口服与鼻内益生菌用于鼻腔微生物组调节：途径依赖机制与临床意义的比较综述

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中文摘要

背景： 益生菌对鼻腔微生物组的调节可通过口服给药实现，其依赖肠-鼻轴和全身免疫调节；也可通过鼻内滴注实现，提供即时的局部作用。尽管证据不断增多，但尚无关于这些途径的系统比较发表。本叙述性综述综合比较口服与鼻内益生菌策略的临床和机制证据，以指导基于疾病病理生理学和菌株特异性疗效的途径选择。方法：我们评估了随机对照试验、系统综述、荟萃分析和机制研究，这些研究调查了通过任一途径递送益生菌干预用于上呼吸道疾病，包括过敏性鼻炎、慢性鼻窦炎和儿童呼吸道感染。结果：口服益生菌可能通过两种机制对鼻腔产生作用：(i) 通过肠道来源的短链脂肪酸和色氨酸代谢物进行全身免疫调节，这有魏茨曼凝结芽孢杆菌BC99的临床数据以及一项针对儿童常年性过敏性鼻炎的婴儿双歧杆菌CCFM111随机对照试验支持；(ii) 直接的oropharyngeal-to-nasopharyngeal转运，例如一种缓释咀嚼型鼠李糖乳酪杆菌GG制剂在8周后转运至鼻咽部，使用者中占41%，益生菌组和安慰剂组均观察到鼻IL-13下降，且益生菌组症状控制改善。长双歧杆菌和植物乳杆菌组合NVP-1703降低了儿童的2型细胞因子比率。鼻内益生菌，包括芽孢杆菌孢子喷雾和唾液链球菌24SMB/口腔链球菌89a，在涉及儿童急性鼻窦炎和中耳炎、腺样体肥大以及肉芽肿性多血管炎相关慢性鼻窦炎的个别试验中显示出病原体置换和临床获益，尽管后者的组内改善未在组间比较中一致确认。然而，一种多菌株乳杆菌鼻喷雾在季节性过敏性鼻炎的交叉试验中失败，一种蜂蜜来源的乳酸菌喷雾在无鼻息肉的慢性鼻窦炎中未显示获益，强调了菌株-疾病匹配的重要性。结论：途径选择可暂由疾病病理生理学指导：全身性2型驱动的疾病可能倾向于口服免疫调节，而急性局部菌群失调可能倾向于鼻内递送。优先研究包括直接比较试验、基于微生物组的分层和缓释制剂。在此之前，临床决策必须依赖机制合理性和菌株特异性数据。

英文摘要

Probiotic modulation of the nasal microbiome can be achieved through oral administration, which relies on the gut-nose axis and systemic immunomodulation, or direct intranasal instillation, which provides immediate local action. Despite growing evidence, no systematic comparison of these routes has been published. This narrative review synthesizes clinical and mechanistic evidence comparing oral versus intranasal probiotic strategies to inform route selection based on disease pathophysiology and strain-specific efficacy. We evaluated randomized controlled trials, systematic reviews, meta-analyses, and mechanistic studies investigating probiotic interventions delivered via either route for upper respiratory conditions including allergic rhinitis, chronic rhinosinusitis, and pediatric respiratory infections. Orally administered probiotics may exert nasal effects through two mechanisms: (i) systemic immunomodulation via gut-derived short-chain fatty acids and tryptophan metabolites, supported by clinical data for Weizmannia coagulans BC99 and by a randomized controlled trial in children with perennial allergic rhinitis for Bifidobacterium longum subsp. infantis CCFM111; and (ii) direct oropharyngeal-to-nasopharyngeal trafficking, exemplified by a slow-release chewable Lacticaseibacillus rhamnosus GG formulation that trafficked to the nasopharynx in 41% of users after 8 weeks, with a decrease in nasal IL-13 observed in both probiotic and placebo groups, and improved symptom control in the probiotic group. The B. longum and Lactobacillus plantarum combination NVP-1703 reduced type-2 cytokine ratios in children. Intranasal probiotics, including Bacillus spore sprays and Streptococcus salivarius 24SMB/S. oralis 89a, have shown pathogen displacement and clinical benefit in individual trials involving pediatric acute rhinosinusitis and otitis media, adenoid hypertrophy, and granulomatosis with polyangiitis-associated chronic rhinosinusitis, although within-group improvements in the latter were not consistently confirmed in between-group comparisons. However, a multi-strain Lactobacillus nasal spray failed in a crossover trial in seasonal allergic rhinitis, and a lactic acid bacterial spray of honeybee origin showed no benefit in chronic rhinosinusitis without nasal polyps, underscoring the importance of strain-disease matching. Route selection may tentatively be guided by disease pathophysiology: systemic type-2-driven conditions may favor oral immunomodulation, while acute localized dysbiosis may favor intranasal delivery. Priority research includes direct comparative trials, microbiome-based stratification, and sustained-release formulations. Until then, clinical decision-making must rely on mechanistic plausibility and strain-specific data.