Effects of artificially introduced <i>Enterococcus faecalis</i> strains in experimental necrotizing enterocolitis

Grishin, Anatoly; Delaplain, Patrick T.; Bell, Brandon; Wang, J.; Isani, Mubina; Zhang, E.; Gayer, Christopher P.; Ford, Henri R.

doi:10.1101/623512

Cited by 1 publication

(1 citation statement)

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“…The remaining case has a microbiota dominated by enterococci, which lack the potential to stimulate TLR4 via LPS, and are not amongst the extreme low-CpG organisms. This effect may be species or strain speci c as rodent models have demonstrated that certain strains of Enterococcus faecalis are protective against NEC, whilst other strains are associated with the development of NEC [18]. This case may therefore represent a separate aetiology that is not widely represented in our cohort.…”

Section: Discussionmentioning

confidence: 95%

Premature Neonatal Gut Microbial Community Patterns Supporting An Epithelial TLR-Mediated Pathway For Necrotizing Enterocolitis

Shaw

Sim

Rose

et al. 2021

Preprint

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Background: Necrotising enterocolitis (NEC) is a devastating bowel disease, primarily affecting premature infants, with a poorly understood aetiology. Prior studies have found associations in different cases with an overabundance of particular elements of the faecal microbiota (in particular Enterobacteriaceae or Clostridium perfringens), but there has been no explanation for the different results found in different cohorts. Immunological studies have indicated that stimulation of the TLR4 receptor is involved in development of NEC, with TLR4 signalling being antagonised by the activated TLR9 receptor. We speculated that differential stimulation of these two components of the signalling pathway by different microbiota might explain the dichotomous findings of microbiota-centered NEC studies. Here we used shotgun metagenomic sequencing and qPCR to characterise the faecal microbiota community of infants prior to NEC onset and in a set of matched controls. Logistic regression was used to segregate cases from control samples using both microbial and clinical data.Results: We found that the infants suffering from NEC fell into two groups based on their microbiota; one with relatively low levels of CpG DNA in bacterial genomes and the other with high abundances of organisms expressing LPS. The identification of these characteristic communities was reproduced using an external metagenomic validation dataset. We suggest that these two patterns represent the stimulation of a common pathway at extremes; the LPS leading to overstimulation of TLR4, whilst low levels of CpG fail to sufficiently stimulate TLR9. Conclusions: The identified microbial community patterns support the concept of NEC resulting from TLR-mediated pathways. Identification of these signals suggests characteristics of the gastrointestinal microbial community to be avoided to prevent NEC. Potential pre- or pro-biotic treatments may be designed to optimise TLR signalling.

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Section: Discussionmentioning

confidence: 95%