Al-Momani Hafez, Nelson Andrew, Al Balawi Hadeel, Al Balawi Dua'a, Aolymat Iman, Khasawneh Ashraf I, Tabl Hala, Alsheikh Ayman, Zueter AbdelRahman M, Pearson Jeffrey, Ward Christopher
Department of Microbiology, Pathology and Forensic Medicine, Faculty of Medicine, The Hashemite University, P.O box 330127, Zarqa, 13133, Jordan.
Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Northumberland Building, Newcastle Upon Tyne, NE1 8ST, United Kingdom.
Sci Rep. 2025 Jan 13;15(1):1811. doi: 10.1038/s41598-025-85806-5.
SARS-CoV-2 is the viral pathogen responsible for COVID-19. Although morbidity and mortality frequently occur as a result of lung disease, the gastrointestinal (GI) tract is recognized as a primary location for SARS-CoV-2. Connections and interactions between the microbiome of the gut and respiratory system have been linked with viral infections via what has been referred to as the 'gut-lung axis' with potential aerodigestive communication in health and disease. This research explored the relationship between the microbiomes of the upper respiratory and GI tracts in patients with COVID-19 and examined Extraesophageal reflux (EOR), a mechanism which could contribute to dysregulated communication between the GI and respiratory tract (as identified in COVID-19). 97 patients with a laboratory diagnosis of COVID-19 infection, and 50 age-matched controls were recruited and stool, saliva and sputum were obtained from each participant. ELISA Pepsin tests and Reflux Symptom Index scores (RSI) were conducted for EOR assessment. DNA sequencing of the V4 region of the 16 S rRNA gene was performed for microbiome analysis. No differences were observed between the fecal microbiome's alpha and Shannon diversity indices; however, a distinct microbial composition was observed in COVID-19 patients (when compared to the controls). The respiratory microbiota from individuals with COVID-19 demonstrated a statistically significant reduction in Shannon diversity and bacterial richness alongside an overall reduction in the prevalence of organisms from a typical healthy respiratory microbiome. Furthermore, the bacterial richness of the stool and sputum samples was significantly lower among COVID-19 patients admitted to ICU. A significantly higher RSI score and salivary pepsin level were detected among those with COVID-19. The data indicates that COVID-19 is associated with a dysregulation of both the gut and lung microbiome with a more marked perturbation in the lung, particularly among COVID-19 patients who had been admitted to the ICU. The presence of increased RSI scores, combined with elevated levels of Pepsin, suggests that increased micro-aspiration may occur, which is consistent with of under-recognized interactions between the GI and lung microbiomes in COVID-19 patients and requires additional study. Such studies would benefit from the insights provided by biological samples which reflect the continuum of the aerodigestive tract.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）是导致2019冠状病毒病（COVID-19）的病毒病原体。虽然发病和死亡常因肺部疾病所致，但胃肠道被认为是SARS-CoV-2的主要感染部位。肠道微生物群与呼吸系统之间的联系和相互作用，通过所谓的“肠-肺轴”与病毒感染相关联，在健康和疾病状态下可能存在气消化道间的交流。本研究探讨了COVID-19患者上呼吸道和胃肠道微生物群之间的关系，并研究了食管外反流（EOR），这是一种可能导致胃肠道和呼吸道之间通讯失调的机制（在COVID-19中已得到确认）。招募了97例实验室诊断为COVID-19感染的患者和50例年龄匹配的对照者，并从每位参与者处获取粪便、唾液和痰液。进行了ELISA胃蛋白酶检测和反流症状指数评分（RSI）以评估EOR。对16S rRNA基因的V4区域进行DNA测序以进行微生物群分析。在粪便微生物群的α多样性指数和香农多样性指数之间未观察到差异；然而，在COVID-19患者中观察到了独特的微生物组成（与对照组相比）。COVID-19患者的呼吸道微生物群在香农多样性和细菌丰富度方面有统计学显著降低，同时来自典型健康呼吸道微生物群的生物体总体患病率也有所下降。此外，入住重症监护病房（ICU）的COVID-19患者的粪便和痰液样本中的细菌丰富度显著降低。在COVID-19患者中检测到显著更高的RSI评分和唾液胃蛋白酶水平。数据表明，COVID-19与肠道和肺部微生物群的失调有关，肺部的扰动更为明显，尤其是在入住ICU的COVID-19患者中。RSI评分增加以及胃蛋白酶水平升高表明可能发生了更多的微误吸，这与COVID-19患者中胃肠道和肺部微生物群之间未被充分认识的相互作用一致，需要进一步研究。此类研究将受益于反映气消化道连续性的生物样本所提供的见解。
