Baby-Associated MicroBiota of the Intestine (BAMBI) — an example from the clinic

Necrotising enterocolitis (NEC) is one of the most devastating gastro-intestinal diseases affecting pre-term and low birth- weight babies1. Microbial dysbiosis (imbalance) has been established as the most likely underlying cause of the disease2. Previous studies have revealed that pre-term babies suffering from NEC had more potentially pathogenic bacteria and less of the beneficial Bifidobacterium bifidum2.

Dr. Matthew Clark and Dr. Richard Leggett’s teams at the Earlham Institute in Norwich, UK, are utilising metagenomic nanopore sequencing to profile pre-term infant gut microbiota, identifying not just species but also quantifying them and profiling their antimicrobial resistance (AMR) genes3.

Nanopore sequencing allowed pathogen identification and AMR profiling within 1 hour of sequencing.

Through a time-course experiment, the team was able to observe the impact of probiotic and antibiotic treatments on microbiota composition3. As the probiotic was administered, the amount of B. bifidum (identified to the species level) in the baby’s gut increased, with both long read nanopore sequencing and short-read platforms giving similar profiles.

Interestingly, the researchers also noted that the nanopore metagenomic sequencing approach allowed more detailed taxonomic assignment when compared with 16S rRNA analysis using a short-read sequencing platform, which failed to differentiate members of the Enterobacteriaceae family3.

Utilising real-time analysis of a faecal sample from a critically ill infant, the team were able to confidently call the presence of the pathogen Klebsiella pneumoniae along with corresponding AMR profiles within 1 hour of sequencing3.

Nanopore sequencing data was found to be of similar quality to that provided by short-read sequencing technology but, critically, it could be generated in a fraction of the time, requiring just 5 hours as opposed to 39 hours for the short-read technology.

In conclusion, the researchers highlighted how nanopore technology could, in the future, be applied to clinical applications:

‘Our results demonstrate that MinION sequencers offer the ability to progress from clinical samples to a potential tailored patient antimicrobial treatment in just a few hours’3.

This case study is taken from the Microbiome white paper.

1. Deshpande, G., Rao, S., Patole, S. & Bulsara, M. Updated Meta-analysis of probiotics for preventing necrotizing enterocolitis in preterm neonates. Pediatrics 125, 921 (2010).

2. Clark, M. MinION metagenomics: from mock communities to clinical samples. Presentation (2016). Available at: https://vimeo.com/169892664 [Accessed: 24 January 2018]

3. Leggett, R.M. et al. Rapid MinION metagenomic profiling of the preterm infant gut microbiota to aid in pathogen diagnostics. BioRxiv 180406 (2017).