Little is known about how zoonotic virus infections manifest in wildlife reservoirs. However, a common health consequence of enteric virus infections is gastrointestinal diseases following a shift in gut microbial composition. The sub-Saharan hipposiderid bat complex has recently emerged to host at least three coronaviruses (CoVs), with Hipposideros caffer D appearing particularly susceptible to Hibecovirus CoV-2B infection. In this study, we complement body condition and infection status data with information about the gut microbial community to understand the health impact of CoV infections in a wild bat population. Of the three CoVs, only infections with the distantly SARS-related Hibecovirus CoV-2B were associated with lower body condition and altered the gut microbial diversity and composition. The gut microbial community of infected bats became progressively less diverse and more dissimilar with infection intensity, arguing for dysbiosis as per the Anna Karenina principle. Putatively beneficial bacteria, such as Alistipes and Christensenella, decreased with infection intensity, while potentially pathogenic bacteria, namely Mycoplasma and Staphylococcus, increased. Infections with enterically replicating viruses may therefore cause changes in body condition and gut dysbiosis with potential negative health consequences even in virus reservoirs. We argue that high-resolution data on multiple health markers, ideally including microbiome information, will provide a more nuanced picture of bat disease ecology.

Department of Wildlife and Range Management Kwame Nkrumah University of Science and Technology AK 385 1973 Kumasi Ghana

German Centre for Infection Research and Charité Universitätsmedizin Berlin Institute of Virology Berlin 10117 Germany

Institute of Evolutionary Ecology and Conservation Genomics Ulm University Ulm BW 89081 Germany

Institute of Vertebrate Biology Czech Academy of Sciences Brno 675 02 Czech Republic

School of Natural Sciences Macquarie University Sydney New South Wales 2113 Australia

School of Science Engineering and the Environment Salford University Salford M5 4NT UK

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Le Chatelier  E, Nielsen  T, Qin  J  et al.  Richness of human gut microbiome correlates with metabolic markers. Nature  2013;500:541–6. 10.1038/nature12506 PubMed DOI

Sommer  F, Anderson  JM, Bharti  R  et al.  The resilience of the intestinal microbiota influences health and disease. Nat Rev Microbiol  2017;15:630–8. PubMed

Trevelline  BK, Fontaine  SS, Hartup  BK  et al.  Conservation biology needs a microbial renaissance: a call for the consideration of host-associated microbiota in wildlife management practices. Proc R Soc B Biol Sci  2019;286:20182448. PubMed PMC

Härer  A, Thompson  KA, Schluter  D  et al.  Associations between gut microbiota diversity and a host fitness proxy in a naturalistic experiment using Threespine stickleback fish. Mol Ecol  2024;33:e17571. 10.1111/mec.17571 PubMed DOI PMC

Risely  A, Müller-Klein  N, Schmid  DW  et al.  Climate change drives loss of bacterial gut mutualists at the expense of host survival in wild meerkats. Glob Chang Biol  2023;29:5816–28. PubMed

Worsley  SF, Davies  CS, Mannarelli  M-E  et al.  Gut microbiome composition, not alpha diversity, is associated with survival in a natural vertebrate population. Animal Microbiome  2021;3:84. PubMed PMC

Zaneveld  JR, McMinds  R, Vega  TR. Stress and stability: applying the Anna Karenina principle to animal microbiomes. Nat Microbiol  2017;2:17121. PubMed

Baldini  F, Hertel  J, Sandt  E  et al.  Parkinson’s disease-associated alterations of the gut microbiome predict disease-relevant changes in metabolic functions. BMC Biol  2020;18:62. PubMed PMC

Brestoff  JR, Artis  D. Commensal bacteria at the interface of host metabolism and the immune system. Nat Immunol  2013;14:676–84. PubMed PMC

Rooks  MG, Veiga  P, Wardwell-Scott  LH  et al.  Gut microbiome composition and function in experimental colitis during active disease and treatment-induced remission. The ISME Journal  2014;8:1403–17. PubMed PMC

Barbian  HJ, Li  Y, Ramirez  M  et al.  Destabilization of the gut microbiome marks the end-stage of simian immunodeficiency virus infection in wild chimpanzees. American J Primatol  2018;80:e22515. PubMed PMC

McKenna  P, Hoffmann  C, Minkah  N  et al.  The macaque gut microbiome in health, Lentiviral infection, and chronic Enterocolitis. PLoS Pathog  2008;4:e20. PubMed PMC

Wilmes  P, Martin-Gallausiaux  C, Ostaszewski  M  et al.  The gut microbiome molecular complex in human health and disease. Cell Host Microbe  2022;30:1201–6. PubMed

Ganz  HH, Doroud  L, Firl  AJ  et al.  Community-level differences in the microbiome of healthy wild mallards and those infected by influenza a viruses. mSystems  2017;2:e00188–16. 10.1128/msystems.00188-16 PubMed DOI PMC

Moeller  AH, Shilts  M, Li  Y  et al.  SIV-induced instability of the chimpanzee gut microbiome. Cell Host Microbe  2013;14:340–5. PubMed PMC

Wasimuddin  CVM, Ganzhorn  JU, Rakotondranary  J  et al.  Adenovirus infection is associated with altered gut microbial communities in a non-human primate. Sci Rep  2019;9:13410. PubMed PMC

Williams  CE, Hammer  TJ, Williams  CL. Diversity alone does not reliably indicate the healthiness of an animal microbiome. The ISME Journal  2024;18:wrae133. PubMed PMC

Brook  CE, Dobson  AP. Bats as ‘special’ reservoirs for emerging zoonotic pathogens. Trends Microbiol  2015;23:172–80. PubMed PMC

Edson  D, Peel  AJ, Huth  L  et al.  Time of year, age class and body condition predict Hendra virus infection in Australian black flying foxes (Pteropus alecto). Epidemiol Infect  2019;147:e240. PubMed PMC

Letko  M, Seifert  SN, Olival  KJ  et al.  Bat-borne virus diversity, spillover and emergence. Nat Rev Microbiol  2020;18:461–71. PubMed PMC

Li  W, Shi  Z, Yu  M  et al.  Bats are natural reservoirs of SARS-like coronaviruses. Science  2005;310:676–9. PubMed

Mollentze  N, Streicker  DG. Viral zoonotic risk is homogenous among taxonomic orders of mammalian and avian reservoir hosts. Proc Natl Acad Sci USA  2020;117:9423–30. PubMed PMC

Wacharapluesadee  S, Duengkae  P, Chaiyes  A  et al.  Longitudinal study of age-specific pattern of coronavirus infection in Lyle’s flying fox (Pteropus lylei) in Thailand. Virol J  2018;15:38. PubMed PMC

McMichael  L, Edson  D, Mayer  D  et al.  Temporal variation in physiological biomarkers in black flying-foxes (Pteropus alecto). Australia Ecohealth  2016;13:49–59. PubMed PMC

Moreno  KR, Weinberg  M, Harten  L  et al.  Sick bats stay home alone: fruit bats practice social distancing when faced with an immunological challenge. Ann N Y Acad Sci  2021;1505:178–90. PubMed PMC

Sánchez  CA, Phelps  KL, Frank  HK  et al.  Advances in understanding bat infection dynamics across biological scales. Proc R Soc B Biol Sci  2024;291:20232823. PubMed PMC

Ruhs  EC, McFerrin  K, Jones  DN  et al.  Rapid GIT transit time in volant vertebrates, with implications for convergence in microbiome composition. bioRxiv [Preprint]. 2024:2024.08.09.607319. 10.1101/2024.08.09.607319 DOI

Klite  PD. Intestinal bacterial Flora and Transit time of three Neotropical bat species. J Bacteriol  1965;90:375–9. PubMed PMC

Lutz  HL, Jackson  EW, Webala  PW  et al.  Ecology and host identity outweigh evolutionary history in shaping the bat microbiome. mSystems  2019;4:e00511–9. PubMed PMC

Song  SJ, Sanders  JG, Delsuc  F  et al.  Comparative analyses of vertebrate gut microbiomes reveal convergence between birds and bats. MBio  2020;11:e02901–19. PubMed PMC

Jones  DN, Ravelomanantsoa  NAF, Yeoman  CJ  et al.  Do gastrointestinal microbiomes play a role in bats’ unique viral hosting capacity?  Trends Microbiol  2022;30:632–42. PubMed PMC

Williams  CE, Fontaine  SS. Commentary: the microbial dependence continuum: towards a comparative physiology approach to understand host reliance on microbes. Comp Biochem Physiol A Mol Integr Physiol  2024;296:111690. PubMed

Price  ER, Brun  A, Caviedes-Vidal  E  et al.  Digestive adaptations of aerial lifestyles. Physiology  2015;30:69–78. PubMed

Daniel  DS, Ng  YK, Chua  EL  et al.  Isolation and identification of gastrointestinal microbiota from the short-nosed fruit bat Cynopterus brachyotis brachyotis. Microbiol Res  2013;168:485–96. PubMed

Ingala  MR, Simmons  NB, Dunbar  M  et al.  You are more than what you eat: potentially adaptive enrichment of microbiome functions across bat dietary niches. anim microbiome  2021;3:82. PubMed PMC

Phillips  CD, Hanson  J, Wilkinson  JE  et al.  Microbiome structural and functional interactions across host dietary niche space. Integr Comp Biol  2017;57:743–55. PubMed

Prem Anand  AA, Sripathi  K. Digestion of cellulose and xylan by symbiotic bacteria in the intestine of the Indian flying fox (Pteropus giganteus). Comp Biochem Physiol A Mol Integr Physiol  2004;139:65–9. PubMed

Zepeda Mendoza  ML, Xiong  Z, Escalera-Zamudio  M  et al.  Hologenomic adaptations underlying the evolution of sanguivory in the common vampire bat. Nat Ecol Evol  2018;2:659–68. PubMed PMC

Berman  TS, Weinberg  M, Moreno  KR  et al.  In sickness and in health: the dynamics of the fruit bat gut microbiota under a bacterial antigen challenge and its association with the immune response. Front Immunol  2023;14:1152107. PubMed PMC

Liu  B, Chen  X, Zhou  L  et al.  The gut microbiota of bats confers tolerance to influenza virus (H1N1) infection in mice. Transbound Emerg Dis  2022;69:e1469–87. PubMed

Wasimuddin  BSD, Tschapka  M, Page  R  et al.  Astrovirus infections induce age-dependent dysbiosis in gut microbiomes of bats. ISME J  2018;12:2883–93. PubMed PMC

Anthony  SJ, Johnson  CK, Greig  DJ  et al.  Global patterns in coronavirus diversity. Virus Evolution  2017;3:vex012. PubMed PMC

Corman  VM, Baldwin  HJ, Tateno  AF  et al.  Evidence for an ancestral Association of Human Coronavirus 229E with bats. J Virol  2015;89:11858–70. PubMed PMC

Aljabr  W, Alruwaili  M, Penrice-Randal  R  et al.  Amplicon and metagenomic analysis of Middle East respiratory syndrome (MERS) coronavirus and the microbiome in patients with severe MERS. mSphere  2021;6. 10.1128/msphere.00219-21 PubMed DOI PMC

Sencio  V, Machelart  A, Robil  C  et al.  Alteration of the gut microbiota following SARS-CoV-2 infection correlates with disease severity in hamsters. Gut Microbes  2022;14:2018900. PubMed PMC

Sokol  H, Contreras  V, Maisonnasse  P  et al.  SARS-CoV-2 infection in nonhuman primates alters the composition and functional activity of the gut microbiota. Gut Microbes  2021;13:1893113. PubMed PMC

Zuo  T, Liu  Q, Zhang  F  et al.  Depicting SARS-CoV-2 faecal viral activity in association with gut microbiota composition in patients with COVID-19. Gut  2021;70:276–84. PubMed PMC

Essex  M, Millet Pascual-Leone  B, Löber  U  et al.  Gut microbiota dysbiosis is associated with altered tryptophan metabolism and dysregulated inflammatory response in COVID-19. npj Biofilms Microbiomes  2024;10:1–15. PubMed PMC

Drexler  JF, Corman  VM, Drosten  C. Ecology, evolution and classification of bat coronaviruses in the aftermath of SARS. Antivir Res  2014;101:45–56. PubMed PMC

Vallo  P, Guillén-Servent  A, Benda  P  et al.  Variation of mitochondrial DNA in the Hipposideros caffer complex (Chiroptera: Hipposideridae) and its taxonomic implications. Acta  2008;10:193–206.

Meyer  M, Melville  DW, Baldwin  HJ  et al.  Bat species assemblage predicts coronavirus prevalence. Nat Commun  2024;15:2887. PubMed PMC

Pfefferle  S, Oppong  S, Drexler  JF  et al.  Distant relatives of severe acute respiratory syndrome coronavirus and close relatives of human coronavirus 229E in bats. Ghana Emerg Infect Dis  2009;15:1377–84. PubMed PMC

Schmid  DW, Meyer  M, Wilhelm  K  et al.  MHC class II genes mediate susceptibility and resistance to coronavirus infections in bats. Mol Ecol  2023;32:3989–4002. PubMed

Sánchez  CA, Becker  DJ, Teitelbaum  CS  et al.  On the relationship between body condition and parasite infection in wildlife: a review and meta-analysis. Ecol Lett  2018;21:1869–84. PubMed

Drexler  JF, Corman  VM, Müller  MA  et al.  Bats host major mammalian paramyxoviruses. Nat Commun  2012;3:796. PubMed PMC

Annan  A, Baldwin  HJ, Corman  VM  et al.  Human Betacoronavirus 2c EMC/2012–related viruses in bats, Ghana and Europe. Emerg Infect Dis  2013;19:456–9. PubMed PMC

Drexler  JF, Kupfer  B, Petersen  N  et al.  A novel diagnostic target in the hepatitis C virus genome. PLoS Med  2009;6:e1000031. PubMed PMC

Schmid  DW, Fackelmann  G, Wasimuddin  RJ  et al.  A framework for testing the impact of co-infections on host gut microbiomes. anim microbiome  2022;4:48. PubMed PMC

Caporaso  JG, Lauber  CL, Walters  WA  et al.  Global patterns of 16S rRNA diversity at a depth of millions of sequences per sample. Proc Natl Acad Sci  2011;108:4516–22. PubMed PMC

Bolyen  E, Rideout  JR, Dillon  MR  et al.  Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nat Biotechnol  2019;37:852–7. PubMed PMC

Callahan  BJ, McMurdie  PJ, Rosen  MJ  et al.  DADA2: high-resolution sample inference from Illumina amplicon data. Nat Methods  2016;13:581–3. PubMed PMC

Quast  C, Pruesse  E, Yilmaz  P  et al.  The SILVA ribosomal RNA gene database project: improved data processing and web-based tools. Nucleic Acids Res  2012;41:D590–6. PubMed PMC

Katoh  K, Standley  DM. MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol Biol Evol  2013;30:772–80. PubMed PMC

Price  MN, Dehal  PS, Arkin  AP. FastTree 2 – approximately maximum-likelihood trees for large alignments. PLoS One  2010;5:e9490. PubMed PMC

Huson  DH, Scornavacca  C. Dendroscope 3: an interactive tool for rooted phylogenetic trees and networks. Syst Biol  2012;61:1061–7. PubMed

R Core Team . R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, 2022.

McMurdie  PJ, Holmes  S. Phyloseq: an R package for reproducible interactive analysis and graphics of microbiome census data. PLoS One  2013;8:e61217. PubMed PMC

Davis  NM, Proctor  DM, Holmes  SP  et al.  Simple statistical identification and removal of contaminant sequences in marker-gene and metagenomics data. Microbiome  2018;6:226. PubMed PMC

Oksanen  J, Simpson  GL, Blanchet  FG  et al.  Vegan: Community Ecology Package, 2022.

Kuznetsova  A, Brockhoff  PB, Christensen  RHB. lmerTest package: tests in linear mixed effects models. J Stat Softw  2017;82:1–26.

McGuire  LP, Kelly  LA, Baloun  DE  et al.  Common condition indices are no more effective than body mass for estimating fat stores in insectivorous bats. J Mammal  2018;99:1065–71.

Kembel  SW, Cowan  PD, Helmus  MR  et al.  Picante: R tools for integrating phylogenies and ecology. Bioinformatics  2010;26:1463–4. PubMed

Schloss  PD. Waste not, want not: revisiting the analysis that called into question the practice of rarefaction. mSphere  2023;9:e00355–23. PubMed PMC

Weiss  S, Xu  ZZ, Peddada  S  et al.  Normalization and microbial differential abundance strategies depend upon data characteristics. Microbiome  2017;5:27. PubMed PMC

Niku  J, Hui  FKC, Taskinen  S  et al.  Gllvm: fast analysis of multivariate abundance data with generalized linear latent variable models in r. Methods Ecol Evol  2019;10:2173–82.

Johnson  JS, Spakowicz  DJ, Hong  B-Y  et al.  Evaluation of 16S rRNA gene sequencing for species and strain-level microbiome analysis. Nat Commun  2019;10:5029. PubMed PMC

Schloss  PD, Jenior  ML, Koumpouras  CC  et al.  Sequencing 16S rRNA gene fragments using the PacBio SMRT DNA sequencing system. PeerJ  2016;4:e1869. PubMed PMC

Risely  A. Applying the core microbiome to understand host–microbe systems. J Anim Ecol  2020;89:1549–58. PubMed

Quinn  TP, Erb  I, Gloor  G  et al.  A field guide for the compositional analysis of any-omics data. GigaScience  2019;8:giz107. PubMed PMC

Wood  S. Generalized Additive Models: An Introduction with R, Second Edition (2nd ed.) edn. Chapman and Hall/CRC, 2017.

Coretta  S, van Rij  J, Wieling  M. Tidy Model Visualisation for Generalized Additive Models, 2021.

Irving  AT, Ahn  M, Goh  G  et al.  Lessons from the host defences of bats, a unique viral reservoir. Nature  2021;589:363–70. PubMed

Ruiz-Aravena  M, McKee  C, Gamble  A  et al.  Ecology, evolution and spillover of coronaviruses from bats. Nat Rev Microbiol  2022;20:299–314. PubMed PMC

Joffrin  L, Hoarau  AOG, Lagadec  E  et al.  Seasonality of coronavirus shedding in tropical bats. R Soc Open Sci  2022;9:211600. PubMed PMC

Seltmann  A, Corman  VM, Rasche  A  et al.  Seasonal fluctuations of Astrovirus, but not coronavirus shedding in bats inhabiting human-modified tropical forests. EcoHealth  2017;14:272–84. PubMed PMC

Taylor  PJ, Monadjem  A, Nicolaas  SJ. Seasonal patterns of habitat use by insectivorous bats in a subtropical African agro-ecosystem dominated by macadamia orchards. Afr J Ecol  2013;51:552–61.

Inoue  T, Nakayama  J, Moriya  K  et al.  Gut Dysbiosis associated with hepatitis C virus infection. Clin Infect Dis  2018;67:869–77. PubMed

Dai  W, Leng  H, Li  J  et al.  The role of host traits and geography in shaping the gut microbiome of insectivorous bats. mSphere  2024;9:e00087–24. PubMed PMC

Zuo  T, Zhang  F, Lui  GCY  et al.  Alterations in gut microbiota of patients with COVID-19 during time of hospitalization. Gastroenterology  2020;159:944–955.e8. PubMed PMC

Sumithra  TG, Chaturvedi  VK, Susan  C  et al.  Mycoplasmosis in wildlife: a review. Eur J Wildl Res  2013;59:769–81.

Fleischer  R, Schmid  DW, Wasimuddin  BSD  et al.  Interaction between MHC diversity and constitution, gut microbiota and Astrovirus infections in a neotropical bat. Mol Ecol  2022;31:3342–59. PubMed

Eby  P, Peel  AJ, Hoegh  A  et al.  Pathogen spillover driven by rapid changes in bat ecology. Nature  2023;613:340–4. PubMed PMC

Crowley  DE, Falvo  CA, Benson  E  et al.  Bats generate lower affinity but higher diversity antibody responses than those of mice, but pathogen-binding capacity increases if protein is restricted in their diet. PLoS Biol  2024;22:e3002800. PubMed PMC

Seltmann  A, Czirják  GÁ, Courtiol  A  et al.  Habitat disturbance results in chronic stress and impaired health status in forest-dwelling paleotropical bats. Conserv Physiol  2017;5:cox020. PubMed PMC

Worsley  SF, Videvall  E, Harrison  XA  et al.  Probing the functional significance of wild animal microbiomes using omics data. Funct Ecol  2024;38:2329–49.

Ferreira  SCM, Veiga  MM, Hofer  H  et al.  Noninvasively measured immune responses reflect current parasite infections in a wild carnivore and are linked to longevity. Ecology and Evolution  2021;11:7685–99. PubMed PMC

Roffler  AA, Maurer  DP, Lunn  TJ  et al.  Bat humoral immunity and its role in viral pathogenesis, transmission, and zoonosis. Front Immunol  2024;15:1269760. 10.3389/fimmu.2024.1269760 PubMed DOI PMC

Donaldson  EF, Haskew  AN, Gates  JE  et al.  Metagenomic analysis of the Viromes of three north American bat species: viral diversity among different bat species that share a common habitat. J Virol  2010;84:13004–18. PubMed PMC

Wang  J, Pan  Y, Yang  L  et al.  Individual bat virome analysis reveals co-infection and spillover among bats and virus zoonotic potential. Nat Commun  2023;14:4079. PubMed PMC