Host–Microbiota Interactions in the Esophagus During Homeostasis and Allergic Inflammation

Brusilovsky, Michael; Bao, Riyue; Rochman, Mark; Kemter, Andrea M.; Nagler, Cathryn R.; Rothenberg, Marc E.

doi:10.1053/j.gastro.2021.10.002

Cited by 32 publications

(16 citation statements)

References 63 publications

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“…The Differentiated hi subpopulation specifically expresses ribonuclease A family member 7 ( RNASE7 ), a protein that has broad-spectrum antimicrobial activity against bacteria and fungi. Loss of RNASE7 expression may be related to the dysbiosis observed in individuals with active EoE ( 34 , 35 ). Moreover, differentiated cells express peptidyl arginine deiminase (PADI) and transglutaminase (TGM) genes that drive calcium-dependent protein deamination (citrullination) and structural protein crosslinking.…”

Section: Discussionmentioning

confidence: 99%

Single-cell RNA-Seq of human esophageal epithelium in homeostasis and allergic inflammation

et al. 2022

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Inflammation of the esophageal epithelium is a hallmark of eosinophilic esophagitis (EoE), an emerging chronic allergic disease. Herein, we probed human esophageal epithelial cells at single-cell resolution during homeostasis and EoE. During allergic inflammation, the epithelial differentiation program was blocked, leading to loss of KRT6 hi differentiated populations and expansion of TOP2 hi proliferating, DSP hi transitioning, and SERPINB3 hi transitioning populations; however, there was stability of the stem cell–enriched PDPN hi basal epithelial compartment. This differentiation program blockade was associated with dysregulation of transcription factors, including nuclear receptor signalers, in the most differentiated epithelial cells and altered NOTCH-related cell-to-cell communication. Each epithelial population expressed genes with allergic disease risk variants, supporting their functional interplay. The esophageal epithelium differed notably between EoE in histologic remission and controls, indicating that remission is a transitory state poised to relapse. Collectively, our data uncover the dynamic nature of the inflamed human esophageal epithelium and provide a framework to better understand esophageal health and disease.

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Section: Discussionmentioning

confidence: 99%

Single-cell RNA-Seq of human esophageal epithelium in homeostasis and allergic inflammation

et al. 2022

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“…In a mouse model, neonatal oral exposure to a cocktail of broad-spectrum antibiotics led to gradual depletion of endogenous Lachnospiraceae and Bacteroidaceae families of bacteria in all tissues examined, including the esophagus and colon, and a higher relative abundance of inflammation-associated bacteria, including bacteria from the class Mollicutes and the phylum Actinobacteria in the esophagus. Notably, antibiotic treatment promoted type 2 inflammation in this murine model of EoE …”

Section: Discussionmentioning

confidence: 82%

“…Notably, antibiotic treatment promoted type 2 inflammation in this murine model of EoE. 21 Contextualizing our results for acid suppressants is somewhat more difficult. Prematurity increases the likelihood of prophylactic acid suppressant use.…”

Section: Discussionmentioning

confidence: 88%

Maternal and Infant Antibiotic and Acid Suppressant Use and Risk of Eosinophilic Esophagitis

Jensen,

Svane,

Erichsen

et al. 2023

JAMA Pediatr

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ImportanceEosinophilic esophagitis (EoE), a chronic disease with significant patient and health care burden, has increased rapidly in incidence across many countries. Elucidating risk factors for disease development is a priority for health care practitioners and patients.ObjectiveTo evaluate the association of maternal and infant use of antibiotics and acid suppressants with the development of EoE.Design, Setting, and ParticipantsThis was a population-based, case-control study of pediatric EoE (1996-2019) in Denmark using pathology, prescription, birth, inpatient, and outpatient health registry data and with complete ascertainment of all EoE cases among Danish residents born between 1997 and 2018. Study data were analyzed from September 2020 to August 2023.ExposuresMaternal and infant use of antibiotics and acid suppressants, examining medication class, timing, and frequency of use.Main Outcome and MeasureDevelopment of EoE.ResultsIncluded in the study was a total of 392 cases and 3637 sex- and year of birth–matched controls with a median (IQR) age of 11.0 (6.0-15.0) years, 2772 male individuals (68.8%), and 1257 female individuals (31.2%). Compared with children with no antibiotic prescriptions filled during infancy, those with any use of an antibiotic had an associated 40% increase in risk of EoE (adjusted odds ratio [aOR], 1.4; 95% CI, 1.1-1.7). Those with 3 or more prescriptions had an associated 80% increase in risk of EoE (aOR, 1.8; 95% CI, 1.3-2.5). Frequency of maternal antibiotic use was associated with an increased risk (1 prescription: aOR, 1.4; 95% CI, 1.0-1.8; 3≤ prescriptions: aOR, 2.1; 95% CI, 1.4-3.2). Risk was highest for use in the third trimester and in the first 6 months from birth. Any acid suppressant use in infancy was associated with increased risk of EoE (aOR, 15.9; 95% CI, 9.1-27.7). Restriction of cases to those diagnosed at 5 years or older yielded similar results (aOR, 11.6; 95% CI, 5.5-24.8). For maternal use, 3 or more prescriptions were associated with an increased risk of EoE for her offspring (aOR, 5.1; 95% CI, 1.8-14.8).Conclusions and RelevanceMaternal and infant antibiotic use were associated with increased risk of developing EoE, in a dose-response manner, and the magnitude of association was highest for exposure near the time of delivery. Increased risk was also observed with maternal and infant acid suppressant use. Exposure during early life, a period of known developmental susceptibility, may confer the greatest risk and opportunity for risk mitigation.

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“…1,2 Both diseases are characterised by a loss of tolerance towards luminal antigens favoured by microbiota disruption suggesting that they may share similar pathophysiology. 3,4 Associations between the two diseases have been suggested in previous studies, especially the risk of developing EoE in individuals with IBD. 5 However, data regarding the risk of developing IBD in individuals with EoE are scarce.In the current issue of the United European Gastroenterology Journal, Uchida et al assessed the risk of developing IBD in individuals with histopathologic-proven diagnosis of EoE.…”

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confidence: 85%

“…Inflammatory bowel diseases (IBD) and eosinophilic oesophagitis (EoE) are immune‐mediated disorders of the gastrointestinal (GI) tract with an increasing incidence worldwide 1,2 . Both diseases are characterised by a loss of tolerance towards luminal antigens favoured by microbiota disruption suggesting that they may share similar pathophysiology 3,4 . Associations between the two diseases have been suggested in previous studies, especially the risk of developing EoE in individuals with IBD 5 .…”

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confidence: 99%

Inflammatory bowel diseases and eosinophilic oesophagitis: Two overlapping disorders?

Grellier,

Kirchgesner

2023

UEG Journal

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Inflammatory bowel diseases and eosinophilic oesophagitis: Two overlapping disorders?Inflammatory bowel diseases (IBD) and eosinophilic oesophagitis (EoE) are immune-mediated disorders of the gastrointestinal (GI) tract with an increasing incidence worldwide. 1,2 Both diseases are characterised by a loss of tolerance towards luminal antigens favoured by microbiota disruption suggesting that they may share similar pathophysiology. 3,4 Associations between the two diseases have been suggested in previous studies, especially the risk of developing EoE in individuals with IBD. 5 However, data regarding the risk of developing IBD in individuals with EoE are scarce.In the current issue of the United European Gastroenterology Journal, Uchida et al. assessed the risk of developing IBD in individuals with histopathologic-proven diagnosis of EoE. 6 Between 1990 and 2017, using a Swedish nationwide histopathologic database, the authors identified 1587 individuals with EoE. Each of them was matched to five general population reference individuals according to age, sex, and year of diagnosis of EoE, with a total of 7808 individuals. Individuals with EoE were excluded if they had a prior diagnosis of IBD and the follow-up ended in December 2019. Of note, individuals with EoE underwent more endoscopies during follow-up than the reference individuals. Overall, 16 EoE individuals(0.01%) and 21 reference individuals (0.003%), were diagnosed with IBD during follow-up. The risk of developing IBD was 3.5-fold higher in the EoE group compared to matched individuals from the general population. In subgroup analyses, individuals with EoE were at higher risk of developing later Crohn's disease (CD), but not ulcerative colitis (UC). These results suggest that only CD could be associated with EoE. Additionally, the risk of being diagnosed with EoE was 15 times higher in patients with IBD compared to the general population, suggesting a bidirectional association. Some limitations need to be acknowledged. First, surveillance bias could occur as individuals with EoE were more likely to have upper GI endoscopies during follow-up that could identify lesions related to CD. Patients with EoE are more prone to being followed by GI doctors and so undergo subsequent GI endoscopies. Second, important confounding factors are not collected in the Swedish administrative healthcare databases, notably smoking or medications such as proton pump inhibitors, and residual confounding cannot be excluded.

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Host–Microbiota Interactions in the Esophagus During Homeostasis and Allergic Inflammation

Cited by 32 publications

References 63 publications

Single-cell RNA-Seq of human esophageal epithelium in homeostasis and allergic inflammation

Single-cell RNA-Seq of human esophageal epithelium in homeostasis and allergic inflammation

Maternal and Infant Antibiotic and Acid Suppressant Use and Risk of Eosinophilic Esophagitis

Inflammatory bowel diseases and eosinophilic oesophagitis: Two overlapping disorders?

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