Dysbiosis of the Oral Ecosystem in Severe Congenital Neutropenia Patients

Abstract

Purpose: To decipher the underlying immunological mechanisms in predisposition to oral microbial dysbiosis in severe congenital neutropenia (SCN) patients. Experimental Design: Ten SCN patients (5-23 years old) and 12 healthy controls (5-22 years old) are periodontally examined and provided saliva, subgingival plaque, and gingival crevicular fluid (GCF) samples. The SCN patients received oral hygiene therapy and are re-evaluated after 6 months. Antimicrobial peptides HPN1-3 and LL-37 are assessed in saliva by ELISA. Concentration of 30 cytokines is measured in saliva and GCF by human 30-plex panel, while bacterial profiles of saliva and subgingival plaque are assessed using 16S rDNA amplicon sequencing. Results: There is no significant difference in salivary HPN1-3 and LL-37 concentration between the SCN patients and controls. At baseline, clinical, immunological, and microbiological parameters of the patients are indicative of oral ecological dysbiosis. The SCN patients have significantly higher bleeding on probing (BOP)%, GCF volume, and cytokine levels, high bacterial load with low bacterial diversity in saliva. The associations between the microbiome and immunological parameters in the SCN patients differ from those in the healthy individuals. Conclusions and Clinical Relevance: SCN patients have a dysregulated immune response toward commensal oral microbiota, which could be responsible for the observed clinical and microbiological signs of dysbiosis.

Inborn errors of immunity and related microbiome

“…To elucidate the immunological mechanisms of susceptibility to oral microbial dysbiosis in patients with severe congenital neutropenia (SCN), Zaura et al. investigated the oral microbiome in 10 cases of severe congenital neutropenia and observed markedly higher levels of cytokines and high bacterial load with low bacterial diversity in the saliva of patients with SCN ( 101 ). These findings suggest that disrupted immune response to the oral microbiota might be involved in the observed clinical and microbiological manifestations.…”

Microbiocenoses and the State of Local Mucosal Immunity of the Oral Cavity of Children and Adolescents with Liver Diseases

“…Відомо, що надважливу роль у захисті ротової порожнини виконує саме місцевий мукозальний імунітет [8]. При його зниженні виникає стан дисбіозу в ПР, за рахунок якого порушується баланс між мікробними популяціями з частковим їх заміщенням [9]. Хронічні запальні процеси супроводжуються аутоінтоксикацією організму, при якій зазвичай порушується робота імунної системи.…”

The oral microbiome of a family including Papillon-Lefèvre-syndrome patients and clinically healthy members

“…A mutation causing a disruption of the neutrophil elastase enzyme was identified in the previously mentioned SCN patients. In another group of patients with Kostmann syndrome, we find a homozygous mutation of the HAX1 gene that regulates neutrophil apoptosis, which is the most common SCN-related mutation in Turkey, and there is a variant in which neutropenia is not associated with the symptoms of Kostmann syndrome [ 28 , 29 ]. Despite the fact that the level of antimicrobial proteins (HNP1-3, LL-37) in patients treated with G-CSF did not differ compared to the control group, these patients show more severe inflammatory signs, low bacterial diversity with high bacterial load associated with dysbiosis [ 29 ].…”

“…In another group of patients with Kostmann syndrome, we find a homozygous mutation of the HAX1 gene that regulates neutrophil apoptosis, which is the most common SCN-related mutation in Turkey, and there is a variant in which neutropenia is not associated with the symptoms of Kostmann syndrome [ 28 , 29 ]. Despite the fact that the level of antimicrobial proteins (HNP1-3, LL-37) in patients treated with G-CSF did not differ compared to the control group, these patients show more severe inflammatory signs, low bacterial diversity with high bacterial load associated with dysbiosis [ 29 ]. Severe congenital neutropenia treated by bone-marrow transplant may result, however, in functionally intact neutrophils and normal levels of LL-37 in plasma, saliva and neutrophils and, furthermore, periodontally healthy patients [ 30 – 32 ].…”