# Shotgun metagenomic analysis of the oral microbiomes of children with noma

## TL;DR

This study uses metagenomic sequencing to identify unique oral bacteria in children with noma, highlighting a new Treponema species and antibiotic resistance patterns.

## Contribution

The first deep shotgun metagenomic analysis of noma oral microbiomes, identifying a novel Treponema species and microbial dysbiosis signatures.

## Key findings

- Noma oral microbiomes show enrichment of Treponema, Porphyromonas, and Bacteroides, and depletion of Streptococcus and Rothia.
- A novel Treponema species, Treponema sp. A, was detected in 15 of 19 noma cases and absent in healthy controls.
- High levels of antibiotic resistance genes, especially to beta-lactams and metronidazole, were found in noma metagenomes.

## Abstract

Noma is a rapidly progressive orofacial gangrene that predominantly affects children living in extreme poverty. Despite its documentation since antiquity and its designation as a World Health Organisation Neglected Tropical Disease in 2023, the microbiological cause of noma remains poorly understood, with no specific organisms confidently identified as definitive aetiological agents. Here, we present the first deep shotgun metagenomic profiling of oral saliva microbiomes from 19 Nigerian children with acute noma. Our analyses of this preliminary study reveal marked microbial dysbiosis in noma microbiomes, with machine learning and multivariate statistical analyses indicating significant enrichment of Treponema, Porphyromonas, and Bacteroides, alongside depletion of Streptococcus and Rothia, as key microbial signatures of noma disease. From the dataset we recovered 40 high-quality Treponema metagenome assembled genomes (MAGs) spanning 19 species, 14 of which were novel. Notably, a novel species designated Treponema sp. A was detected in 15 of the 19 noma participants and was entirely absent from an internationally representative set of healthy saliva metagenomes. Re-analysis of previously published 16S rRNA datasets from children with noma in Niger also revealed Treponema sp. A to be highly prevalent in noma cases but extremely rare in controls. While these findings highlight Treponema, particularly Treponema sp. A, as an organism of interest and a potential contributor to noma pathogenesis, further comprehensive studies will be required to confirm this association and to clarify whether it reflects a causal role and/or is a genuine marker of noma dysbiosis. Additionally, analysis of antimicrobial resistance determinants detected in noma metagenomes revealed concerning levels of resistance to antibiotics commonly used in noma treatment, particularly β-lactams and metronidazole, especially among Prevotella spp. These findings provide the first high-resolution microbial framework for noma and offer a foundation for future research into its pathogenesis and the development of novel diagnostics, therapeutics, and preventive strategies in endemic settings.

Noma is a rapidly progressing necrotic disease that destroys the tissues of the mouth and face, mainly affecting children living in abject poverty. Although antibiotic treatment can be lifesaving, the microbes involved in noma are still largely unknown, making prevention and early diagnosis difficult. To help address this, we used metagenomic DNA sequencing to profile bacteria from the mouths of 19 Nigerian children with noma treated at the Noma Children’s Hospital in Sokoto, and compared these results with publicly available datasets from healthy individuals. The oral microbiomes of children with noma were remarkably different from healthy controls, with higher levels of certain bacterial species including Treponema, Porphyromonas, and Bacteroides and lower levels of bacteria commonly seen in healthy oral cavities, including Streptococcus and Rothia. We also identified a previously undescribed Treponema species in oral microbiomes of children with noma in this study and found it was also common in earlier noma samples from an independent study in Niger. Finally, we detected genes associated with resistance to antibiotics commonly used to treat noma, including beta-lactams and metronidazole. These findings provide a foundation for larger studies which will hopefully one day lead to diagnostics, targeted therapies, and preventive strategies for noma in endemic settings.