Laryngopharyngeal reflux disease (LPRD) is a commonly encountered extraesophageal reflux condition in otolaryngology practice. Its prevalence is steadily increasing, with an onset observed in progressively younger populations. The clinical manifestations of LPRD are notably nonspecific, often resulting in misdiagnosis. In its more severe forms, LPRD can lead to a range of complications, and some studies have suggested a possible association with laryngeal cancer, although the evidence remains controversial. The gut microbiota, often referred to as the human “second genome,” plays crucial roles in host metabolism, immune regulation, and the maintenance of mucosal barrier integrity. As a result, gut dysbiosis is closely linked to a wide array of systemic disorders.Recent evidence has demonstrated that patients with LPRD exhibit reduced gut microbial diversity alongside imbalances in the relative abundance of specific bacterial taxa. In parallel, proton pump inhibitors (PPIs), the first-line pharmacotherapy for LPRD, can further exacerbate gut dysbiosis and elevate the risk of small intestinal bacterial overgrowth (SIBO), thereby perpetuating a vicious cycle of reflux deterioration. This review synthesizes the latest advances in the mechanistic pathways through which gut dysbiosis contributes to LPRD, with the aim of elucidating its pathogenesis and inspiring novel therapeutic strategies.
ObjectiveTo explore the potential association of fecal microbiota transplantation (FMT) with gastrointestinal symptoms and intestinal dysbiosis in patients recovering from severe pneumonia.MethodsA total of 15 adult patients with confirmed severe pneumonia were enrolled. One patient died and two were excluded from clinical analysis because timely blood routine data were unavailable; therefore, 12 patients were included in the clinical evaluation. FMT was administered once daily for six consecutive days via a colonoscopically placed catheter at the cecum. Clinical evaluations and blood samples were conducted at baseline and one week post-treatment. Fecal samples from six patients were collected at baseline and six months post-FMT and analyzed using metagenomic sequencing.ResultsAfter FMT treated for one week, five out of 12 patients reported symptom improvement, and nine out of 10 who had experienced fever before showed resolution within two weeks following treatment. Analysis of the gut microbiota (Beta diversity) revealed that the gut microbiota composition of recipients converged toward that of their donors post-FMT, which suggests that the improvement in symptoms might be related to FMT treatment. Specifically, at the phylum level, the relative abundance of Proteobacteria and Actinobacteria decreased, whereas Firmicutes and Bacteroidetes increased after FMT compared to baseline. At the genus level, a significant enrichment of common commensal bacteria (e.g. Phocaeicola, Parabacteroides, Lachnospira, and Phascolarctobacterium) was observed after FMT, while pathogenic genera such as Vibrio, Streptococcus, and Enterobacter were significantly reduced. Further analysis of the functions of the microbial community revealed a significant shift in microbial functional profiles toward the donor state after FMT, marked by the upregulation of core metabolic and cellular processes and the downregulation of pathways linked to infections, which collectively indicate a functional restoration of the gut microbiome.ConclusionsThis study suggests that FMT may be closely related to the improvement of symptoms in patients with severe pneumonia and the restoration of intestinal microbial homeostasis. These findings suggest that FMT may be associated with therapeutic benefit and could represent a feasible rehabilitative strategy for individuals recovering from severe pneumonia.
BackgroundSpinal tuberculosis is a severe form of extrapulmonary tuberculosis that often results in delayed diagnosis and irreversible neurological complications. Xpert MTB/RIF and Xpert MTB/RIF Ultra have been developed as rapid molecular diagnostic tools; however, their diagnostic performance in spinal tuberculosis remains uncertain, particularly across different reference standards.ObjectiveTo systematically evaluate the diagnostic accuracy of Xpert-based assays for spinal tuberculosis and assess the influence of different reference standards on pooled diagnostic estimates.MethodsA systematic search of PubMed, Embase, Web of Science, and the Cochrane Library was performed from database inception to June 2026. Studies evaluating Xpert MTB/RIF or Xpert MTB/RIF Ultra in patients with suspected spinal tuberculosis and providing sufficient data to construct 2×2 diagnostic tables were included. Pooled sensitivity, specificity, likelihood ratios, and diagnostic odds ratios were estimated using a bivariate random-effects model. Hierarchical summary receiver operating characteristic (HSROC) curves were generated. The primary analysis included studies using composite or clinical reference standards, whereas mycobacterial culture alone was evaluated in a separate sensitivity analysis.ResultsTwelve studies were included in the quantitative synthesis. In the primary analysis based on composite or clinical reference standards, the pooled sensitivity and specificity of Xpert-based assays were 0.77 (95% CI: 0.66–0.86) and 1.00 (95% CI: 0.99–1.00), respectively. The pooled positive and negative likelihood ratios were 43.86 (95% CI: 23.65–81.36) and 0.24 (95% CI: 0.15–0.37), respectively, with a diagnostic odds ratio of 213.28 (95% CI: 89.30–509.42). In the sensitivity analysis using mycobacterial culture as the reference standard, pooled sensitivity increased to 0.94 (95% CI: 0.88–0.98), whereas specificity decreased to 0.62 (95% CI: 0.44–0.78). Only one included study evaluated Xpert MTB/RIF Ultra, limiting conclusions regarding its comparative performance.ConclusionXpert-based assays demonstrate high diagnostic accuracy for spinal tuberculosis, particularly strong confirmatory capability due to high specificity. However, negative results alone are insufficient to exclude disease. The choice of reference standard substantially influences pooled diagnostic estimates, highlighting the importance of interpreting Xpert results together with clinical, radiological, microbiological, and histopathological findings.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420261427181, identifier CRD420261427181.
BackgroundOral squamous cell carcinoma (OSCC) arises at a microbially exposed mucosa, but the relationship between tumor transcriptional programs and host responses to Candida albicans is uncertain. We sought direction-consistent genes shared with short-term C. albicans stimulation and assessed their diagnostic, cellular, pathway, and tissue contexts.MethodsWe directionally integrated four paired C. albicans-stimulated/control oral-epithelial experiments (GSE56091) with 40 paired OSCC/adjacent tissues (GSE37991). Four machine-learning methods prioritized candidates, and independent bulk validation used 167 OSCCs and 45 controls (GSE30784). An exploratory ridge score was fixed in the discovery cohort and applied to the external cohort. Cellular localization and state were examined in paired single-cell profiles from seven patients (GSE198315) and an external oral-cavity subset of 10 carcinomas and three normal-mucosa samples (GSE181919). Qualitative PAS and IHC assessment used archival oral tissues from three groups, with four cases per group.ResultsCandida stimulation yielded 508 exploratory differentially expressed genes, and OSCC yielded 1,850; 26 of 35 overlapping genes changed concordantly. The four-method intersection comprised MMP10, CA9, and STC2; external single-gene AUCs were 0.968, 0.714, and 0.907, respectively. The three-gene score achieved an external AUC of 0.959 (95% CI 0.935-0.983), but at the discovery-derived cutoff sensitivity was 0.605 and specificity was 1.000; calibration was poor, and discrimination did not exceed MMP10 alone (DeLong P = 0.365). In GSE198315, paired epithelial pseudobulk supported MMP10 and CA9 under prespecified targeted three-gene correction (FDR = 0.0455 for both), whereas STC2 was directional but nonsignificant (FDR = 0.0665). Genome-wide FDR was approximately 0.892 for each gene, so the single-cell findings support localization and directional consistency rather than definitive genome-wide differential expression. The q95 calls showed modest overlap with CopyKAT and inferCNV (Jaccard=0.141 and 0.254, respectively). MMP10 and CA9 showed stronger pooled descriptive localization than STC2; CA9 remained hypoxia-associated. Fungal-element-compatible PAS staining provided morphological context but could neither identify species nor quantify burden.ConclusionsMMP10 and CA9 had the strongest multi-level support as direction-consistent Candida-responsive OSCC candidates, while STC2 remains exploratory. The three-gene combination is not yet a calibrated clinical model, and the 26-gene overlap defines a shared host-response pattern rather than evidence that C. albicans causes the OSCC transcriptional state.
