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Open Access 01-12-2023 | Autism Spectrum Disorder | Research

Children with autism show differences in the gut DNA virome compared to non-autistic children: a case control study

Authors: Aina Qu, Boyang Duan, Yue Wang, Zhenzhen Cui, Nuochen Zhang, De Wu

Published in: BMC Pediatrics | Issue 1/2023

Abstract

Background

Several previous studies have identified a potential role that the gut microbiome can play in autism spectrum disorder (ASD) in children, but little is known about how variations in the virome may be involved in ASD. We aimed to understand the changes in the gut DNA virome of children with ASD.

Methods

A case–control study was presented, in which 13 two-children families were observed while considering the age, mode of birth, history of antibiotic use, and vaccination history to minimize the influence of confounding factors. DNA viral metagenomic sequencing was successfully performed on stool samples from 11 children with ASD and 12 healthy non-ASD children. The basic composition and gene function of the participants' fecal DNA virome were detected and analyzed. Finally, the abundance and diversity of the DNA virome of children with ASD and their healthy siblings were compared.

Results

The gut DNA virome in children aged 3–11 years was found to be dominated by the Siphoviridae family of Caudovirales. The proteins encoded by the DNA genes mainly carry out the functions of genetic information transmission and metabolism. Compared the gut DNA virome of ASD and healthy non-ASD children, their abundance of Caudovirales and Petitvirales both showed a significant negative correlation (r = -0.902, P < 0.01), there was no statistically significant difference in the relative abundance of viruses at the order and family levels, and a difference in the relative abundance at the genus level for Skunavirus (Ζ = -2.157, P = 0.031). Viral α diversity was reduced in children with ASD, but α diversity and β diversity did not differ statistically between groups.

Conclusions

This study indicates that elevated Skunavirus abundance and decreased α diversity in the gut DNA virulence group of children with ASD, but no statistically significant difference in the change in alpha and beta diversity. This provides preliminary cumulative information on virological aspects of the relationship between the microbiome and ASD, and should benefit future multi-omics and large sample studies on the gut microbes in children with ASD.

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Lord C, Elsabbagh M, Baird G, Veenstra-Vanderweele J. Autism spectrum disorder. Lancet. 2018;392(10146):508–20. https://doi.org/10.1016/S0140-6736(18)31129-2.CrossRefPubMedPubMedCentral

Solmi M, Song M, Yon DK, Lee SW, Fombonne E, Kim MS, Park S, Lee MH, Hwang J, Keller R, et al. Incidence, prevalence, and global burden of autism spectrum disorder from 1990 to 2019 across 204 countries. Mol Psychiatry. 2022;27(10):4172–80. https://doi.org/10.1038/s41380-022-01630-7.CrossRefPubMed

Lai MC, Lombardo MV, Baron-Cohen S. Autism Lancet. 2014;383(9920):896–910. https://doi.org/10.1016/S0140-6736(13)61539-1.CrossRefPubMed

Tan C, Frewer V, Cox G, Williams K, Ure A. Prevalence and age of onset of regression in children with autism spectrum disorder: a systematic review and meta-analytical update. Autism Res. 2021;14(3):582–98. https://doi.org/10.1002/aur.2463.CrossRefPubMed

Rogge N, Janssen J. The economic costs of autism spectrum disorder: a literature review. J Autism Dev Disord. 2019;49(7):2873–900. https://doi.org/10.1007/s10803-019-04014-z.CrossRefPubMed

Yu Y, Zhao F. Microbiota-gut-brain axis in autism spectrum disorder. J Genet Genomics. 2021;48(9):755–62. https://doi.org/10.1016/j.jgg.2021.07.001.CrossRefPubMed

Averina OV, Kovtun AS, Polyakova SI, Savilova AM, Rebrikov DV, Danilenko VN. The bacterial neurometabolic signature of the gut microbiota of young children with autism spectrum disorders. J Med Microbiol. 2020;69(4):558–71. https://doi.org/10.1099/jmm.0.001178.CrossRefPubMed

Alharthi A, Alhazmi S, Alburae N, Bahieldin A. The human gut microbiome as a potential factor in autism spectrum disorder. Int J Mol Sci. 2022;23(3):1363. https://doi.org/10.3390/ijms23031363.CrossRefPubMedPubMedCentral

Vemuri R, Shankar EM, Chieppa M, Eri R, Kavanagh K. Beyond just bacteria: functional biomes in the gut ecosystem including virome, mycobiome, archaeome and helminths. Microorganisms. 2020;8(4):483. https://doi.org/10.3390/microorganisms8040483.CrossRefPubMedPubMedCentral

10.

Wang Z, Guo K, Liu Y, Huang C, Wu M. Dynamic impact of virome on colitis and colorectal cancer: Immunity, inflammation, prevention and treatment. Semin Cancer Biol. 2022;86(Pt 2):943–54. https://doi.org/10.1016/j.semcancer.2021.10.004.CrossRefPubMed

11.

Ly M, Jones MB, Abeles SR, Santiago-Rodriguez TM, Gao J, Chan IC, Ghose C, Pride DT. Transmission of viruses via our microbiomes. Microbiome. 2016;4(1):64. https://doi.org/10.1186/s40168-016-0212-z.CrossRefPubMedPubMedCentral

12.

Yan Q, Wang Y, Chen X, Jin H, Wang G, Guan K, Zhang Y, Zhang P, Ayaz T, Liang Y, et al. Characterization of the gut DNA and RNA Viromes in a Cohort of Chinese Residents and Visiting Pakistanis. Virus Evol. 2021;7(1):veab022. https://doi.org/10.1093/ve/veab022.CrossRefPubMedPubMedCentral

13.

American Psychiatric Association. American Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Washington: American Psychiatric Pub; 2013.CrossRef

14.

Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics. 2014;30(15):2114–20. https://doi.org/10.1093/bioinformatics/btu170.CrossRefPubMedPubMedCentral

15.

Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009;25(14):1754–60. https://doi.org/10.1093/bioinformatics/btp324.CrossRefPubMedPubMedCentral

16.

Li D, Luo R, Liu CM, Leung CM, Ting HF, Sadakane K, Yamashita H, Lam TW. MEGAHIT v1.0: A fast and scalable metagenome assembler driven by advanced methodologies and community practices. Methods. 2016;102:3–11. https://doi.org/10.1016/j.ymeth.2016.02.020.CrossRefPubMed

17.

Nayfach S, Camargo AP, Schulz F, Eloe-Fadrosh E, Roux S, Kyrpides NC. CheckV assesses the quality and completeness of metagenome-assembled viral genomes. Nat Biotechnol. 2021;39(5):578–85. https://doi.org/10.1038/s41587-020-00774-7.CrossRefPubMed

18.

Guo J, Bolduc B, Zayed AA, Varsani A, Dominguez-Huerta G, Delmont TO, Pratama AA, Gazitúa MC, Vik D, Sullivan MB, Roux S. VirSorter2: a multi-classifier, expert-guided approach to detect diverse DNA and RNA viruses. Microbiome. 2021;9(1):37. https://doi.org/10.1186/s40168-020-00990-y.CrossRefPubMedPubMedCentral

19.

Pons JC, Paez-Espino D, Riera G, Ivanova N, Kyrpides NC, Llabrés M. VPF-Class: Taxonomic assignment and host prediction of uncultivated viruses based on viral protein families [published online ahead of print, 2021 Jan 20]. Bioinformatics. 2021;37(13):1805–13. https://doi.org/10.1093/bioinformatics/btab026.CrossRefPubMedPubMedCentral

20.

Seemann T. Prokka: rapid prokaryotic genome annotation. Bioinformatics. 2014;30(14):2068–9. https://doi.org/10.1093/bioinformatics/btu153.CrossRefPubMed

21.

Kanehisa M, Goto S. KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 2000;28(1):27–30. https://doi.org/10.1093/nar/28.1.27.CrossRefPubMedPubMedCentral

22.

Buchfink B, Xie C, Huson DH. Fast and sensitive protein alignment using DIAMOND. Nat Methods. 2015;12(1):59–60. https://doi.org/10.1038/nmeth.3176.CrossRefPubMed

23.

Beller L, Deboutte W, Vieira-Silva S, et al. The virota and its transkingdom interactions in the healthy infant gut. Proc Natl Acad Sci U S A. 2022;119(13):e2114619119. https://doi.org/10.1073/pnas.2114619119.CrossRefPubMedPubMedCentral

24.

Shkoporov AN, Clooney AG, Sutton TDS, Ryan FJ, Daly KM, Nolan JA, McDonnell SA, Khokhlova EV, Draper LA, Forde A, et al. The Human Gut Virome Is Highly Diverse, Stable, and Individual Specific. Cell Host Microbe. 2019;26(4):527–41. https://doi.org/10.1016/j.chom.2019.09.009.CrossRefPubMed

25.

Mayneris-Perxachs J, Castells-Nobau A, Arnoriaga-Rodríguez M, Garre-Olmo J, Puig J, Ramos R, Martínez-Hernández F, Burokas A, Coll C, Moreno-Navarrete JM, et al. Caudovirales bacteriophages are associated with improved executive function and memory in flies, mice, and humans. Cell Host Microbe. 2022;30(3):340–56. https://doi.org/10.1016/j.chom.2022.01.013.CrossRefPubMed

26.

Lemay ML, Maaß S, Otto A, Hamel J, Plante PL, Rousseau GM, Tremblay DM, Shi R, Corbeil J, Gagné SM, et al. A lactococcal phage protein promotes viral propagation and alters the host proteomic response during infection. Viruses. 2020;12(8):797. https://doi.org/10.3390/v12080797.CrossRefPubMedPubMedCentral

27.

Doré L, Pageau G, Bourque-Leblanc F, Dupuis MÈ, Lessard-Hurtubise R, Lacasse G, Plante PL, Labrie S, P Jolicoeur A, Rousseau GM, et al. Complete Genome Sequences of 10 Lactococcal Skunavirus Phages Isolated from Cheddar Cheese Whey Samples in Canada. Microbiol Resour Announc. 2021;10(15):e00098-21. https://doi.org/10.1128/MRA.00098-21.CrossRefPubMedPubMedCentral

28.

Ruiz-Cruz S, Parlindungan E, ErazoGarzon A, Alqarni M, Lugli GA, Ventura M, van Sinderen D, Mahony J. Lysogenization of a lactococcal host with three distinct temperate phages provides homologous and heterologous phage resistance. Microorganisms. 2020;8(11):1685. https://doi.org/10.3390/microorganisms8111685.CrossRefPubMedPubMedCentral

29.

Shkoporov AN, Hill C. Bacteriophages of the human gut: the “Known Unknown” of the Microbiome. Cell Host Microbe. 2019;25(2):195–209. https://doi.org/10.1016/j.chom.2019.01.017.

30.

Moreno-Gallego JL, Chou SP, Di Rienzi SC, Goodrich JK, Spector TD, Bell JT, Youngblut ND, Hewson I, Reyes A, Ley RE. Virome diversity correlates with intestinal microbiome diversity in adult monozygotic twins. Cell Host Microbe. 2019;25(2):261–72. https://doi.org/10.1016/j.chom.2019.01.019.CrossRefPubMedPubMedCentral

31.

Son JS, Zheng LJ, Rowehl LM, Tian X, Zhang Y, Zhu W, Litcher-Kelly L, Gadow KD, Gathungu G, Robertson CE, et al. Comparison of Fecal Microbiota in Children with Autism Spectrum Disorders and Neurotypical Siblings in the Simons Simplex Collection. PLoS One. 2015;10(10):e0137725. https://doi.org/10.1371/journal.pone.0137725.CrossRefPubMedPubMedCentral

32.

Yap CX, Henders AK, Alvares GA, Wood DLA, Krause L, Tyson GW, Restuadi R, Wallace L, McLaren T, Hansell NK, et al. Autism-related dietary preferences mediate autism-gut microbiome associations. Cell. 2021;184(24):5916–31. https://doi.org/10.1016/j.cell.2021.10.015.CrossRefPubMed

33.

Nusbaum DJ, Sun F, Ren J, Zhu Z, Ramsy N, Pervolarakis N, Kunde S, England W, Gao B, Fiehn O, et al. Gut microbial and metabolomic profiles after fecal microbiota transplantation in pediatric ulcerative colitis patients. FEMS Microbiol Ecol. 2018;94(9):fiy133. https://doi.org/10.1093/femsec/fiy133.CrossRefPubMedPubMedCentral

34.

Tokarz R, Hyams JS, Mack DR, Boyle B, Griffiths AM, LeLeiko NS, Sauer CG, Shah S, Markowitz J, Baker SS, et al. Characterization of Stool Virome in Children Newly Diagnosed With Moderate to Severe Ulcerative Colitis. Inflamm Bowel Dis. 2019;25(10):1656–62. https://doi.org/10.1093/ibd/izz099.CrossRefPubMedPubMedCentral

35.

Berding K, Donovan SM. Diet can impact microbiota composition in children with autism spectrum disorder. Front Neurosci. 2018;12:515. https://doi.org/10.3389/fnins.2018.00515.CrossRefPubMedPubMedCentral

36.

Gondalia SV, Palombo EA, Knowles SR, Cox SB, Meyer D, Austin DW. Molecular characterisation of gastrointestinal microbiota of children with autism (with and without gastrointestinal dysfunction) and their neurotypical siblings. Autism Res. 2012;5(6):419–27. https://doi.org/10.1002/aur.1253.CrossRefPubMed

37.

Yang K, Niu J, Zuo T, Sun Y, Xu Z, Tang W, Liu Q, Zhang J, Ng EKW, Wong SKH, et al. Alterations in the gut virome in obesity and type 2 diabetes mellitus. Gastroenterology. 2021;161(4):1257–69. https://doi.org/10.1053/j.gastro.2021.06.056.CrossRefPubMed

38.

Bombin A, Yan S, Bombin S, Mosley JD, Ferguson JF. Obesity influences composition of salivary and fecal microbiota and impacts the interactions between bacterial taxa. Physiol Rep. 2022;10(7):e15254. https://doi.org/10.14814/phy2.15254.CrossRefPubMedPubMedCentral

Title: Children with autism show differences in the gut DNA virome compared to non-autistic children: a case control study
Authors: Aina Qu
Boyang Duan
Yue Wang
Zhenzhen Cui
Nuochen Zhang
De Wu
Publication date: 01-12-2023
Publisher: BioMed Central
Keyword: Autism Spectrum Disorder
Published in: BMC Pediatrics / Issue 1/2023
Electronic ISSN: 1471-2431
DOI: https://doi.org/10.1186/s12887-023-03981-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Children with autism show differences in the gut DNA virome compared to non-autistic children: a case control study

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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