Circulating eosinophils associated with responsiveness to COVID-19 vaccine and the disease severity in patients with SARS-CoV-2 omicron variant infection.

OBJECTIVE: This study aimed to investigate the longitudinal circulating eosinophil (EOS) data impacted by the COVID-19 vaccine, the predictive role of circulating EOS in the disease severity, and its association with T cell immunity in patients with SARS-CoV-2 Omicron BA.2 variant infection in Shanghai, China. METHODS: We collected a cohort of 1,157 patients infected with SARS-CoV-2 Omicron/BA.2 variant in Shanghai, China. These patients were diagnosed or admitted between Feb 20, 2022, and May 10, 2022, and were classified as asymptomatic (n = 705), mild (n = 286) and severe (n = 166) groups. We compiled and analyzed data of patients' clinical demographic characteristics, laboratory findings, and clinical outcomes. RESULTS: COVID-19 vaccine reduced the incidence of severe cases. Severe patients were shown to have declined peripheral blood EOS. Both the 2 doses and 3 doses of inactivated COVID-19 vaccines promoted the circulating EOS levels. In particular, the 3rd booster shot of inactivated COVID-19 vaccine was shown to have a sustained promoting effect on circulating EOS. Univariate analysis showed that there was a significant difference in age, underlying comorbidities, EOS, lymphocytes, CRP, CD4, and CD8 T cell counts between the mild and the severe patients. Multivariate logistic regression analysis and ROC curve analysis indicate that circulating EOS (AUC = 0.828, p = 0.025), the combination of EOS and CD4 T cell (AUC = 0.920, p = 0.017) can predict the risk of disease severity in patients with SARS-CoV-2 Omicron BA.2 variant infection. CONCLUSIONS: COVID-19 vaccine promotes circulating EOS and reduces the risk of severe illness, and particularly the 3rd booster dose of COVID-19 vaccine sustainedly promotes EOS. Circulating EOS, along with T cell immunity, may have a predictive value for the disease severity in SARS-CoV-2 Omicron infected patients.

Broad-spectrum antibiotics associated gut microbiome disturbance impairs T cell immunity and promotes lung cancer metastasis: a retrospective study.

BACKGROUND: Gut microbiome has been linked to a regulatory role in cancer progression. However, whether broad-spectrum antibiotics (ATB) associated gut microbiome dysbiosis contributes to an impaired T cell immune function, and ultimately promotes lung cancer metastasis is not well known. METHODS: In this study, a retrospective analysis was performed in a cohort of 263 patients initially diagnosed with non-small cell lung cancer (NSCLC) patients, including the ATB group (patients with broad-spectrum antibiotics treatment) (n = 124), and non-ATB group (n = 139) as control. ATB patients were prescribed ATB for over 5 days within 30 days prior to the collection of blood and fecal specimens and followed surgical treatment or first-line therapy. T cell immune function and metastasis-free survival (MFS) were evaluated between the two groups. Gut microbiota was evaluated by 16S rDNA sequencing. The predictive value of T cell immunity for MFS was evaluated by ROC analysis and Cox regression analysis. RESULTS: Our results suggest that broad-spectrum antibiotics (ATB) impair T cell immune function in patients with either early-stage or advanced NSCLC, which likely contribute to the promotion of lung cancer metastasis. Results of the survival analysis show that metastasis-free survival (MFS) is significantly shorter in the ATB patients than that in the non-ATB patients with stage III NSCLC. The 16S rDNA sequencing shows that ATB administration contributes to a significant dysbiosis of the composition and diversity of gut microbiota. Moreover, ROC analysis results of CD4 (AUC 0.642, p = 0.011), CD8 (AUC was 0.729, p < 0.001), CD16 + 56 + (AUC 0.643, p = 0.003), and the combination of CD4, CD8 and CD16 + 56+ (AUC 0.810, p < 0.001), or Cox regression analysis results of CD4 (HR 0.206, p < 0.001), CD8 (HR 0.555, p = 0.009), which is likely regulated by ATB administration, have significantly predictive values for MFS. CONCLUSION: These results provide evidence of gut microbiome disturbance due to ATB administration is involved in the regulation of T cell immunity, and their predictive value for the tumor metastasis in lung cancer patients. Thus, gut microbiota may serve as a therapeutic target for lung cancer. Consequently, caution should be exercised before the long-term administration of broad-spectrum antibiotics in cancer patients.

Microbiome and spatially resolved metabolomics analysis reveal the anticancer role of gut Akkermansia muciniphila by crosstalk with intratumoral microbiota and reprogramming tumoral metabolism in mice.

Although gut microbiota has been linked to cancer, little is known about the crosstalk between gut- and intratumoral-microbiomes. The goal of this study was to determine whether gut Akkermansia muciniphila (Akk) is involved in the regulation of intratumoral microbiome and metabolic contexture, leading to an anticancer effect on lung cancer. We evaluated the effects of gut endogenous or gavaged exogenous Akk on the tumorigenesis using the Lewis lung cancer mouse model. Feces, blood, and tumor tissue samples were collected for 16S rDNA sequencing. We then conducted spatially resolved metabolomics profiling to discover cancer metabolites in situ directly and to characterize the overall Akk-regulated metabolic features, followed by the correlation analysis of intratumoral bacteria with metabolic network. Our results showed that both endogenous and exogenous gavaged Akk significantly inhibited tumorigenesis. Moreover, we detected increased Akk abundance in blood circulation or tumor tissue by 16S rDNA sequencing in the Akk gavaged mice, compared with the control mice. Of great interest, gavaged Akk may migrate into tumor tissue and influence the composition of intratumoral microbiome. Spatially resolved metabolomics analysis revealed that the gut-derived Akk was able to regulate tumor metabolic pathways, from metabolites to enzymes. Finally, our study identified a significant correlation between the gut Akk-regulated intratumoral bacteria and metabolic network. Together, gut-derived Akk may migrate into blood circulation, and subsequently colonize into lung cancer tissue, which contributes to the suppression of tumorigenesis by influencing tumoral symbiotic microbiome and reprogramming tumoral metabolism, although more studies are needed.