Abstract

This study examined gut colonization patterns and host responses to fecal microbiota transplantation (FMT) by different administration routes after preterm birth. In two separate experiments, cesarean-delivered, preterm pigs were administered combined oral + rectal, or exclusively rectal donor feces, and compared with saline controls. After 5 days, stomach and colon bacterial compositions were determined by 16S rRNA gene amplicon sequencing, and organic acid metabolites measured. Further, gut pathology, mucosa bacterial adherence, and goblet cell density were assessed. FMT increased the relative abundance of obligate anaerobes in the colon without affecting total bacterial load. Bacteroides colonized recipients despite low abundance in the donor feces, whereas highly abundant Prevotella and Ruminococcaceae did not. Further, FMT changed carbohydrate metabolism from lactate to propionate production thereby increasing colonic pH. Besides, FMT preserved goblet cell mucin stores and reduced necrotizing enterocolitis incidence. Only rectal FMT increased the stomach-to-colon pH gradient and resistance to mucosa bacterial adhesion. Conversely, oral + rectal FMT increased bacterial adhesion, internal organ colonization, and overall mortality. Our results uncovered distinctions in bacterial colonization patterns along the gastrointestinal tract, as well as host tolerability between oral and rectal FMT administration in preterm newborns. Besides, FMT showed the potential to prevent necrotizing enterocolitis.

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Acknowledgements

We thank Jane Povlsen, Kristina Møller, and Elin Skytte for assistance with animal caretaking and laboratory analyses.

Funding

This work was supported by Innovation Fund Denmark and the German Academic Exchange Service.

Data availability

Bacterial 16S amplicon sequencing data have been deposited in European Nucleotide Archive (accession number: PRJEB26476).

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Affiliations

  1. Department of Veterinary and Animal Sciences, Comparative Pediatrics and Nutrition, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark

    • Anders Brunse
    • , Lena Martin
    • , Lars Christensen
    • , Malene Skovsted Cilieborg
    • , Per Torp Sangild
    •  & Thomas Thymann
  2. Institute of Animal Nutrition, Freie Universität Berlin, Berlin, Germany

    • Lena Martin
    •  & Robert Pieper
  3. Department of Food Science, Faculty of Science, University of Copenhagen, Frederiksberg, Denmark

    • Torben Sølbeck Rasmussen
    • , Maria Wiese
    • , Bekzod Khakimov
    •  & Dennis Sandris Nielsen

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The authors declare that they have no conflict of interest.

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Correspondence to Thomas Thymann.

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DOI

https://doi.org/10.1038/s41396-018-0301-z