Delivery mode impacts gut bacteriophage colonization during infancy.

Country of Publication: United States NLM ID: 101767986 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: medRxiv Subsets: PubMed not MEDLINE

Background: Cesarean section delivery is associated with altered early-life bacterial colonization and later adverse inflammatory and immune health outcomes. Although gut bacteriophages can alter gut microbiome composition and impact host immune responses, little is known about how delivery mode impacts bacteriophage colonization over time. To begin to address this we examined how delivery mode affected bacteriophage colonization over the first two years of life.
Results: Shotgun metagenomic sequencing was conducted on 272 serial stool samples from 55 infants, collected at 1-2 days of life and 2, 6, 12 and 24 months. 33/55 (60%) infants were born by vaginal delivery. DNA viruses were identified, and by host inference, 94% of the viral sequences were found to be bacteriophages. Alpha diversity of the virome was increased in vaginally delivered infants compared to cesarean section delivered infants at 2 months (Shannon index, p=0.022). Beta diversity significantly differed by delivery mode at 2, 6, and 12 months when stratified by peripartum antibiotic use (Bray-Curtis dissimilarity, all p<0.05). Significant differentially abundant predicted bacteriophage hosts by delivery mode were seen at all time points. Moreover, there were differences in predicted bacteriophage functional gene abundances up to 24 months by delivery mode. Many of the functions considered to play a role in host response were increased in vaginal delivery.
Conclusions: Clear differences in bacteriophage composition and function were seen by delivery mode over the first two years of life. Given that phages are known to affect host immune response, our results suggest that future investigation into how delivery mode may lead to adverse inflammatory outcomes should not only include bacterial microbial colonization but also the potential role of bacteriophages and transkingdom interactions.
Competing Interests: Competing interests: The authors declare that they have no competing interests.

Science. 2022 May 27;376(6596):945-950. (PMID: 35617387)
Microbiome. 2018 Jun 14;6(1):107. (PMID: 29903041)
PeerJ. 2018 May 7;6:e4694. (PMID: 29761040)
Cell Host Microbe. 2023 Mar 8;31(3):447-460.e6. (PMID: 36893737)
Nat Med. 2015 Oct;21(10):1228-34. (PMID: 26366711)
Science. 2020 Aug 21;369(6506):936-942. (PMID: 32820119)
Nat Microbiol. 2023 May;8(5):986-998. (PMID: 37037943)
Nat Methods. 2021 Apr;18(4):366-368. (PMID: 33828273)
Gut Microbes. 2023 Jan-Dec;15(1):2203969. (PMID: 37096914)
Science. 2016 Apr 29;352(6285):539-44. (PMID: 27126036)
Antimicrob Agents Chemother. 2019 Jul 25;63(8):. (PMID: 31182526)
Obes Rev. 2015 Apr;16(4):295-303. (PMID: 25752886)
Cell Host Microbe. 2023 Feb 8;31(2):187-198.e3. (PMID: 36758519)
EBioMedicine. 2021 Jul;69:103475. (PMID: 34256346)
Cell Host Microbe. 2015 May 13;17(5):690-703. (PMID: 25974306)
Cell Rep Med. 2020 Dec 22;1(9):100156. (PMID: 33377127)
mSystems. 2018 May 15;3(3):. (PMID: 29795809)
Nature. 2020 May;581(7809):470-474. (PMID: 32461640)
Sci Transl Med. 2016 Jun 15;8(343):343ra82. (PMID: 27306664)
Proc Natl Acad Sci U S A. 2022 Mar 29;119(13):e2114619119. (PMID: 35320047)
Gut. 2022 Nov;71(11):2371-2373. (PMID: 35135843)
Trends Microbiol. 2023 Oct;31(10):1058-1071. (PMID: 37198061)
Nat Rev Gastroenterol Hepatol. 2018 Apr;15(4):197-205. (PMID: 29362469)
Cell. 2014 Aug 14;158(4):705-721. (PMID: 25126780)
Microbiome. 2019 Dec 10;7(1):156. (PMID: 31823811)
Int J Environ Res Public Health. 2020 Oct 31;17(21):. (PMID: 33142727)
Microorganisms. 2020 Jan 27;8(2):. (PMID: 32012716)
Gut. 2020 Dec;69(12):2122-2130. (PMID: 32165408)

K23 HD099240 United States HD NICHD NIH HHS

Keywords: bacteriophages; cesarean section; delivery mode; infant; microbiome; vaginal delivery; virome

Date Created: 20231128 Latest Revision: 20231207

20231207

PMC10680904

10.1101/2023.11.13.23298307

38014162