Antimicrobial resistance poses a substantial threat to human health. The gut microbiome is considered a reservoir for potential spread of resistance genes from commensals to pathogens, termed the gut resistome. The impact of probiotics, commonly consumed by many in health or in conjunction with the administration of antibiotics, on the gut resistome is elusive. Reanalysis of gut metagenomes from healthy antibiotics-naïve humans supplemented with an 11-probiotic-strain preparation, allowing direct assessment of the gut resistome in situ along the gastrointestinal (GI) tract, demonstrated that probiotics reduce the number of antibiotic resistance genes exclusively in the gut of colonization-permissive individuals. In mice and in a separate cohort of humans, a course of antibiotics resulted in expansion of the lower GI tract resistome, which was mitigated by autologous faecal microbiome transplantation or during spontaneous recovery. In contrast, probiotics further exacerbated resistome expansion in the GI mucosa by supporting the bloom of strains carrying vancomycin resistance genes but not resistance genes encoded by the probiotic strains. Importantly, the aforementioned effects were not reflected in stool samples, highlighting the importance of direct sampling to analyse the effect of probiotics and antibiotics on the gut resistome. Analysing antibiotic resistance gene content in additional published clinical trials with probiotics further highlighted the importance of person-specific metagenomics-based profiling of the gut resistome using direct sampling. Collectively, these findings suggest opposing person-specific and antibiotic-dependent effects of probiotics on the resistome, whose contribution to the spread of antimicrobial resistance genes along the human GI tract merit further studies.

抗菌素耐药性对人类健康构成重大威胁。肠道微生物组被认为是抗性基因从共生体传播到病原体的潜在储存库，称为肠道抗性组。益生菌（通常被许多健康人​​士食用或与抗生素一起使用）对肠道抵抗组的影响是难以捉摸的。对未使用过抗生素的健康人肠道宏基因组进行再分析，并辅以 11 种益生菌菌株制剂，从而可以直接评估沿胃肠道 (GI) 道的原位肠道抗性基因组，结果表明益生菌仅可减少抗生素抗性基因的数量。允许殖民化的个体的肠道。在小鼠和另一组人类中，一个疗程的抗生素导致下消化道抵抗组的扩大，自体粪便微生物组移植或自发恢复期间可减轻这种情况。相比之下，益生菌通过支持携带万古霉素抗性基因但不携带益生菌菌株编码的抗性基因的菌株大量繁殖，进一步加剧了胃肠道粘膜中的耐药性扩增。重要的是，上述影响并未反映在粪便样本中，这凸显了直接取样分析益生菌和抗生素对肠道抗性组影响的重要性。在其他已发表的益生菌临床试验中分析抗生素抗性基因含量进一步强调了使用直接采样对肠道抗性组进行基于人特异性宏基因组分析的重要性。集体，