of nearly 15,000 middle-aged American men and women [3] identified a lower risk for kidney disease in participants with a higher dairy product intake. Legume and nut intake also demonstrated a protective effect against CKD, whereas consumption of red/processed meat increased CKD risk [3]. These results were echoed in a six-year study on 1600 Middle Eastern adults [4]. Study participants that did better at sticking to the DASH diet, including higher consumption of dairy foods, had lower odds for developing CKD. In both DASH diet studies [3,4], lower CKD risk was not only attributed to what the participants were eating more of but also what they were eating less of (i.e., sodium, red meat, and sugary drinks). Thus, it is not possible to say whether low-fat dairy foods would have had a protective effect (or as significant of an effect) in the absence of the other components of the DASH diet. It also is possible that dairy foods directly influence the health of the kidneys through their anti-inflammatory and antioxidant SPLASH! ® milk science update August 2017 Issue
Transcript of SPLASH! m ilks c en updat - Home - California Dairy...
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This month's issue features dairy and defense against kidney disease, human milk oligosaccharides and immunity, Holder pasteurization’s impact on nutrients, and human milk oligosaccharides and Streptococcus. DairyConsumptionReducesRiskofKidneyDisease
• Habitualintakeoflow-orreduced-fatdairyproductsisassociatedwithalowerriskfordevelopingchronickidneydisease.
• Dairyfoodsmayinfluencekidneyfunctionbecausetheylowertheriskfordevelopinghypertensionandtype2diabetes,thetwoleadingcausesforchronickidneydisease.
• Dairycomponents,includingcalcium,magnesium,phosphorus,andprotein,maydirectlyinfluencekidneyfunctionbymodifyinginflammationandoxidativestress.
Dairyfoodsarebestknownforpromotingahealthyskeleton,butbonesarenottheonlytissuetoreaptheirhealthbenefits.Theverysamedairyingredients—calcium,magnesium,phosphorus,potassium,andprotein—thatbuildandmaintainahealthyskeletonhavedemonstratedprotectiveeffectsoncardiovasculardisease,type2diabetes(T2D),andhypertension[1].Andnowagrowingbodyofevidence[1-6]suggestshabitualdairyconsumptionmaybenefitthekidneysaswell.Chronickidneydisease(CKD)currentlyaffects27millionadultsintheU.S.[7]andnearly10%ofadultsworldwide[8].CKDisdiagnosedbasedonafiltrationrate—theglomerularfiltrationrate(GFR)tobeexact—becausethekidneys’jobistofiltertheblood.Normalphysiologicalfunctions,suchasproteindigestionandmuscleactivity,createwasteproducts(e.g.,urea,creatinine)thatneedtoberemovedfromthebloodandpassedintourine.TheGFRmeasureshowmuchofthiswastethebodyfiltersinagivenamountoftime.AnormalGFRisbetween90and120millilitersofbloodperminute[1,7].Althoughthereisvariationinwhatisconsiderednormalwithrespecttoage,sex,ethnicity,andbodysize,valuesbelow90ml/minareconsideredindicativeofabnormalkidneyfunction[7].CKDisdiagnosedwhenapatienthasaGFRlessthan60ml/minforthreeormoremonths[1,5,7,8].Thelinkbetweendairyfoodsandbonehealthisapparent;milk,cheese,andyogurtsupplytheverymineralsneededtoconstructtheskeleton.Buthowdotheingredientsindairyfoodsinfluencethekidneys’abilitytofilteroutwaste?
Onepotentialpathwayisindirect;thatis,dairycomponentsinfluenceotherphysiologicalfunctionsthatdirectlyaffectrenalfunction[1,2].Currently,hypertensionandT2DaretheleadingcausesofCKD.Elevatedbloodpressuredamagesthebloodvesselsandthenephronsinthekidneys,weakeningthemandtheirabilitytofilteroutwasteproducts.Elevatedbloodsugarlevelshaveasimilareffect;byforcingthekidneystoworkharder,T2Dweakensthekidneystothepointwheretheypassnutrientsthebodyneeds(suchastheproteinalbumin)intourinealongwithwasteproducts[7].Indeed,increasedalbumininurine,aconditionreferredtoasalbuminuria,isitselfdiagnosticofCKD.ConsumptionofdairyfoodshasbeenlinkedtoareducedriskforbothhypertensionandT2D[9-13].Bykeepingbloodpressureandbloodsugarincheck,itstandstoreasonthatdairyalsomaymodifytheriskfordeveloping
CKD.Indeed,dietsdesignedtolowerbloodpressurehavealsodemonstratedaprotectiveeffectforCKD[3-5].TheDASHdiet(DietaryApproachestoStopHypertension)focusesoneightfoodcomponents:highintakesoffruit,vegetables,nuts,legumes,andlow-fatdairycombinedwithlowintakesofsodium,sweetenedbeverages,andred/processedmeats[3].Thehealthbenefitsconferredbythisdietonbothbloodpressureandcardiovasculardiseaseareattributedtotheadditiveeffectsofthefoodcomponents.Thatis,itisnotsimplyonefoodingredientthatimprovesvascularhealthbutthesynergisticactionsofallingredients[3].Viewedthisway,dairyfoodsarepartofalargerdietarystrategytoimprovehealthincludingkidneydiseasebutarenotthemselvesthefocusofthestudies.Nevertheless,a23-yearstudyofnearly15,000middle-agedAmericanmenandwomen[3]identifiedalowerriskforkidneydiseaseinparticipantswithahigherdairyproductintake.LegumeandnutintakealsodemonstratedaprotectiveeffectagainstCKD,whereasconsumptionofred/processedmeatincreasedCKDrisk[3].Theseresultswereechoedinasix-yearstudyon1600MiddleEasternadults[4].StudyparticipantsthatdidbetteratstickingtotheDASHdiet,includinghigherconsumptionofdairyfoods,hadloweroddsfordevelopingCKD.InbothDASHdietstudies[3,4],lowerCKDriskwasnotonlyattributedtowhattheparticipantswereeatingmoreofbutalsowhattheywereeatinglessof(i.e.,sodium,redmeat,andsugarydrinks).Thus,itisnotpossibletosaywhetherlow-fatdairyfoodswouldhavehadaprotectiveeffect(orassignificantofaneffect)intheabsenceoftheothercomponentsoftheDASHdiet.Italsoispossiblethatdairyfoodsdirectlyinfluencethehealthofthekidneysthroughtheiranti-inflammatoryandantioxidant
SPLASH!® milkscienceupdateAugust2017Issue
properties[1].OxidativestressandinflammationareriskfactorsforCKDandfornumerousotherchronicdiseases,includingcancer,T2D,hypertension,andcardiovasculardisease.Calcium,magnesium,vitaminsAandE,dairyproteins,andevendairyfatshavedemonstratedantioxidantandanti-inflammatoryproperties.Thus,itcouldbemultipledairyingredients,ortheeffectoftheirsynergisticactions,influencingkidneyfunction.Supportforadirecteffectofdairyonthekidneyscomesfroma2016study[2]onnearly4000Dutchadults(aged25–65)withnormalormildlydecreasedGFR.ThemetricofinterestwaschangedinGFRoveranextendedperiodoftime,andeachsubjecthadthreeormoreexaminationsatfive-yearintervalsfrom1993to2012.Thestudyauthorsfoundthatahigherconsumption(definedas≥2servingperday)ofmilkandlow-fatdairyproductswasassociatedwithasmallerdeclineinGFRperyear.BecausethestudyauthorscontrolledforhypertensionandT2Dintheirstatisticalanalyses,theobservedprotectiveeffectofdairyconsumption,albeitminor(0.11ml/minperyearlessdecline),wasattributeddirectlytotheactionsofdairycomponents,suchascalcium,magnesium,andunsaturatedfats[2].OnedrawbackofthisstudywasthatitdidnotlookattheinfluenceofdairyfoodsonkidneyfunctioninindividualsdiagnosedwithCKD,makingitdifficulttosaywhethertheactionsofdairyingredientsinfluencekidneyfunctioninallindividualsoronlythosewithnormalorslightlyimpairedkidneyfunction.Thisissuewasaddressed,however,inastudy[1]publishedjustonemonthaftertheDutchstudy[2].Gopinathandcolleagues[1]reportontheassociationbetweendairyfoodconsumption,calciumintake,andCKDoveraten-yearstudyperiodin1185AustralianadultslivinginthesameareajustwestofSydney.BaselineGFRvalueswerenotusedforinclusioninthestudy,andthusthesevaluesvariedacrossparticipantsfromwithinthenormalrangetodiagnosticofCKD.LiketheDutchstudy[2],Gopinathetal.[1]foundthatconsuming≥2servingsoflow-fatdairyfoodsperdaywasassociatedwithareducedprevalenceandincidenceofCKDduringthestudyperiod,independentofhypertensionandT2D.ThisstudyalsocomparedcalciumintaketoCKDprevalenceandfoundthatindividualswhohadmorecalciumintheirdietwerelesslikelytohaveCKDoverthestudyperiod[1].Thus,theobservedprotectiveeffectoflow-fatdairyfoodsisatleastpartlyduetotheanti-inflammatoryandantioxidantpropertiesofcalcium.Inthesamestudypopulation,poorcalciumintakewasassociatedwithabnormalbloodvesselsintheretina,andtheauthorshypothesizethatasimilarphysiologicalresponsemaybetakingplaceinthekidneys,whereincalciuminfluencesrenalbloodvesselhealth[1].Importantly,dairy(andcalcium)intakeswerebelowtherecommendeddailyintakevaluesfor83%oftheparticipants[1],suggestingthatevenmoderatecalciumconsumptioncaninfluencekidneyfunction.Asobservationalstudies,neithertheDutch[2]northeAustralian[1]studywasabletoestablishacause-and-effectrelationshipbetweendairycomponentsandkidneyhealth.Butwhenthesestudiesarecombinedwithnumerousothersthatindicateaprotectiveeffectofdairyfoodconsumptiononthedevelopmentofchronicdiseases[9-13],itprovidesastrongframeworkfordevelopingmorerigorouscontrolledstudies.WiththerapidincreaseintheincidenceofCKDandotherchronicdiseases,itisencouragingthateasy-to-implementlifestylechanges,suchaseatingtwoormoreservingsoflow-fatdairyfoodsperday,couldhavesuchprofoundhealthbenefits.
GopinathB.,HarrisD.C.,FloodV.M.,BurlutskyG.,MitchellP.2016.Associationsbetweendairyfoodconsumptionandchronickidneydiseaseinolderadults.ScientificReports6,39532.doi:10.1038/srep39532
Herber-GastG.C.M.,BiesbroekS.,VerschurenW.M.M.,StehouwerC.D.A.,GansevoortR.T.,BakkerS.J.L.,SpijkermanA.M.W.2016.Associationofdietaryproteinanddairyintakesandchangeinrenalfunction:resultsfromthepopulation-basedlongitudinalDoetinchemcohortstudy.AmericanJournalofClinicalNutrition104:1712-1719.
RebholzC.M.,CrewsD.C.,GramsM.E.,SteffanL.M.,LeveyA.S.,MillerE.R.III,AppelL.J.,CoreshJ.2016.DASH(DietaryApproachestoStopHypertension)dietandriskofsubsequentkidneydisease.AmericanJournalofKidneyDisease68:853-861.
AsghariG.,YuzbashianE.,MirmiranP.,AziziF.2017.TheassociationbetweenDietaryApproachestoStopHypertensionandincidenceofchronickidneydiseaseinadults:theTehranLipidandGlucoseStudy.Nephrology,Dialysis,Transplantation32:ii224-ii230.
AsghariG.,FarhadnejadH.,MiriranP.,DizaviA.,YuzbashianE.,AziziF.2016.AdherencetotheMediterraneandietisassociatedwithreducedriskofchronickidneydiseasesamongTehranianadults.HypertensionResearch.doi:10.1038/hr.2016.98
HaringB.,SelvinE.,LiangM.,CoreshJ.,GramsM.E.,Petruski-IvlevaN.,SteffenL.M.,RebholzC.M.2016.Dietaryproteinsourcesandriskforincidentchronickidneydisease:resultsfromtheAtherosclerosisRiskinCommunities(ARIC)Study.JournalofRenalNutrition4(2017):233-42.
BaumgartenM.,GehrT.2011.Chronickidneydisease:detectionandevaluation.AmericanFamilyPhysician84:1138-1148. NationalKidneyFoundation:https://www.kidney.org/kidneydisease/global-facts-about-kidney-disease WangL.,MansonJ.E.,BuringJ.E.,LeeI-M.,SessoH.D.2008.Dietaryintakeofdairyproducts,calcium,andvitaminDandtheriskofhypertensioninmiddle-aged
andolderwomen.Hypertension51:1073-1079. RalstonR.A.,LeeJ.H.,TrubyH.,PalermoC.E.,WalerK.Z.2012.Asystematicreviewandmeta-analysisofelevatedbloodpressureandconsumptionofdairyfoods.JournalofHumanHypertension26:3-13
ComerfordK.B.,PasinG.2016.Emergingevidencefortheimportanceofdietaryproteinsourceonglucoregulatorymarkersandtype2diabetes:Differenteffectsofdairy,meat,fish,egg,andplantproteinfoods.Nutrients8:446;doi:10.3390/nu8080446
BallardK.D.,BrunoR.S.2015.Protectiveroleofdairyanditsconstituentsonvascularfunctionindependentofbloodpressure–loweringactivities.NutritionReview73:36-50.
AuneD.,NoratT.,RomundstadP.,VattenL.J.2013.Dairyproductsandtheriskoftype2diabetes:asystematicreviewanddose-responsemeta-analysisofcohortstudies.TheAmericanJournalofClinicalNutrition,ajcn-059030.
ContributedbyDr.LaurenMilliganNewmarkResearchAssociateSmithsonianInstitute
HumanMilkOligosaccharidesAlterImmuneCellPopulationsinPigs• Anewstudyexaminestheeffectsofhumanmilkoligosaccharides(HMOs)andprebioticoligosaccharidesonimmunecell
populationsinuninfectedandrotavirus-infectedpiglets.• ThestudyfoundthatdietaryHMOsalteredsystemicandgastrointestinalimmunecellpopulationsinpiglets,andhada
greatereffectonimmunecellsthanprebioticoligosaccharides.• DietaryHMOswerepreviouslyshowntohavesomeeffectsonrotavirusinfectionsusceptibility,andthestudysuggests
thatHMO-associatedchangestoimmunecellpopulationsmaymediatesomeoftheseeffects.Rotavirusisamajorviralpathogen,androtavirus-associateddiarrheaisprevalentinmanydevelopingcountries[1-4].Interestingly,breastfedinfantshavealowerincidenceofrotavirusinfectionthanformula-fedinfants,suggestingthatcertaincomponentsofhumanmilkmayhaveprotectiveeffectsagainstthisvirus[5].“Humanmilkisbest,you’regoingtohavethebestprotectionifyou’reabletofeedyourbabyhumanmilk,”saysProfessorSarahComstockofMichiganStateUniversity.“We’realwaysinterestedinhowwecanimprovetheimmuneresponsesofformula-fedinfantstomakethemmorelikethoseofhuman-milkfedinfants,”shesays.Researchershaveinvestigatedwhethersugarsfoundinhumanmilk,calledhumanmilkoligosaccharides(HMOs),mightberesponsibleforsomeoftheprotectiveeffectsagainstrotavirus.HMOsareabsentfrommostinfantformulasandhaveantimicrobialandimmunomodulatoryactionsinvitro[6-8].InanewstudyconductedbyComstockandProfessorSharonDonovanoftheUniversityofIllinois,theresearchersmeasuredtheeffectsofHMOsonimmunecellpopulationsfromuninfectedandrotavirus-infectedpigs[9].TheyalsocomparedtheeffectsofHMOswiththoseofprebioticoligosaccharides.“Wewantedthatcomparisongroupintherebecauseprebioticswerealreadybeingaddedtoinfantformula,anditdoesn’tmakemuchsensetospendalotofeffortandmoneyaddingHMOstoformulaifprebioticscanbejustaseffective,”saysComstock.TheresearchersfoundthatdietaryHMOsalteredsystemicandgastrointestinalimmunecellpopulationsinpigs,andhadagreatereffectonimmunecellsthandidprebiotics.ThefindingssuggestthattheHMO-associatedchangeinimmunecellpopulationsmaymediateprotectiveeffectsofHMOsonrotavirusinfection.“It’sjustmoreevidencethatbreastfeedingreallyisgoodforyourbaby,”saysComstock.
ResearchershavelongbeeninterestedinstudyingtheeffectsofHMOsontheimmunesystem,butit’sonlyrecentlythattheyhavebeenabletocost-effectivelyconductsuchstudies.“Upuntilthemid-2000s,eventhoughtherewasaninterestinthehumanmilkoligosaccharides,itwasreallyhardtocost-effectivelysynthesizethemortogetaccesstoenoughHMOstodothesetypesofexperiments,”saysComstock.“Itfinallyseemedfeasibletodothistypeofstudy,toactuallyfeedasignificantamountofhumanmilkoligosaccharidestopigletsandlookathowitaffectedtheirresponsetoinfection,”shesays.ComstockandDonovandecidedtotesttheeffectsofHMOsonrotavirusinfectioninapigletmodel,whoseimmuneandgastrointestinalsystemssharemanysimilaritieswiththoseofhumans.“Whenyoucombinetheimmunehomologywiththisgastrointestinalhomology,andyou’relooking
atagastrointestinalvirus,Ithinkit’sjustreallythebestsystem,”saysComstock.“Thepayoffintermsofusingthistypeofmodel,whichissomuchclosertoahumanthanusingarodentmodel,ishuge,”shesays.“Ithinkwe’llbegintoseemoreworkinhumansandIthinkyou’llseethatthepigletresearchreallyisanimportantdriverofwhatwemightexpectinthosehumanstudies,”saysComstock.ThenewstudybuildsonseveralpreviousstudiesbyComstockandDonovanlookingattheinteractionofHMOs,rotavirusandtheimmunesystem[7,8,10].“WeknewinvitrothatHMOswereabletoinhibitrotavirusinfectivity,”saysComstock.“WehadalotofevidencethatthereweredirectinteractionsofHMOswithrotavirus,whichwerepreventingrotavirusfromgettingaccesstotheintestinalepithelium,”shesays.“ThenwehadevidencethatfeedingHMOswoulddefinitelyaffectthetypesofmicrobesthatwerelivingintheintestine,andweadditionallyhadevidencethatHMOscoulddirectlyaffectimmunecellsexvivo,”saysComstock.“Wewantedtoputthisalltogetherandask,aretheseeffectshappeninginvivo,”shesays.Inthenewstudy,Comstockandhercolleaguescomparedtheimmunecellpopulationsofuninfectedandrotavirus-infectedpigsfedeitheracontrolformula,amixofHMOsconsistingof2’-fucosyllactose,lacto-N-neotetraose,6’-sialyllactose,3’-sialyllactose,andfreesialicacid,orprebioticsconsistingofshort-chaingalactooligosaccharidesandlong-chainfructooligosaccharides.BothinfectedanduninfectedHMO-fedpigshadincreasedperipheralbloodmononuclearcellnaturalkillercellsandmesentericlymphnodememoryeffectorTcellscomparedwithpigsfedformula.TheresearchersalsofoundthatdietaryprebioticsinducedintermediateincreasesinimmunecellpopulationscomparedwithdietaryHMOs.PrebioticoligosaccharidesmaybelesseffectivethanHMOsbecauseofdifferencesintheirstructuresorintheintestinalbacteriatheyaffect.
TheresearchersconcludedthatdietaryHMOsweremoreeffectivethanprebioticsinalteringsystemicandgastrointestinalimmunecellsinpigs.ComstocksuggeststhattheHMO-associatedchangestoimmunecellpopulationsmaymediatetheeffectsofdietaryHMOsonrotavirusinfectionsusceptibility.Comstocknotesthatthecurrentstudyonlylookedattheeffectsof5HMOstructuresoutofthemorethan200HMOsidentifiedsofar.“EvenfromthislimitedcomplementofHMOstructures,we’reabletogetincreasedimmuneresponsiveness,soimaginewhatitmightbelikeifyouwereabletoincludeafullcomplementofthese200-plusstructures,”shesays.“Obviouslyitwouldbeniceifwecouldgetall200intoinfantformula;themorewecanmakeinfantformulalookstructurallylikehumanmilk,Ithinkthebetteroffthosebabies’immunesystemswillbe,”saysComstock.“Unfortunately,alotofthoseareevenmoreexpensiveorimpossibletosynthesizeorextract,”shesays.Follow-upstudiescouldlookattheimmuneeffectsofHMOsinmoredetail,includinganalyzingtheireffectsatdifferentpost-infectiontimepoints.“Onelimitationofthisstudyisthatwehadtopickonetimepointtolookattheseeffects,”saysComstock.“ThatdoeslimitourknowledgeintermsofthefullcomplementofeffectsthatHMOscanhaveontheimmuneresponse,”shesays.TheresearchersplantofurtheranalyzetheirdatatotrytobetterunderstandhowtheHMOsaffectrotavirus-infectedpiglets.UnderstandingtheinvivoeffectsofHMOscouldhelpresearchersdesignimprovedinfantformulasandfindwaystoprotectagainstortreatrotavirusinfection.“Wedoplantodomoredetailedandsophisticatedmodelingofourdatasetstoseeifwecangainanyknowledgeorgenerateanyhypothesesabouthowthebacterialchangesandtheimmunesystemchangesareworkingtogethertoresolvetheinfectionandaltertheclinicalresponse,”saysComstock.“Thequestionis,canwemodelthoseinteractionstounderstandmorefullywhat’sgoingontoreducethelengthofdiarrheaintherotavirus-challengedpiglets,”shesays.FuturestudiescouldalsotrytodecipherthemechanismbywhichHMOsinfluenceimmunecellpopulations.“Itwouldbegreattoreallyunderstandthemechanismsofwhatishappening,”saysComstock.“Wedon’tknowiftheseHMOsaredirectlyinteractingwithimmunecellreceptorsanddirectlytriggeringthesechangesintheimmunecells,orifthroughinteractionswithbacteriaorvirusesintheintestinethey’remodulatingtheextentoftheimmuneresponsethatneedstohappen,”shesays.“Sothere’sstillablackboxbetweenfeedingoftheHMOsandtheclinicalresponse,butthisstudygivesussomecluesaboutwhatmightbegoingon”saysComstock.
BucardoF.,NordgrenJ.ImpactofvaccinationonthemolecularepidemiologyandevolutionofgroupArotavirusesinLatinAmericaandfactorsaffectingvaccineefficacy.InfectGenetEvol.2015Aug;34:106-13.
TateJ.E.,ParasharU.D.Rotavirusvaccinesinroutineuse.ClinInfectDis.2014Nov1;59(9):1291-301. Bar-ZeevN.,KapandaL.,TateJ.E.,JereK.C.,Iturriza-GomaraM.,NakagomiO.,MwansamboC.,CostelloA.,ParasharU.D.,HeydermanR.S.,FrenchN.,Cunliffe
N.A.;VacSurvConsortium.EffectivenessofamonovalentrotavirusvaccineininfantsinMalawiafterprogrammaticroll-out:anobservationalandcase-controlstudy.LancetInfectDis.2015Apr;15(4):422-8.
LiuX.,MengL.,LiJ.,LiuX.,BaiY.,YuD.,RenX.,LiuH.,ShenX.,WangP.,HuX.,WeiK.,PeiH.,KangQ.Etiologicalepidemiologyofviraldiarrheaonthebasisofsentinelsurveillanceinchildrenyoungerthan5yearsinGansu,northwestChina,2009-2013.JMedVirol.2015Dec;87(12):2048-53.
Plenge-BönigA.,Soto-RamírezN.,KarmausW.,PetersenG.,DavisS.,ForsterJ.Breastfeedingprotectsagainstacutegastroenteritisduetorotavirusininfants.EurJPediatr.2010Dec;169(12):1471-6.
KunzC.,RudloffS.,BaierW.,KleinN.,StrobelS.Oligosaccharidesinhumanmilk:structural,functional,andmetabolicaspects.AnnuRevNutr.2000;20:699-722. HesterS.N.,ChenX.,LiM.,MonacoM.H.,ComstockS.S.,KuhlenschmidtT.B.,KuhlenschmidtM.S.,DonovanS.M.Humanmilkoligosaccharidesinhibitrotavirus
infectivityinvitroandinacutelyinfectedpiglets.BrJNutr.2013Oct;110(7):1233-42. ComstockS.S.,WangM.,HesterS.N.,LiM.,DonovanS.M.Selecthumanmilkoligosaccharidesdirectlymodulateperipheralbloodmononuclearcellsisolated
from10-d-oldpigs.BrJNutr.2014Mar14;111(5):819-28. ComstockS.S.,LiM.,WangM.,MonacoM.H.,KuhlenschmidtT.B.,KuhlenschmidtM.S.,DonovanS.M.Dietaryhumanmilkoligosaccharidesbutnotprebiotic
oligosaccharidesincreasecirculatingnaturalkillercellandmesentericlymphnodememoryTcellpopulationsinnoninfectedandrotavirus-infectedneonatalpiglets.JNutr.2017Jun;147(6):1041-1047.
LiM.,MonacoM.H.,WangM.,ComstockS.S.,KuhlenschmidtT.B.,FaheyG.C.Jr,MillerM.J.,KuhlenschmidtM.S.,DonovanS.M.Humanmilkoligosaccharidesshortenrotavirus-induceddiarrheaandmodulatepigletmucosalimmunityandcolonicmicrobiota.ISMEJ.2014Aug;8(8):1609-20.
ContributedbyDr.SandeepRavindranFreelanceScienceWriterSandeepr.com
HolderPasteurizationHasLimitedImpactontheNutrientsinHumanMilk• Holderpasteurizationisthestandardtreatmentforhumanmilkdonatedtomilkbanksacrosstheworld.• TheevidencesuggeststhatHolderpasteurizationreducestheamountsofseveralvitaminsinmilk,andmayalterthe
digestibilityofcertainproteins.• AlthoughthecarbohydrateconcentrationsinhumanmilkappearunaffectedbyHolderpasteurizationandfreezer
storage,somestudiessuggestthatfatsareslightlydecreased,andmaybeevenmoresoiftheysticktotheplasticequipmentthatisoftenusedtofeedyounginfants.
Holderpasteurization,orHoP,isusedtheworldovertohelpensurethatthemilkdistributedbyhumanmilkbanksissafeforinfantstoconsume.Thankstoitsbroadeffectivenessatdestroyingalonglistofbacteriaandviruses—includingHIVandEbola—HoPis
recommendedbytheWorldHealthOrganizationandtheAmericanAcademyofPediatrics.Butdoesraisingthetemperatureofhumanmilkto62.5°Cforhalfanhourbreakdownanyofitsconstituentssuchthatthenutritionalcontentofmilkisaffected?Thissecondarticleinafive-partseriesaboutHoPfindsthattheevidenceonthistopicisrelativelythin:differentmethodsofevaluatingthecompositionofmilkhavefrequentlyledtodifferentconclusions.Overall,however,eventhoughsomestudiesindicatethatseveralvitamins,iron,fats,andcertainproteinscanbealteredbyHoP,researchersrarelyconsiderthenutritionalchangestobeclinicallyrelevant.ThereareseveralmicronutrientsforwhichevidenceofachangeresultingfromHoPisunequivocal.VitaminC,forexample,hasrepeatedlybeenshowntobedestroyedbyHoP,whereasvitaminsAandEarethoughttobebetterretained[1].Butthedataarelessclearforsomeothervitamins.Forexample,severalstudiesshowHoP-inducedreductionsintheBvitamins,whileothersdonot[1].
Lastyear,FabioGomesoftheUniversityofQueensland,inBrisbane,Australia,andhiscolleagues,usedliquidchromatographyandmassspectrometrytoanalyzetheconcentrationsofvitaminDcompoundsinhumanmilkbeforeandafterpasteurization[2].TheyfoundthatvariousvitaminDcompoundswereaffected—vitaminD2,D3,25(OH)D2and25(OH)D3—withlossesduetopasteurizationinthe10%—20%range.Whetherthiscouldhaveanyimpactoninfanthealthislittleunderstood:whilevitaminD’simportanceintheregulationcalciumandphosphateabsorptionintheintestinesiswellestablished,thevitaminDrequirementsofpre-terminfants,whooftenreceivemilk-bankmilk,arenot.SomeofthosesameBrisbane-basedscientistsalsocontributedlastyeartoapaperabouttheimpactofHoPonthemineralcontentofmilk[3].Againusingmassspectrometry,theyfoundnoevidenceforalterationsintheamountofthetraceelementszinc,copper,selenium,manganese,iodine,molybdenum,andbromine.Theironcontentofmilkdiddecreaseby6.5%afterHoP—astatisticallysignificantshift—butthislossisnotthoughttobeproblematicforprematureinfants.AuthorsNorMohd-Taufekandhercolleaguesdonotrecommendmilksupplementationwithironasamatterofcourse.Sugarsinmilkappeartoholdupwelltoheattreatmentandstorage.Thisistheconclusionofarecentreviewthatevaluatedtheevidencearoundchangesintheamountsoflactoseandglucose—aswellasglycanssuchasglycosaminoglycansandoligosaccharides[1].Thesummary
of44papers,whichallmeasuredchangesinhumanmilk’scompositionbeforeandafterpasteurization,waswrittenbytheUniversityofTurin’sChiaraPeila,andateamthatisspreadamongvariousItalianinstitutions.Theconcentrationsofthevastmajorityofthecarbohydratesinvestigateddidnotchange.Whenitcametoglucose,however,differentstudieshavefounditsconcentrationstoincrease,todecreaseandtoremainconstantafterHoP.Fatsinmilkstoremuchoftheenergythatpowersinfantwriggling,smilingandcrying.Crucially,theyalsohelpprematureinfantsputonweight.Henceanyreductioninthefatcontentofdonormilkcouldhaveimportantconsequencesforchoicesaroundmilksupplementation.(Asitis,motherswhodonatemilkhavegenerallybeenlactatingforawhile,andasaresult,producemilkwithalowerenergycontentthannewermothers[4].)TwostudieshaveaddressedthequestionofwhetherHoPaltershumanmilk’sfatcontent,withonebyLeyetal.[5],whichreliedonbombcalorimetry,reportingnochange,andanotherbyGarcía-Laraetal.[6]notingadecrease.García-Lara’steamusedinfraredspectrometrytoanalyze34samplesofdonatedmilkfrom28donorstotheHospital12deOctubreinMadrid,Spain.Theyreportthatpasteurizationfollowedbyfreezerstoragefor180daysresultedin6.2%decreaseinfatanda5%decreaseintheenergycontentofmilk,respectively.Ofthe6.2%decrease,3.5%wastheresultfromHoP,andtheremainder(2.7%)wasduetostorage.Theargumentthattheprocessoffreezingandthawingmightinfluencepasteurizedhumanmilk’sfatcontentisalsobackedupbyworkbyAlanAraujoVieiraandhiscolleaguesattheFernandesFigueiraInstitute,inRiodeJaneiro,Brazil[4].Theyreporta5.5%reductioninhumanmilk’sfatcontentfollowingpasteurizationandahugefurtherreductionof56.6%asaresultofcontinuousinfusiondelivery(oneofthetwomainwaysofdeliveringmilktoinfantswhocannotsuck).Vieiraandhiscolleaguessuggesttheexplanationforsuchalargedropmightberuptureoffatglobulemembranesthatcouldfacilitatefatsstickingtothewallsoftheplasticequipmentandsyringesthatarecommonlyusedtofeedveryyounginfants.ResearchintotheimpactofHoPontheproteinsinmilktendstofocusonchangesintheproteins’levelsofactivity,suchasintheimmunologicalfunctionsofsomeproteins,ratherthanontheamountofproteinavailableasanutrient.Therearegoodreasonsforthis,whichwillbeexploredinnextmonth’sissueofSPLASH!®.Perhapsthemostin-depthstudyonthetopic,however,combinesthesetwoconcerns.Inthissense,CristinaBaroatCNR’sInstituteoftheScienceofFoodProduction,inTurin,Italy,andherteam,notethatthedigestibility(andthusthenutritionalsupply)oftheproteinsinhumanmilkcanbereducedwhensomeaminoacidsundergocarbonylation[7].SotheyapproachedthequestionofthehowmuchnutritionallyavailableproteinispresentbeforeandafterHoPbyimmunostainingtheproteincomponentofhumanmilkwithacompoundthatbindstocarbonylgroups.Whentheycomparedthecarbonylationofoneofthemostimportantproteinsinmilk,β-casein,beforeandafterHoP,theyfounditlittlechanged(butcaseins
weresomewhatdegradedbytheheattreatment).Anotherimportantprotein,lactoferrin,didshowconsiderabledifference,however.Becauselactoferrinbindsiron,itscarbonylationduringHoPmayexplainthesmallreductioninhumanmilk’sironcontentthatMohd-Taufekandhercolleaguesreportedlastyear[3].Lactoferrinismuchmorethanabuildingblocktobecutupbygutenzymesandreconstitutedintheformofinfantmuscle.Itcanitselffightgermsandisthoughttoevenstimulateinfantintestinaldevelopment.Checkbacknextmonthtolearnmoreabouthowthis,andotherbiologicallyactiveproteinsinhumanmilk,areaffectedbyHoP.
PeilaC.,MoroG.E.,BertinoE.,CavallarinL.,GiribaldiM.,GiulianiF.,CresiF.&CosciaA.2016.Theeffectofholderpasteurizationonnutrientsandbiologically-activecomponentsindonorhumanmilk:areview.Nutrients.8,477.doi:10.3390/nu8080477
GomesF.,ShawP.N.,WhitfieldK.,KoortsP.,McConachyH.&HewavitharanaaA.K.2016.EffectofpasteurisationontheconcentrationsofvitaminDcompoundsindonorbreastmilk.InternationalJournalofFoodSciencesandNutrition.67(1):16–19.
Mohd-TaufekN.,CartwrightD.,DaviesM.,HewavitharanaA.K.,KoortsP.,McConachyH.,ShawP.N.,SumnerR.&WhitfieldK.2016.Theeffectofpasteurizationontraceelementsindonorbreastmilk.JournalofPerinatology.36,897–900.
VieiraA.A.,MendesSoaresF.V.,PortoPimentaH.,AbranchesA.D.,&LopesMoreiraM.E.2011.Analysisoftheinfluenceofpasteurization,freezing/thawing,andofferprocessesonhumanmilk’smacronutrientconcentrations.EarlyHumanDevelopment.87:577–580.
LeyS.H.,HanleyA.J.,StoneD.,&O’ConnorD.L.2011.Effectsofpasteurizationonadiponectinandinsulinconcentrationsindonorhumanmilk.PediatricResearch.70:278–281.
García-LaraN.R.,EscuderViecoD.,DelaCruz-BértoloJ.,Lora-PablosD.,UretaVelascoN.&Pallás-AlonsoC.R.2013.Effectofholderpasteurizationandfrozenstorageonmacronutrientsandenergycontentofbreastmilk.JournalofPediatricGastroenterologyandNutrition.57(3):377-382.
BaroC.,GiribaldiM.,ArslanogluS.,GiuffridaM.G.,DellavalleG.,ContiA.,TonettoP.,BiasiniA.,CosciaA.,FabrisC.,MoroG.E.,CavallarinL.&BertinoE.2011.Effectoftwopasteurizationmethodsontheproteincontentofhumanmilk.FrontiersinBioscience.E3,818-829.
ContributedbyAnnaPetherickProfessionalsciencewriter&editorwww.annapetherick.comHumanMilkOligosaccharidesCanDirectlyInhibitStreptococcusGrowth
• Anewstudyfindsthathumanmilkoligosaccharides(HMOs)candirectlyinhibitthegrowthofgroupBStreptococcus(GBS).
• GBSgrowthisinhibitedbycertainneutral,non-sialylatedformsofHMOs,andappearstobemediatedbyaGBS-specificglycosyltransferase.
• TheneutralHMOsactsynergisticallywithcommonantibiotics,andtheresultssuggestthatHMOscouldpotentiallybeusedasdirectantimicrobialtherapies.
Sugarsfoundinhumanmilk,calledhumanmilkoligosaccharides(HMOs),havevariousprotectiveeffectsagainstinfectiousagents[1,2].HMOsareknowntopreventtheattachmentofmicrobialpathogenstothehost[3-5].Theyalsohaveotherprotectiveeffectsagainstinfectionsbyactingonthehostimmunesystem[6,7].Inanewstudy,ProfessorLarsBodeoftheUCSanDiegoSchoolofMedicineandtheLarsson-RosenquistFoundationMother-Milk-InfantCenterofResearchExcellencefoundthatHMOscandirectlyinhibitthegrowthofgroupBStreptococcus(GBS)[8].“Thisisyetagainacompletelynewdirectiontothestory.TheHMOsareactingnotbyservingasanti-adhesives,notbyhavinganeffectonthehost,butbydirectlydoingsomethingtothepathogen,”saysBode.Theresultsofthisstudyfurtheraddtoourunderstandingoftheantimicrobialbenefitsofhumanmilk.“Thenumberonelessonisthathumanmilkisaverypowerfultoolforfightinginfections,andyetanotherreasontoempowerwomentobreastfeediftheycan,”saysBode.
BodeandAnnLin,thefirstauthorofthecurrentstudy,hadpreviouslyshownthatHMOsregulatethehostinnateimmuneresponseinordertopreventuropathogenicEscherichiacoli(UPEC)invasionintobladderepithelialcells[9].“Theoligosaccharidesreprogramepithelialcellsandhaveaprotectiveeffectonthehostthatmakesthehostsaferagainstthepathogen,”saysBode.Butinthatstudy,HMOsdidnothaveanydirecteffectonbacterialgrowth.Afterthatstudy,LindecidedtolookattheeffectsofHMOsonvariousotherpathogens.Sheobtainedseveraldifferentpathogensfromco-authorandcollaboratorProfessorVictorNizet.“ShesprinkledHMOsonavarietyofpathogens,andallofasuddenfoundthatgroupBStreptococcuswouldjustnotgrowanymore,”saysBode.“Eveninthecompleteabsenceofhostcells,theHMOshadadirecteffectonthepathogen,”hesays.“Thiswascompletelynew,”saysBode.
TheHMOsinhibitedthegrowthofGBS,butdidnotkillthepathogenevenathighconcentrations.TheydidnotinhibitthegrowthofUPEC,Pseudomonasaeruginosa,ormethicillin-resistantStaphylococcusaureus.
Fortheirinitialexperiments,theresearchersusedHMOsisolatedfrompooledhumanmilk.“Wealwaysstartoutwitholigosaccharidesisolatedfrompooleddonormilkfromdifferentmoms,aseverymommakesslightlydifferentoligosaccharides,”saysBode.TheresearchersthensetouttoidentifythespecificHMOsinvolvedininhibitingGBSgrowth.“Wehaveabout150to200differentoligosaccharides,sothequestionis,whichoneisresponsible?”TheresearchersusedmultidimensionalchromatographytoseparatethepooledHMOsintovariousfractions,andfoundthattheinhibitionofGBSgrowthwasrestrictedtoafractionofnon-sialylated,neutralHMOs.Interestingly,thisisincontrasttothegroup’spreviousfindings,whereitwassialylatedHMOsthatinfluencedhostinnateimmunedefenseagainstUPEC.“Wehave150to200oligosaccharides,andifitwasthesametwoorthreethatwereresponsibleforalltheseeffects,wewouldn’tneedsomany,”saysBode.“Atthispointit’smoreofacoincidenceifwefindthesameoligosaccharidedoingthingsoverandover,”hesays.BasedontheiranalysisoftheneutralHMOfraction,theresearchersselectedninecommerciallyavailableoligosaccharidestotest.TheresearchersfoundthatGBSgrowthwasinhibitedbylacto-N-tetraose(LNT)andlacto-N-fucopentaoseI(LNFPI).Interestingly,astructuralisomerofLNTcalledlacto-N-neotetraosedidnotsignificantlyinhibitGBSgrowth.“Whatreallysurpriseduswasthatlacto-N-neotetraosedoesn’twork,”saysBode.“Averytinychange,justalittlebitofthestructureattachedslightlydifferentlyseemstomakeabigdifference,”hesays.ToelucidatethemechanismsbywhichtheHMOsmightbeinhibitingGBSgrowth,theresearchersthenscreenedalibraryofGBSmutantsthattheyobtainedfromco-authorProfessorKellyDoran.“Oneofthemutantsdidn’trespondtotheoligosaccharides,itgrewjustaswellwithandwithoutoligosaccharides,”saysBode.“ThatgaveustheideathattheproteinencodedbythemutatedgenecouldbeapotentialtargetfortheeffectoftheHMOs,”hesays.Throughbioinformaticanalysis,theresearchersidentifiedthemutatedgeneasaputativeglycosyltransferase,andconfirmedthroughdirectedmutationsthatthisgenewasresponsibleforthesusceptibilityofGBStoneutralHMOs.“OurthinkingisthatthisglycosyltransferasetakescomponentsoftheHMOsandincorporatesthemintothecellwallstructuresthatthencannolongerbeelongatedandwon’tallowthebacteriatogrow,”saysBode.Theresearchersarecurrentlyworkingonlabelingindividualoligosaccharidestoseewhichgetsincorporatedinthecellwall.ThisparticularglycosyltransferasealsoappearstobeuniquetoGBS,whichcouldexplainwhyHMOsdidnotinhibitgrowthintheotherbacteriatested.“Ifbacteriadon’trelyonthisglycosyltransferase,thentheywon’tputHMOsinthecellwall,andcancontinuetogrow,”saysBode.BodeandhiscolleaguesalsofoundthattheneutralHMOsactedsynergisticallywithcommonantibiotics,aspriorexposuretoHMOsdramaticallyreducedtheinhibitorydoseofvancomycinandciprofloxacin.“Thatwasprobablythecoolestpartofthestory,tofindsynergisticeffects,”saysBode.“Giventhecrisisofantibioticresistance,itcouldcertainlyhelptobeabletousealowerantibioticdoseinthepresenceofHMOs,”hesays.HMOscouldalsohaveadditionaltherapeuticutilitybesidesbeingusedinconjunctionwithexistingantibiotics.“I’mthinkingaheadtobeingabletodeveloptheseasnoveldrugs,”saysBode.“Theywouldbeaveryattractiveadditiontoourarsenalofantimicrobials,”hesays.“WewouldexpectHMOstopassrelativelyeasilythroughregulatoryrequirements,sincewefeedthemtobabiesnaturallyallthetime,”saysBode.“Itwouldbeagreatapplicationofanaturalcompound,”hesays.There’sstillsomewaystogobeforeresearchersconfirmwhetherHMOscouldhavetherapeuticpotentialagainstGBSinhumans.“It’sgreattoseethisinatesttube,butweeventuallywanttoseeifthiseffecttranslatesinhumans,especiallynowthatwe’restartingtogetFDAGRAS-approvedHMOs,”saysBode[“GRAS”isanacronymforGenerallyRecognizedAsSafe,anFDAdesignationreferringtoasubstanceorchemicaladdedtofoodthatisconsideredbyqualifiedexpertstobesafeundertheconditionsofitsintendeduse].“There’sstillalotofworktobedone,butit’sveryexciting,it’sagreatfieldtobein,”hesays.
KunzC.,RudloffS.,BaierW.,KleinN.,StrobelS.Oligosaccharidesinhumanmilk:structural,functional,andmetabolicaspects.AnnuRevNutr.200020:699-722. BodeL.,Jantscher-KrennE.Structure-functionrelationshipsofhumanmilkoligosaccharides.AdvNutr.2012May1;3(3):383S-91S. Martín-SosaS.,MartínM.J.,HuesoP.Thesialylatedfractionofmilkoligosaccharidesispartiallyresponsibleforbindingtoenterotoxigenicand
uropathogenicEscherichia colihumanstrains.JNutr.2002Oct;132(10):3067-72. NewburgD.S.Innateimmunityandhumanmilk.JNutr.2005May;135(5):1308-12. Jantscher-KrennE.,LauwaetT.,BlissL.A.,ReedS.L.,GillinF.D.,BodeL.HumanmilkoligosaccharidesreduceEntamoeba histolyticaattachmentand
cytotoxicityinvitro.BrJNutr.2012Nov28;108(10):1839-46. HeY.,LiuS.,KlingD.E.,LeoneS.,LawlorN.T.,HuangY.,FeinbergS.B.,HillD.R.,NewburgD.S.Thehumanmilkoligosaccharide2ʹ-fucosyllactosemodulatesCD14
expressioninhumanenterocytes,therebyattenuatingLPS-inducedinflammation.Gut.2016Jan;65(1):33-46. LiM.,MonacoM.H.,WangM.,ComstockS.S.,KuhlenschmidtT.B.,FaheyG.C.Jr.,MillerM.J.,KuhlenschmidtM.S.,DonovanS.M.Humanmilkoligosaccharides
shortenrotavirus-induceddiarrheaandmodulatepigletmucosalimmunityandcolonicmicrobiota.ISMEJ.2014Aug;8(8):1609-20. LinA.E.,AutranC.A.,SzyszkaA.,EscajadilloT.,HuangM.,GodulaK.,PruddenA.R.,BoonsG.J.,LewisA.L.,DoranK.S.,NizetV.,BodeL.Humanmilk
oligosaccharidesinhibitgrowthofgroupBStreptococcus.JBiolChem.2017Jul7;292(27):11243-11249. LinA.E.,AutranC.A.,EspanolaS.D.,BodeL.,NizetV.HumanmilkoligosaccharidesprotectbladderepithelialcellsagainsturopathogenicEscherichia
coliinvasionandcytotoxicity.JInfectDis.2014Feb1;209(3):389-98.
ContributedbyDr.SandeepRavindran
FreelanceScienceWriterSandeepr.comEditorialStaffofSPLASH!milkscienceupdate:Dr.DanielleLemay,ExecutiveEditorDr.KatieRodger,ManagingEditorAnnaPetherick,AssociateEditorProf.KatieHinde,ContributingEditorDr.LaurenMilliganNewmark,AssociateEditorDr.RossTellam,AssociateEditorDr.SandeepRavindran,AssociateEditorProf.PeterWilliamson,AssociateEditorCoraMorgan,EditorialAssistantTasslynGester,CopyEditor
FundingprovidedbyCaliforniaDairyResearchFoundationandtheInternationalMilkGenomicsConsortium
TheviewsandopinionsexpressedinthisnewsletterarethoseofthecontributingauthorsandeditorsanddonotnecessarilyrepresenttheviewsoftheiremployersorIMGCsponsors.
