Together with our collaborators in Tromsø in Norway, we published a paper over the weekend in eBioMedicine describing the early colonization patterns of preterm infants, both in terms of the microbes that arrive early to the infants, but also in terms of the antibiotic resistance genes they carry.

In the paper (1), which is a continuation of an earlier study by part of the team (2), we analysed metagenomic data from six Norwegian neonatal intensive care units to better understand the bacterial microbiota of infants born preterm or on term and receiving different treatments. These groups included probiotic-supplemented and antibiotic-exposed extremely preterm infants (n = 29), antibiotic-exposed very preterm infants (n = 25), antibiotic-unexposed very preterm infants (n = 8), and antibiotic-unexposed full-term infants (n = 10). Stool samples were collected from the infants after 7, 28, 120, and 365 days of life and were analysed using shotgun metagenomics. We were particularly interested in the maturation of the preterm infant microbiome into a ‘normal’ healthy gut microbiome, and the colonization with bacteria carrying antibiotic resistance genes.

We found that microbiota maturation was largely determined by the length of hospitalisation for the infants and how much preterm they were. The use of probiotics rendered the gut microbiota and resistome of extremely preterm infants more alike to term infants on day 7 and partially restored the loss of species interconnectivity and stability associated with preterm delivery. Finally, colonisation with Escherichia coli was associated with the highest number of antibiotic-resistance genes in the infant microbiomes, followed by Klebsiella pneumoniae and Klebsiella aerogenes.

Being born very preterm, along with prolonged hospitalisation and frequent antibiotic use alters early life resistome and mobilome, leading to an increased gut carriage of antibiotic resistance genes and mobile genetic elements. On the other hand, the effect of probiotics was not unidirectional. Probiotics decreased resistome burden, but at the same time the bacterial strains in the probiotics appear to promote the activity of mobile genetic elements. Here, further study of the gut microbiota is necessary to be able to design strategies aiming to lower disease risk in vulnerable preterm infants.

As mentioned, this study was a collaboration with Veronika Pettersen‘s group in Tromsø, particularly Ahmed Bargheet, who have done a fabulous job on the bioinformatics and analysis of this study. I hope that we will continue this collaboration in the future (first step will be me visting Tromsø again in June!) This also continues a nice little “sidetrack” of the group’s research into the early life microbiome – previously represented by the work of Katariina Pärnänen (3) and Tove Wikström‘s vaginal microbiome study (4), which is a very interesting and relevant subject in terms of both medicine and microbial ecology. We are also setting up new collaborations in this area, so I hope that more will come out of this track in the next couple of years.

Finally, thank you Veronika for inviting me to participate in this great project!

References

  1. Bargheet A, Klingenberg C, Esaiassen E, Hjerde E, Cavanagh JP, Bengtsson-Palme J, Pettersen VK: Development of early life gut resistome and mobilome across gestational ages and microbiota-modifying treatments. eBio Medicine, 92, 104613 (2023). doi: 10.1016/j.ebiom.2023.104613
  2. Esaiassen E, Hjerde E, Cavanagh JP, Pedersen T, Andresen JH, Rettedal SI, Støen R, Nakstad B, Willassen NP, Klingenberg C: Effects of Probiotic Supplementation on the Gut Microbiota and Antibiotic Resistome Development in Preterm Infants. Frontiers in Pediatrics, 16, 6, 347 (2018). doi: 10.3389/fped.2018.00347
  3. Pärnänen K, Karkman A, Hultman J, Lyra C, Bengtsson-Palme J, Larsson DGJ, Rautava S, Isolauri E, Salminen S, Kumar H, Satokari R, Virta M: Maternal gut and breast milk microbiota affect infant gut antibiotic resistome and mobile genetic elements. Nature Communications, 9, 3891 (2018). doi: 10.1038/s41467-018-06393-w
  4. Wikström T, Abrahamsson S, Bengtsson-Palme J, Ek CJ, Kuusela P, Rekabdar E, Lindgren P, Wennerholm UB, Jacobsson B, Valentin L, Hagberg H: Microbial and human transcriptome in vaginal fluid at midgestation: association with spontaneous preterm delivery. Clinical and Translational Medicine, 12, 9, e1023 (2022). doi: 10.1002/ctm2.1023