Philippa Kaur

Research Group for Genomic Epidemiology, Technical University of Denmark, Kgs, Lyngby, DenmarkPatrick Munk, Christian Brinch, Frederik Duus Møller, Thomas N. Petersen, Rene S. Hendriksen, Anne Mette Seyfarth, Jette S. Kjeldgaard, Christina Aaby Svendsen & Frank M. AarestrupCentre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh, UKBram van Bunnik & Mark WoolhouseCentre for Antibiotic Resistance Research (CARe), University of Gothenburg, Gothenburg, SwedenFanny Berglund & D. G. Joakim LarssonDepartment of Viroscience, Erasmus MC, Rotterdam, The NetherlandsMarion KoopmansInstitute of Public Health, Tirana, AlbaniaArtan BegoUniversidad de Buenos Aires, Buenos Aires, ArgentinaPablo PowerMelbourne Water Corporation, Melbourne, AustraliaCatherine Rees & Kris CoventryCharles Darwin University, Darwin, AustraliaDionisia LambrinidisUniversity of Copenhagen, Frederiksberg C, DenmarkElizabeth Heather Jakobsen Neilson & Yaovi Mahuton Gildas HounmanouCharles Darwin University, Darwin Northern Territory, AustraliaKaren GibbCanberra Hospital, Canberra, AustraliaPeter CollignonALS Water, Scoresby, AustraliaSusan CassarAustrian Agency for Health and Food Safety (AGES), Vienna, AustriaFranz AllerbergerUniversity of Dhaka, Dhaka, BangladeshAnowara Begum & Zenat Zebin HossainEnvironmental Protection Department, Bridgetown, St. Michael, BarbadosCarlon WorrellLaboratoire Hospitalier Universitaire de Bruxelles (LHUB-ULB), Brussels, BelgiumOlivier VandenbergAQUAFIN NV, Aartselaar, BelgiumIlse PietersPolytechnic School of Abomey-Calavi, Abomey-Calavi, BeninDougnon Tamègnon VictorienUniversidad Catσlica Boliviana San Pablo, La Paz, BoliviaAngela Daniela Salazar Gutierrez & Freddy SoriaPublic Health Institute of the Republic of Srpska, Faculty of Medicine University of Banja Luka, Banja Luka, Bosnia and HerzegovinaVesna Rudić GrujićPublic Health Institute of the Republic of Srpska, Banja Luka, Bosnia and HerzegovinaNataša MazalicaBotswana International University of Science and Technology, Palapye, BotswanaTeddie O. RahubeUniversidade Federal de Minas Gerais, Belo Horizonte, BrazilCarlos Alberto Tagliati & Larissa Camila Ribeiro de SouzaOswaldo Cruz Institute, Rio de Janeiro, BrazilDalia RodriguesVale Institute of Technology, Belιm, PA, BrazilGuilherme OliveiraNational Center of Infectious and Parasitic Diseases, Sofia, BulgariaIvan IvanovUniversity of Ouagadougou, Ouagadougou, Burkina FasoBonkoungou Isidore Juste & Traoré OumarInstitut Pasteur du Cambodge, Phnom Penh, CambodiaThet Sopheak & Yith VuthyCentre Pasteur du Cameroun, Yaoundι, CameroonAntoinette Ngandjio, Ariane Nzouankeu & Ziem A. Abah Jacques OlivierUniversity of Regina, Regina, CanadaChristopher K. YostEau Terre Environnement Research Centre (INRS-ETE), Quebec City G1K 9A9, Canada and Indian Institute of Technology, Jammu, IndiaPratik KumarEau Terre Environnement Research Centre (INRS-ETE), Quebec City G1K 9A9, Canada and Lassonde School of Enginerring, York University, Toronto, CanadaSatinder Kaur BrarUniversity of N’Djamena, N’Djamena, ChadDjim-Adjim TaboEscuela de Medicina Veterinaria, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago, ChileAiko D. AdellInstitute of Public Health, Santiago, ChileEsteban Paredes-Osses & Maria Cristina MartinezUniversidad Catolica del Maule, Centro de Biotecnología de los Recursos Naturales, Facultad de Ciencias Agrarias y Forestales, Talca, ChileSara Cuadros-OrellanaGuangdong Provincial Center for Disease Control and Prevention, Guangzhou, ChinaChangwen Ke, Huanying Zheng & Li BaishengThe Hong Kong Polytechnic University, Hong Kong, ChinaLok Ting Lau & Teresa ChungShantou University Medical College, Shantou, ChinaXiaoyang JiaoNanjing University of Information Science and Technology, Nanjing, ChinaYongjie YuCenter for Disease Control and Prevention of Henan province, Zhengzhou, ChinaZhao JiaYongColombian Integrated Program for Antimicrobial Resistance Surveillance – Coipars, CI Tibaitatα, Corporaciσn Colombiana de Investigaciσn Agropecuaria (AGROSAVIA), Tibaitatα – Mosquera, Cundinamarca, ColombiaJohan F. Bernal Morales, Maria Fernanda Valencia & Pilar Donado-GodoyInstitut Pasteur de Côte d’Ivoire, Abidjan, Côte d’IvoireKalpy Julien CoulibalyUniversity of Zagreb, Zagreb, CroatiaJasna HrenovicAndrija Stampar Teaching Institute of Public Health, Zagreb, CroatiaMatijana JergovićVeterinary Research Institute, Brno, Czech RepublicRenáta KarpíškováCentre de Recherche en Sciences Naturelles de Lwiro (CRSN-LWIRO), Bukavu, Democratic Republic of CongoZozo Nyarukweba DeogratiasBIOFOS A/S, Copenhagen K, DenmarkBodil ElsborgTechnical University of Denmark, Kgs., Lyngby, DenmarkLisbeth Truelstrup Hansen & Pernille Erland JensenSuez Canal University, Ismailia, EgyptMohamed AbouelnagaUniversity of Sadat City, Sadat City, EgyptMohamed Fathy SalemMinistry of Health, Environmental Microbiology, Tallinn, EstoniaMarliin KoolmeisterAddis Ababa University, Addis Ababa, EthiopiaMengistu Legesse & Tadesse EgualeUniversity of Helsinki, Helsinki, FinlandAnnamari HeikinheimoFrench Institute Search Pour L’exploitation De La Mer (Ifremer), Nantes, FranceSoizick Le Guyader & Julien SchaefferInstituto Nacional de Investigaciσn en Salud Pϊblica-INSPI (CRNRAM), Galαpagos, Quito, EcuadorJose Eduardo VillacisNational Public Health Laboratories, Ministry of Health and Social Welfare, Kotu, GambiaBakary SannehNational Center for Disease Control and Public Health, Tbilisi, GeorgiaLile MalaniaRobert Koch Institute, Berlin, GermanyAndreas Nitsche & Annika BrinkmannTechnische Universitδt Dresden, Institute of Hydrobiology, Dresden, GermanySara Schubert, Sina Hesse & Thomas U. BerendonkUniversity for Development Studies, Tamale, GhanaCourage Kosi Setsoafia SabaUniversity of Ghana, Accra, GhanaJibril MohammedKwame Nkrumah University of Science and Technology, Kumasi, PMB, GhanaPatrick Kwame FegloCouncil for Scientific and Industrial Research Water Research Institute, Accra, GhanaRegina Ama BanuVeterinary Research Institute of Thessaloniki, Hellenic Agricultural Organisation-DEMETER, Thermi, GreeceCharalampos KotzamanidisAthens Water Supply and Sewerage Company (EYDAP S.A.), Athens, GreeceEfthymios LytrasUniversidad de San Carlos de Guatemala, Guatemala City, GuatemalaSergio A. LickesSemmelweis University, Institute of Medical Microbiology, Budapest, HungaryBela KocsisUniversity of Veterinary Medicine, Budapest, HungaryNorbert SolymosiUniversity of Iceland, Reykjavνk, IcelandThorunn R. ThorsteinsdottirCochin University of Science and Technology, Cochin, IndiaAbdulla Mohamed HathaKasturba Medical College, Manipal, IndiaMamatha BallalApollo Diagnostics, Mangalore, IndiaSohan Rodney BangeraShiraz University of Medical Sciences, Shiraz, IranFereshteh FaniShahid Beheshti University of Medical Sciences, Tehran, IranMasoud AlebouyehNational University of Ireland Galway, Galway, IrelandDearbhaile Morris, Louise O’Connor & Martin CormicanBen Gurion University of the Negev and Ministry of Health, Beer-Sheva, IsraelJacob Moran-GiladIstituto Zooprofilattico Sperimentale del Lazio e della Toscana, Rome, ItalyAntonio Battisti, Elena Lavinia Diaconu & Patricia AlbaCNR – Water Research Institute, Verbania, ItalyGianluca Corno & Andrea Di CesareNational Institute of Infectious Diseases, Tokyo, JapanJunzo Hisatsune, Liansheng Yu, Makoto Kuroda, Motoyuki Sugai & Shizuo KayamaNational Center of Expertise, Taldykorgan, KazakhstanZeinegul ShakenovaMount Kenya University, Thika, KenyaCiira KiiyukiaKenya Medical Research Institute, Nairobi, KenyaEric Ng’enoUniversity of Prishtina “Hasan Prishtina” & National Institute of Public Health of Kosovo, Pristina, KosovoLul RakaKuwait Institute for Scientific Research, Kuwait City, KuwaitKazi Jamil, Saja Adel Fakhraldeen & Tareq AlaatiInstitute of Food Safety, Riga, LatviaAivars Bērziņš, Jeļena Avsejenko, Kristina Kokina, Madara Streikisa & Vadims BartkevicsAmerican University of Beirut, Beirut, LebanonGhassan M. MatarCentral Michigan University & Michigan Health Clinics, Saginaw, MI, USAZiad DaoudNational Food and Veterinary Risk Assessment Institute, Vilnius, LithuaniaAsta Pereckienė & Ceslova Butrimaite-AmbrozevicieneLuxembourg Institute of Science and Technology, Belvaux, LuxembourgChristian PennyInstitut Pasteur de Madagascar, Antananarivo, MadagascarAlexandra Bastaraud & Jean-Marc CollardUniversity of Antananarivo, Centre d’Infectiologie Charles Mιrieux, Antananarivo, MadagascarTiavina Rasolofoarison, Luc Hervé Samison & Mala Rakoto AndrianariveloUniversity of Malawi, Blantyre, MalawiDaniel Lawadi BandaMalaysian Genomics Resource Centre Berhad, Kuala Lumpur, MalaysiaArshana AminAIMST University, COMBio, Kedah, MalaysiaHeraa Rajandas & Sivachandran ParimannanWater Services Corporation, Luqa, MaltaDavid SpiteriEnvironmental Health Directorate, St. Venera, MaltaMalcolm Vella HaberUniversity of Mauritius, Reduit, MauritiusSunita J. SantchurnInstitute for Public Health Montenegro, Podgorica, MontenegroAleksandar Vujacic & Dijana DjurovicInstitut Pasteur du Maroc, Casablanca, MoroccoBrahim Bouchrif & Bouchra KarraouanCentro de Investigaηγo em Saϊde de Manhiηa (CISM), Maputo, MozambiqueDelfino Carlos VubilAgriculture and Forestry University, Kathmandu, NepalPushkar PalNational Institute for Public, Health and the Environment (RIVM), Bilthoven, The NetherlandsHeike Schmitt & Mark van PasselUniversity of Otago, Dunedin, New ZealandGert-Jan Jeunen & Neil GemmellUniversity of Otago, Christchurch, New ZealandStephen T. ChambersUniversity of Central America, Managua, NicaraguaFania Perez Mendoza & Jorge Huete-PιrezUniversidad Nacional Autσnoma de Nicaragua-Leσn, Leσn, NicaraguaSamuel VilchezUniversity of Ilorin, Ilorin, NigeriaAkeem Olayiwola Ahmed, Ibrahim Raufu Adisa & Ismail Ayoade OdetokunUniversity of Ibadan, Ibadan, NigeriaKayode FashaeNorwegian Institute of Public Health, Oslo, NorwayAnne-Marie Sørgaard & Astrid Louise WesterVEAS, Slemmestad, NorwayPia Ryrfors & Rune HolmstadUniversity of Agriculture, Faisalabad, PakistanMashkoor MohsinAga Khan University, Karachi, PakistanRumina Hasan & Sadia ShakoorLaboratorio Central de Salud Publica, Asuncion, ParaguayNatalie Weiler Gustafson & Claudia Huber SchillInstituto Nacional de Salud, Lima, PeruMaria Luz Zamudio RojasUniversidad de Piura, Piura, PeruJorge Echevarria Velasquez & Felipe Campos YauceWHO Environmental and Occupational Health, Manila, PhilippinesBonifacio B. MagtibayMaynilad Water Services, Inc., Quezon City, PhilippinesKris Catangcatang & Ruby SibuloNational Veterinary Research Institute, Pulawy, PolandDariusz WasylUniversidade Catσlica Portuguesa, CBQF – Centro de Biotecnologia e Quνmica Fina – Laboratσrio Associado, Escola Superior de Biotecnologia, Porto, PortugalCelia Manaia & Jaqueline RochaAguas do Tejo Atlantico, Lisboa, PortugalJose Martins & Pedro ÁlvaroGwangju Institute of Science and Technology, Gwangju, Republic of KoreaDoris Di Yoong Wen, Hanseob Shin & Hor-Gil HurKorea Advanced Institute of Science and Technology, Daejeon, Republic of KoreaSukhwan YoonInstitute of Public Health of the Republic of North Macedonia, Skopje, Republic of North MacedoniaGolubinka Bosevska & Mihail KochubovskiState Medical and Pharmaceutical University, Chișinău, Republic of MoldovaRadu CojocaruNational Agency for Public Health, Chișinău, Republic of MoldovaOlga BurduniucKing Abdullah University of Science and Technology, Thuwal, Saudi ArabiaPei-Ying HongUniversity of Edinburgh, Edinburgh, Scotland, UKMeghan Rose PerryInstitut Pasteur de Dakar, Dakar, SenegalAmy GassamaInstitute of Veterinary Medicine of Serbia, Belgrade, SerbiaVladimir RadosavljevicNanyang Technological University, Singapore, SingaporeMoon Y. F. Tay, Rogelio Zuniga-Montanez & Stefan WuertzPublic Health Authority of the Slovak Republic, Bratislava, SlovakiaDagmar Gavačová, Katarína Pastuchová & Peter TruskaNational Laboratory of Health, Environment and Food, Ljubljana, SloveniaMarija TrkovIndependent consultant, Johannesburg, South AfricaKaren KeddyDaspoort Waste Water Treatment Works, Pretoria, South AfricaKerneels EsterhuyseKorea Advanced Institute of Science and Technology, Daejeon, South KoreaMin Joon SongSchool of Veterinary Sciences, Lugo, SpainMarcos Quintela-BalujaLabaqua, Santiago de Compostela, SpainMariano Gomez LopezIRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la Universitat Autonoma de Barcelona, Bellaterra, SpainMarta Cerdà-CuéllarUniversity of Kelaniya, Ragama, Sri LankaR. R. D. P. Perera, N. K. B. K. R. G. W. Bandara & H. I. PremasiriMedical Research Institute, Colombo, Sri LankaSujatha PathirageCaribbean Public Health Agency, Catries, Saint LuciaKareem CharlemagneThe Sahlgrenska Academy at the University of Gothenburg, Gothenburg, SwedenCarolin RutgerssonSwedish University of Agricultural Sciences, Uppsala, SwedenLeif Norrgren & Stefan ÖrnFederal Food Safety and Veterinary Office (FSVO), Bern, SwitzerlandRenate BossAra Region Bern AG, Herrenschwanden, SwitzerlandTanja Van der HeijdenCenters for Disease Control, Taipei, TaiwanYu-Ping HongKilimanjaro Clinical Research Institute, Moshi, TanzaniaHappiness Houka KumburuSokoine University of Agriculture, Morogoro, TanzaniaRobinson Hammerthon MdegelaFaculty of Science and Technology, Suratthani Rajabhat University, Surat Thani, ThailandKaknokrat ChonsinFaculty of Public Health, Mahidol University, Bangkok, ThailandOrasa SuthienkulFaculty of Medicine Siriraj Hospital, Bangkok, ThailandVisanu ThamlikitkulNational Institute for Public Health and the Environment (RIVM), Bilthoven, NetherlandsAna Maria de Roda HusmanNational Institute of Hygiene, Lomι, TogoBawimodom BidjadaAgence de Mιdecine Prιventive, Dapaong, TogoBerthe-Marie Njanpop-LafourcadeDivision of Integrated Surveillance of Health Emergencies and Response, Lomι, TogoSomtinda Christelle Nikiema-PessinabaPublic Health Institution of Turkey, Ankara, TurkeyBelkis LeventHatay Mustafa Kemal University, Hatay, TurkeyCemil KurekciMakerere University, Kampala, UgandaFrancis Ejobi & John Bosco KaluleAbu Dhabi Public Health Center, Abu Dhai, United Arab EmiratesJens ThomsenDubai municipality, WWTP Al Aweer, Dubai, UAEOuidiane ObaidiRashid Hospital, Dubai, UAELaila Mohamed JassimNorthumbrian Water, Northumbria House, Abbey Road, Pity Me, Durham, UKAndrew MooreUniversity of Exeter Medical School, Cornwall, UKAnne Leonard, Lihong Zhang & William H. GazeNewcastle University, Newcastle upon Tyne, UKDavid W. Graham & Joshua T. BunceBrightwater Treatment Plant, Woodinville, WA, USABrett LeforDepartment of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, USADrew Capone & Joe BrownUniversity of North Carolina, Chapel Hill, USAEmanuele Sozzi & Mark D. SobseyUniversity of Washington, Seattle, WA, USAJohn Scott Meschke, Nicola Koren Beck, Pardi Sukapanpatharam & Phuong TruongBaylor University, Waco, USAMichael DavisColumbia Boulevard WWTP, Portland, USARonald LilienthalEastern Illinois University, Charleston, USASanghoon KangThe Ohio State University, Columbus Ohio, USAThomas E. WittumLaboratorio Tecnolσgico del Uruguay, Montevideo, UruguayNatalia Rigamonti & Patricia BaklayanInstitute of Public Health in Ho Chi Minh City, Ho Chi Minh, VietnamChinh Dang Van, Doan Minh Nguyen Tran & Nguyen Do PhucUniversity of Zambia, Lusaka, ZambiaGeoffrey Kwenda More

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ParticipantsIn total, 80, 63, and 56 participants in the EM, CM, and control groups, respectively, initially agreed to participate in this study. Nevertheless, 28, 12, and 13 individuals in the EM, CM, and control groups, respectively, withdrew their participation and did not bring any fecal samples to the study site. After providing fecal samples, 10 and 6 individuals with EM and CM, respectively, reported intake of probiotics and were excluded from the analysis. No participant in the control group consumed probiotics during the study period. Eventually, 42, 45, and 43 participants in the EM, CM, and control groups, respectively, were enrolled (Fig. 1). The demographic and clinical characteristics of participants are summarized in Table 1. All participants with EM and CM used acute treatments for migraine. Moreover, 25 (59.5%) and 27 (60.0%) participants with EM and CM, respectively, received prophylactic treatment for migraine. Of the 42 participants with EM, 20 used anti-epileptic medications, 11 used beta blockers, 2 used an anti-depressant, and 1 used a calcium-channel blocker for prophylactic treatment. Of the 45 participants with CM, 23 used anti-epileptic medications, 8 used beta blockers, 1 used an anti-depressant, and no participant used calcium-channel blockers for prophylactic treatment. No participant in the EM, CM, and control groups was infected with SARS-CoV-2 before or during participation in the study.Figure 1Flow of participants in a study on the composition of gut microbiota in participants with episodic or chronic migraine.Full size imageTable 1 Demographic and clinical characteristics of participants with episodic and chronic migraine and the control.Full size tableCollection of 16 s RNA sequencing dataWe obtained 7,802,425 read sequences, accounting for 99.8% of the valid sequences from the fecal samples of 130 participants. According to barcode and primer sequence filtering, an average of 59,305 (range, 3716–90,832) observed sequences per sample was recovered for downstream analysis. Thus, 2,242,325 sequences were obtained from the controls for phylogenetic analysis, whereas 2,747,952 and 2,812,148 sequences were obtained from the EM and CM groups, respectively.Microbial diversityAlpha diversity was defined as microbial community richness and evenness. Alpha diversities in the genus richness, as evaluated by Chao1 (Fig. 2A), Shannon (Fig. 2B), and Simpson (Fig. 2C) indices, did not differ significantly among the EM, CM, and control groups. Beta diversity represented the community composition dissimilarity between samples. PCoA with the weighted UniFrac distance (Fig. 3A and Supplementary Fig. S1A, p = 0.176, permutational multivariate analysis of variance [PERMANOVA]), the unweighted UniFrac distance (Fig. 3B and Supplementary Fig. S1B, p = 0.132, PERMANOVA), and the Bray–Curtis dissimilarity index (Fig. 3C and Supplementary Fig. S1C, p = 0.220, PERMANOVA) for beta diversity at the genus level among the EM, CM, and control groups revealed that these three groups could not be separated.Figure 2Alpha diversity at the genus level using Chao1 (A), Shannon (B), and Simpson (C) indices*,†. *Controls (green) and participants with episodic migraine (blue) and chronic migraine (yellow). †In the box plots, the lower boundary of the box indicates the 25th percentile; a blue line within the box marks the median, and the upper boundary of the box indicates the 75th percentile. Whiskers above (red) and below the box (green) indicate the highest and the lowest values, respectively.Full size imageFigure 3Beta diversity of microbiota in principal coordinate analysis plot with the weighted UniFrac distance (A), the unweighted UniFrac distance (B) and the Bray–Curtis dissimilarity index (C)*. *Controls (green) and participants with episodic migraine (blue) and chronic migraine (yellow).Full size imageRelative abundance of fecal microbes between participants with EM and the controlRelative abundance of fecal microbes at the phylum level did not differ significantly among participants in the control, EM, and CM groups (Supplementary Fig. S2). Moreover, Tissierellales (p = 0.001) and Tissierellia (p = 0.001) were more abundant in the EM group than that in the control group at the order and class levels, respectively (Fig. 4A). At the family level, Peptoniphilaceae (p = 0.001) and Eubacteriaceae (p = 0.045) occurred at a significantly higher proportion in the EM group than that in the control group. Furthermore, at the genus level, the abundance of 11 genera differed significantly between the two groups, including one more abundant and 10 less abundant genera in the EM group. Catenibacterium (p = 0.031) and Olsenella (p = 0.038) had the highest relative abundance in the control and EM groups, respectively.Figure 4Taxonomic differences in fecal microbiota among participants. The fold change (log2) denotes the difference in relative abundance between participants with episodic migraine and the control (A), between those with chronic migraine and the control (B), and between those with episodic and chronic migraine (C). CM chronic migraine; EM episodic migraine.Full size imageRelative abundance of fecal microbes between participants with CM and the controlThe analysis results at the class, order, family, genus, and species levels between CM and control groups are illustrated in Fig. 4B. Tissierellia (p = 0.001), Tissierellales (p = 0.001), and Peptoniphilaceae (p = 0.001) were more abundant in the CM group than that in the control group at the class, order, and family levels, respectively; however, at the genus level, the abundances of 18 genera differed significantly, including four more abundant and 14 less abundant genera in the CM group than in the control group.Relative abundance of fecal microbes between participants with EM and CMThe analysis results at the class, order, family, and genus levels between CM and EM groups are summarized in Fig. 4C. At the class level, Bacilli (p = 0.033) were less abundant in the CM group than that in the EM group; however, at the order level, Selenomonadales (p = 0.016) and Lactobacillales (p = 0.034) were less abundant in the CM group than that in the EM group. Moreover, at the class level, Selenomonadaceae (p = 0.016) and Prevotellaceae (p = 0.012) were less abundant in the CM group than that in the EM group. Furthermore, at the genus level, PAC001212_g (p = 0.019) revealed relative positive predominancy in the CM groups, whereas Prevotella (p = 0.019), Holdemanella (p = 0.009), Olsenella (p = 0.033), Adlercreutzia (p = 0.018), and Coprococcus (p = 0.040) revealed relative positive predominancy in the EM group.Association among fecal microbiota and clinical characteristics and comorbidities of migraineAmong the five genera (Roseburia, Eubacterium_g4, Agathobacter, PAC000195_g, and Catenibacterium) depicting predominance or less-predominance both in EM and CM groups, we conducted additional analyses for clinical characteristics and migraine comorbidities.Combining the results of the 42 and 45 participants with EM and CM, respectively, the Poisson regression analysis for relative abundance of microbiota revealed that a higher composition of PAC000195_g (p = 0.040) was significantly associated with lower headache frequency (Table 2). Furthermore, Agathobacter (p = 0.009) had a negative association with severe headache intensity (Table 3). Anxiety was associated with Catenibacterium (p = 0.027); however, depression did not reveal any association with the five genera (Table 3).Table 2 The association between headache frequency and the relative abundance of microbiota.*Full size tableTable 3 The association of severe headache intensity and comorbidities with the relative abundance of microbiota*.Full size tableRelative abundance of fecal microbes in participants with EM based on prophylactic treatmentAlpha and beta diversities in participants with EM did not differ significantly based on their prophylactic treatment (Supplementary Figs S3A–C, S4A–C, and S5A–C). At the genus level, Klebsiella (p = 0.009), Enterobacteriaceae_g (p = 0.006), and Faecalibacterium (p = 0.046) were more abundant in the prophylactic group than the non-prophylactic group (Supplementary Fig. S6A).Relative abundance of fecal microbes in participants with CM based on prophylactic treatmentAlpha and beta diversities in participants with CM did not differ significantly based on prophylactic treatment (Supplementary Figs S7A–C, S8A–C, and S9A–C). Emergencia (p = 0.043), Ruthenibacterium (p = 0.005), Eggerthella (p = 0.003), PAC000743_g (p = 0.034), and Anaerostipes (p = 0.039) were more abundant in the prophylactic group, whereas PAC000196_g (p = 0.049), Fusicatenibacter (p = 0.028), and Faecalibacterium (p = 0.021) were more abundant in the non-prophylactic group at the genus level (Supplementary Fig. S6B). More

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