Acute appendicitis is associated with appendiceal microbiome changes including elevated Campylobacter jejuni levels

Objectives To compare the appendiceal microbiomes and examine the prevalence of Campylobacter species in the appendices of adult subjects with confirmed acute non-perforated appendicitis and controls with healthy appendices.Design Archived samples of formalin-fixed paraffin-embedded appendiceal tiss...

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Main Authors: Sun Jung Oh, Maya Pimentel, Gabriela G S Leite, Shreya Celly, Maria Jesus Villanueva-Millan, Isabela Lacsina, Brennan Chuang, Gonzalo Parodi, Walter Morales, Stacy Weitsman, Tahli Singer-Englar, Gillian M Barlow, Jing Zhai, Nipaporn Pichestshote, Ali Rezaie, Ruchi Mathur, Mark Pimentel
Format: Article
Language:English
Published: BMJ Publishing Group 2020-12-01
Series:BMJ Open Gastroenterology
Online Access:https://bmjopengastro.bmj.com/content/7/1/e000412.full
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author Sun Jung Oh
Maya Pimentel
Gabriela G S Leite
Shreya Celly
Maria Jesus Villanueva-Millan
Isabela Lacsina
Brennan Chuang
Gonzalo Parodi
Walter Morales
Stacy Weitsman
Tahli Singer-Englar
Gillian M Barlow
Jing Zhai
Nipaporn Pichestshote
Ali Rezaie
Ruchi Mathur
Mark Pimentel
author_facet Sun Jung Oh
Maya Pimentel
Gabriela G S Leite
Shreya Celly
Maria Jesus Villanueva-Millan
Isabela Lacsina
Brennan Chuang
Gonzalo Parodi
Walter Morales
Stacy Weitsman
Tahli Singer-Englar
Gillian M Barlow
Jing Zhai
Nipaporn Pichestshote
Ali Rezaie
Ruchi Mathur
Mark Pimentel
author_sort Sun Jung Oh
collection DOAJ
description Objectives To compare the appendiceal microbiomes and examine the prevalence of Campylobacter species in the appendices of adult subjects with confirmed acute non-perforated appendicitis and controls with healthy appendices.Design Archived samples of formalin-fixed paraffin-embedded appendiceal tissues were obtained from 50 consecutive female subjects who underwent appendectomy for acute, non-perforated appendicitis, and 35 consecutive female controls who underwent incidental appendectomy during gynaecological surgery.Results 16S rRNA gene sequencing revealed that the relative abundances (RAs) of the major phyla in appendiceal tissues (Firmicutes, Proteobacteria, Bacteroidetes, and Actinobacteria) were similar in both groups. Beta diversity was significantly different due to differences in Bacteroidetes and Proteobacteria (p<0.0001). Within Proteobacteria, RAs of classes Alphaproteobacteria (~21%, fold change (FC)=1.31, false discovery rate (FDR) p value=0.03) and Epsilonproteobacteria (~1%, FC=0.25, FDR p value>0.05) were increased in acute appendicitis samples. RAs of unknown genera from families Burkholderiaceae and Enterobacteriaceae were decreased in appendicitis samples, and 14 genera were increased, including Neisseria, Acinetobacter and Campylobacter. Quantitative PCR revealed that levels of Campylobacter jejuni DNA, but not other Campylobacter species or pathogens tested, were significantly higher in appendicitis samples than in controls (p=0.013). Using a cut-off of 0.31 pg/µL, 40% of appendicitis cases and 6% of controls were positive for C. jejuni, indicating specificity of 93.7% (95% Cl 79.2 to 99.2), sensitivity of 40.9% (95% Cl 24.7 to 54.5), and OR of 10.38 (Fisher’s p value=0.0006, 95% Cl 2.3 to 47.4).Conclusions Our findings indicate that Campylobacter jejuni may be a significant cause of acute appendicitis. This supports earlier studies and suggests that targeted antibiotic therapies could be an alternative treatment for a subset of non-complicated acute appendicitis cases.
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spelling doaj-art-9b86b364d03c4ffc8d59964efb08c7b32025-08-20T02:39:21ZengBMJ Publishing GroupBMJ Open Gastroenterology2054-47742020-12-017110.1136/bmjgast-2020-000412Acute appendicitis is associated with appendiceal microbiome changes including elevated Campylobacter jejuni levelsSun Jung Oh0Maya Pimentel1Gabriela G S Leite2Shreya Celly3Maria Jesus Villanueva-Millan4Isabela Lacsina5Brennan Chuang6Gonzalo Parodi7Walter Morales8Stacy Weitsman9Tahli Singer-Englar10Gillian M Barlow11Jing Zhai12Nipaporn Pichestshote13Ali Rezaie14Ruchi Mathur15Mark Pimentel16Medically Associated Science and Technology (MAST) Program, Cedars-Sinai Medical Center, Los Angeles, California, USAMedically Associated Science and Technology (MAST) Program, Cedars-Sinai Medical Center, Los Angeles, California, USAMedically Associated Science and Technology (MAST) Program, Cedars-Sinai Medical Center, Los Angeles, California, USAMedically Associated Science and Technology (MAST) Program, Cedars-Sinai Medical Center, Los Angeles, California, USAMedically Associated Science and Technology (MAST) Program, Cedars-Sinai Medical Center, Los Angeles, California, USAMedically Associated Science and Technology (MAST) Program, Cedars-Sinai Medical Center, Los Angeles, California, USAMedically Associated Science and Technology (MAST) Program, Cedars-Sinai Medical Center, Los Angeles, California, USAMedically Associated Science and Technology (MAST) Program, Cedars-Sinai Medical Center, Los Angeles, California, USAMedically Associated Science and Technology (MAST) Program, Cedars-Sinai Medical Center, Los Angeles, California, USAMedically Associated Science and Technology (MAST) Program, Cedars-Sinai Medical Center, Los Angeles, California, USAMedically Associated Science and Technology (MAST) Program, Cedars-Sinai Medical Center, Los Angeles, California, USAMedically Associated Science and Technology (MAST) Program, Cedars-Sinai Medical Center, Los Angeles, California, USA1 Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaMedically Associated Science and Technology (MAST) Program, Cedars-Sinai Medical Center, Los Angeles, California, USAMedically Associated Science and Technology (MAST) Program, Cedars-Sinai Medical Center, Los Angeles, California, USAMedically Associated Science and Technology (MAST) Program, Cedars-Sinai Medical Center, Los Angeles, California, USACedars-Sinai Medical Center, Los Angeles, California, USAObjectives To compare the appendiceal microbiomes and examine the prevalence of Campylobacter species in the appendices of adult subjects with confirmed acute non-perforated appendicitis and controls with healthy appendices.Design Archived samples of formalin-fixed paraffin-embedded appendiceal tissues were obtained from 50 consecutive female subjects who underwent appendectomy for acute, non-perforated appendicitis, and 35 consecutive female controls who underwent incidental appendectomy during gynaecological surgery.Results 16S rRNA gene sequencing revealed that the relative abundances (RAs) of the major phyla in appendiceal tissues (Firmicutes, Proteobacteria, Bacteroidetes, and Actinobacteria) were similar in both groups. Beta diversity was significantly different due to differences in Bacteroidetes and Proteobacteria (p<0.0001). Within Proteobacteria, RAs of classes Alphaproteobacteria (~21%, fold change (FC)=1.31, false discovery rate (FDR) p value=0.03) and Epsilonproteobacteria (~1%, FC=0.25, FDR p value>0.05) were increased in acute appendicitis samples. RAs of unknown genera from families Burkholderiaceae and Enterobacteriaceae were decreased in appendicitis samples, and 14 genera were increased, including Neisseria, Acinetobacter and Campylobacter. Quantitative PCR revealed that levels of Campylobacter jejuni DNA, but not other Campylobacter species or pathogens tested, were significantly higher in appendicitis samples than in controls (p=0.013). Using a cut-off of 0.31 pg/µL, 40% of appendicitis cases and 6% of controls were positive for C. jejuni, indicating specificity of 93.7% (95% Cl 79.2 to 99.2), sensitivity of 40.9% (95% Cl 24.7 to 54.5), and OR of 10.38 (Fisher’s p value=0.0006, 95% Cl 2.3 to 47.4).Conclusions Our findings indicate that Campylobacter jejuni may be a significant cause of acute appendicitis. This supports earlier studies and suggests that targeted antibiotic therapies could be an alternative treatment for a subset of non-complicated acute appendicitis cases.https://bmjopengastro.bmj.com/content/7/1/e000412.full
spellingShingle Sun Jung Oh
Maya Pimentel
Gabriela G S Leite
Shreya Celly
Maria Jesus Villanueva-Millan
Isabela Lacsina
Brennan Chuang
Gonzalo Parodi
Walter Morales
Stacy Weitsman
Tahli Singer-Englar
Gillian M Barlow
Jing Zhai
Nipaporn Pichestshote
Ali Rezaie
Ruchi Mathur
Mark Pimentel
Acute appendicitis is associated with appendiceal microbiome changes including elevated Campylobacter jejuni levels
BMJ Open Gastroenterology
title Acute appendicitis is associated with appendiceal microbiome changes including elevated Campylobacter jejuni levels
title_full Acute appendicitis is associated with appendiceal microbiome changes including elevated Campylobacter jejuni levels
title_fullStr Acute appendicitis is associated with appendiceal microbiome changes including elevated Campylobacter jejuni levels
title_full_unstemmed Acute appendicitis is associated with appendiceal microbiome changes including elevated Campylobacter jejuni levels
title_short Acute appendicitis is associated with appendiceal microbiome changes including elevated Campylobacter jejuni levels
title_sort acute appendicitis is associated with appendiceal microbiome changes including elevated campylobacter jejuni levels
url https://bmjopengastro.bmj.com/content/7/1/e000412.full
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