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Nutritional Neurosciences Amit Kumar Tripathi Malini Kotak Editors Gut Microbiome in Neurological Health and Disorders Nutritional Neurosciences SeriesEditor MohamedEssa,SultanQaboosUniversity,Qaboos,Oman This book series aims to publish volumes focusing on both basic and clinical researchinthefieldofnutritionalneurosciencewithafocusondelineatingtheeffect of nutrition on brain function and behavior. The books will examine the role of different nutrients, food agents and supplements (both macro and micro) on brain health,neurodevelopment,neurochemistry,andbehaviour.Thebookswillexamine the influence of diet, including phytochemicals, antioxidants, dietary supplements, food additives, and other nutrients on the physiology and metabolism of neurons, neurotransmittersandtheirreceptors,cognition,behavior,andhormonalregulations. Thebookswillalsocover theinfluenceofnutrients anddietarysupplements on the management of neurological disorders. It details the mechanism of action of phytonutrientsonsignalingpathwayslinkedwithproteinfolding,aggregation,and neuroinflammation. The books published in the series will be useful for neurosci- entists, nutritionists, neurologists, psychiatrists, and those interested in preventive medicine. (cid:129) Amit Kumar Tripathi Malini Kotak Editors Gut Microbiome in Neurological Health and Disorders Editors AmitKumarTripathi MaliniKotak ClinicalResearchDivision,Schoolof PersonalCareDivision–HealthandHygiene BasicandAppliedScience ITCLifeSciencesandTechnologyCentre GalgotiasUniversity Bangalore,Karnataka,India GreaterNoida,UttarPradesh,India ISSN2730-6712 ISSN2730-6720 (electronic) NutritionalNeurosciences ISBN978-981-19-4529-8 ISBN978-981-19-4530-4 (eBook) https://doi.org/10.1007/978-981-19-4530-4 ©TheEditor(s)(ifapplicable)andTheAuthor(s),underexclusivelicensetoSpringerNatureSingapore PteLtd.2022 Thisworkissubjecttocopyright.AllrightsaresolelyandexclusivelylicensedbythePublisher,whether thewholeorpartofthematerialisconcerned,specificallytherightsoftranslation,reprinting,reuseof illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similarordissimilarmethodologynowknownorhereafterdeveloped. Theuseofgeneraldescriptivenames,registerednames,trademarks,servicemarks,etc.inthispublication doesnotimply,evenintheabsenceofaspecificstatement,thatsuchnamesareexemptfromtherelevant protectivelawsandregulationsandthereforefreeforgeneraluse. The publisher, the authors, and the editorsare safeto assume that the adviceand informationin this bookarebelievedtobetrueandaccurateatthedateofpublication.Neitherthepublishernortheauthorsor theeditorsgiveawarranty,expressedorimplied,withrespecttothematerialcontainedhereinorforany errorsoromissionsthatmayhavebeenmade.Thepublisherremainsneutralwithregardtojurisdictional claimsinpublishedmapsandinstitutionalaffiliations. ThisSpringerimprintispublishedbytheregisteredcompanySpringerNatureSingaporePteLtd. The registered company address is: 152 Beach Road, #21-01/04 Gateway East, Singapore 189721, Singapore Preface In 2006, neuroscientist Jane Foster and her team were working with two groups ofmice:onewithahealthygutmicrobiome,andtheotherthatlackedamicrobiome. They observed that the mice without gut bacteria seemed less anxious than their healthyequivalents.Whenthesemicewereplacedinamazewithsomeopenpaths andsomewalled-inones,theypreferredtheexposedpaths.Theyconcludedthatthe gut bacteria influence the brain and behaviour of these mice. When she tried to publishthisfinding,itwasrejectedmultipletimesaspeoplethoughtthatthiswasan artefact.Eventually,after3yearsand7submissions,herfindingswerepublished. In recent years, however, the gut-brain axis has been established and numerous publicationsoverthepastdecadehaverevealedthatthegutmicrobiomecouldhave profound effects on the brain and might be involved in neurological disorders. Animal and preliminary human studies suggest that microbiome can trigger or alter the course of neurological conditions like Parkinson’s disease and Autism. Several therapies that modulate the gut microbiome have been reported to have shownpromisingresultsandfewofthesetherapiesarealreadybeingtestedinhuman clinicaltrials. The interaction between the gastrointestinal tract (GIT), gut microbiome, and centralnervoussystem(CNS)iscomplexandbidirectional,forexample,ahealthy gutenvironmentwithdiversemicroorganismsensuresnormalfunctioningofbrain, whereastheCNSmodulatesmostaspectsofGITfunctioningandphysiology.Asa result, theterm microbiota-gut-brainaxis (MGBA) wascoined tostress theimpor- tance of these interactions. The interactions between MGBA occur by means of neural, endocrine, immune, and humoral links. This book provides an overview of bidirectional communication between gut-microbiome-brain, various pathways, nutrients, metabolites, etc. involved in MGBA interactions, relevance of this axis incontextofneurologicaldisordersandpotentialtherapeuticinterventions,involv- inggutmicrobiomeorpro/pre-biotic,whichcanameliorateneurologicaldisorders. Briefly,wehaveintroducedmicrobiota-gut-brainaxis,itsinteractionwithimmu- nity and various metabolites. We have also discussed neurological disorders with focusonneurodegenerativediseasesandcerebrovasculardiseases.Wealsoprovide v vi Preface anoverviewofpotentialmicrobiome-basedtherapeuticsinterventionsforneurolog- ical disorders. Lastly,consideringthat microbiomeisan evolving subjectandwith an aim of continuous education process of students and researchers, this book provides a detailed understanding of methodologies which can be instrumental in studyingmicrobiome.Thetextreflectsthecurrentstateofevidenceavailableinthe field of gut microbiome in context of neural health and disease and presents some novelfindingsincludingreportsonSARS-CoV-2andCOVID-19. GreaterNoida,India AmitKumarTripathi Bangalore,India MaliniKotak Contents 1 GutMicrobiomeBrainAxis:AnIntroduction. . . . . . . . . . . . . . . . . 1 SantoshAnand,SunilKumarMishra,andJayamSamlin 2 CrossTalkBetweenGutMicrobiotaandHostImmuneCells. . . . . 7 AnkitVerma,AwakashSoni,andPriyaGupta 3 Microbiota–Gut–BrainAxisandNeurodegenerativeDisorder. . . . 27 AwakashSoni,AnkitVerma,andPriyaGupta 4 GutMicrobiotaRegulationofCerebralStroke. . . . . . . . . . . . . . . . 47 KaushlendraKumar,HemaKumari,andAmitKumarTripathi 5 Aging:ImpactofGutMicrobiota. . . . . . . . . . . . . . . . . . . . . . . . . . 71 SantoshAnand,RanojiRaoNarasingaRaoLakshmikanth, KannasandraRamaiahManjula, DoddhakathanahalliRamanathJayashree,andTekupalliRavikiran 6 GutMicrobiomeRegulationofAppetiteandRole inNeurologicalDisorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 AnkitaSingh,OmPrakashVerma,andRajavashisthTripathi 7 HumanDiets,GutMicrobiome,andNeuroinflammation. . . . . . . . 107 JyotiSingh,ZoyaKhan,andTripathiRajavashisth 8 DietaryFattyAcids,GutMicrobiome,andGut–Brain Communication:ACurrentPerspective. . . . . . . . . . . . . . . . . . . . . 121 SantoshAnand,S.K.Sukrutha,B.R.Shilpa,andA.Nagarathna 9 RoleofShort-ChainFattyAcidsfromGutMicrobiotain NeuroendocrinePathogenesisManagement. . . . . . . . . . . . . . . . . . . 139 NehaSahu,PrabhatUpadhyay,andSunilKumarMishra vii viii Contents 10 PotentialRoleofProbioticsonGutMicrobiotainNeurological Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153 JovelVargheseJoseandS.Aliya 11 ReversalofMetabolicDisorderThroughtheRestoration ofGutMicrobiota. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179 PrabhatUpadhyay,DiyaKalra,SarikaGupta, andSunilKumarMishra 12 GutMicrobiomeandDiet:PromisingApproachforTreatment ofCognitiveImpairment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195 AwakashSoni,PriyaGupta,andAnkitVerma 13 Nanoplastics,GutMicrobiota,andNeurodegeneration. . . . . . . . . . 211 AnanyaRai 14 GutMicrobiome,COVID-19,andNeurologicalImpairment. . . . . . 235 RichaDas,RiyaSingh,andAmitKumarTripathi 15 ToolstoStudyGutMicrobiome. . . . . . . . . . . . . . . . . . . . . . . . . . . 253 K.S.Sreevatshan,VeenaG.Nair,C.S.Srinandan,andGaneshBabu MalliMohan 16 Germ-freeMiceTechnology:OpportunityforFutureResearch. . . 271 AshishJainandAnandMaurya 17 GutMicrobiomeandNeurodegeneration:ABioinformatics Approach. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 297 SwetanshuandPratichiSingh About the Editors Amit Kumar Tripathi isworking asAssistantProfessor, Clinical Research Divi- sion, School of Basic and Applied Science, Galgotias University, Greater Noida, India.Hehasdonehis Doctoral Research atCSIR-CentralDrugResearchInstitute and was awarded by Jamia Hamdard, New Delhi. His doctoral and post-doctoral researchwasfocusedonthemolecularmechanismtounderstandcerebralstrokeand cancer. He has several years of research experience on animal models of various neurologicaldisorders.Hehaspublishedhisresearchworkinvariouspeer-reviewed international journals, books, and chapters. He is involved in teaching various coursessuchasRecombinantDNATechnology,Nanotechnology,MolecularTher- apeutics, Microbial Technology, Animal Biotechnology, Yellow Biotechnology at Bachelor,andMasterofScienceinSchoolofBasicandAppliedScience,Galgotias University. He has been awarded several national and international awards for his contributiontoresearchinhealthanddisease. MaliniKotak isanAssociateScientistintheHealthandHygienesegmentatITC Ltd., India’s leading fast moving consumer goods company. During her doctoral training at the University of Texas at Arlington and post-doctoral training at ITC Ltd.,shehasextensivelyworkedongut,hand,skin,andvaginalmicrobiomeandits association with human health and disease. She has more than 10 years of work experienceinindustryandacademiaandhasdonecutting-edgeresearchinfieldslike biotherapeutics, microbiome, precision medicine, genomics, and cancer biology. Shehaspublishedseveralresearchpapersinreputedjournals,bookchapter,andis arecipientofseveralresearchfellowshipsinIndiaandabroad.Hercurrentresearch involves the development of novel products which are of relevance in health and hygieneindustry. ix