Gut Microbiota Characteristics Are Associated With Severity of Acute Radiation-Induced Esophagitis

Abstract

BackgroundAcute radiation-induced esophagitis (ARIE) is one of the most debilitating complications in patients who receive thoracic radiotherapy, especially those with esophageal cancer (EC). There is little known about the impact of the characteristics of gut microbiota on the initiation and severity of ARIE.Materials and MethodsGut microbiota samples of EC patients undergoing radiotherapy (n = 7) or concurrent chemoradiotherapy (n = 42) were collected at the start, middle, and end of the radiotherapy regimen. Assessment of patient-reported ARIE was also performed. Based on 16S rRNA gene sequencing, changes of the gut microbial community during the treatment regimen and correlations of the gut microbiota characteristics with the severity of ARIE were investigated.ResultsThere were significant associations of several properties of the gut microbiota with the severity of ARIE. The relative abundance of several genera in the phylum Proteobacteria increased significantly as mucositis severity increased. The predominant genera had characteristic changes during the treatment regimen, such as an increase of opportunistic pathogenic bacteria including Streptococcus. Patients with severe ARIE had significantly lower alpha diversity and a higher abundance of Fusobacterium before radiotherapy, but patients with mild ARIE were enriched in Klebsiella, Roseburia, Veillonella, Prevotella_9, Megasphaera, and Ruminococcus_2. A model combining these genera had the best performance in prediction of severe ARIE (area under the curve: 0.907).ConclusionThe characteristics of gut microbiota before radiotherapy were associated with subsequent ARIE severity. Microbiota-based strategies have potential use for the early prediction of subsequent ARIE and for the selection of interventions that may prevent severe ARIE.

Salivary microbiome is associated with the response to chemoradiotherapy in initially inoperable patients with esophageal squamous cell carcinoma

“…Oral microorganisms can cause esophageal cancer by inducing mild chronic inflammation and distal esophageal cancer [ 24 ]. The characteristics of the gut microbiome affect the severity of acute radiation-induced esophagitis [ 25 ]. Interestingly, the microbiome was more abundant in patients with leukemia undergoing radiotherapy with milder gastrointestinal dysfunction.…”

“…Dendritic cell antigen presentation was modulated by the gut microbiota via a radiotherapy-induced antitumor immune response (CD8+). Vancomycin potentiated the radiotherapy-induced antitumor immune response and tumor growth inhibition dependent on cytolytic CD8+ T cell/IFNγ elicitation and the abscopal effect [ 25 , 51 ].…”

Application of Mendelian randomization to assess host gene–gut microbiota correlations in patients with esophageal cancer

“…The genus Veillonella includes gram-negative, anaerobic, non-motile, and non-spore-forming coccus bacteria ( Djais et al, 2019 ). Veillonella is strongly associated with the development of several diseases, and has been found to promote the proliferation of lung adenocarcinoma ( Zeng et al, 2023 ), whilst Veillonella activates macrophages to promote inflammatory responses via the LPS-TLR4 pathway ( Zhan et al, 2022 ), for example, Veillonella correlated with the severity of radiation esophagitis ( Lin et al, 2022 ), and inflammation is one of the factors leading to esophageal cancer, suggesting that Veillonella may indirectly contribute to esophageal carcinogenesis through inflammation. In our study, only the genus Veillonella positively correlated with ESCA.…”

“…Further, significant variations have been reported in the composition and abundance of fecal microorganisms between patients with ESCA and healthy controls. Notably, these differences are closely correlated with the severity of the disease, suggesting that the gut microbiota may play a significant role in the development of ESCA ( Li et al, 2022 ; Lin et al, 2022 ). Moreover, gut microbiota can alter genome-wide methylation levels in ESCA, which may be one of the mechanisms influencing the malignant behavior of ESCA cells ( Baba et al, 2023 ).…”

Gut microbiota, human blood metabolites and esophageal cancer: a Mendelian randomization study

“…An increasing corpus of studies has demonstrated the intricate relationships between ESCA and the human gut ora in recent years [18][19][20][21]. The composition and abundance of fecal microorganisms in ESCA patients are closely related to the severity of the disease [22]. In addition, the genome-wide methylation level of ESCA can be regulated by the gut microbiota, which affects the occurrence, development, and metastasis of ESCA.…”