Abstract：
Introduction. Our synbiotics (Lacticaseibacillus paracasei strain Shirota, Bifidobacterium breve strain Yakult, and galacto-oligosaccharides: LBG) helps mitigate serious adverse events such as febrile neutropenia (FN) and diarrhoea in oesophageal cancer patients receiving neoadjuvant chemotherapy (NAC). Unfortunately, LBG therapy does not benefit all patients.Hypothesis/Gap Statement. Identification of the gut microbiota species involved in adverse events during chemotherapy could help predict the onset of adverse events. Identification of the gut microbiota that influence the efficacy of LBG could also help establish a diagnostic method to identify patients who will respond to LBG before the initiation of therapy.Aim. To identify the gut microbiota involved in adverse events during NAC and that affect the efficacy of LBG therapy.Methodology. This study was ancillary to a parent randomized controlled trial in which 81 oesophageal cancer patients were recruited and administered either prophylactic antibiotics or LBG combined with enteral nutrition (LBG+EN). The study included 73 of 81 patients from whom faecal samples were collected both before and after NAC. The gut microbiota was analysed using 16S rRNA gene amplicon sequencing and compared based on the degree of NAC-associated adverse events. Furthermore, the association between the counts of identified bacteria and adverse events and the mitigation effect of LBG+EN was also analysed.Results. The abundance of Anaerostipes hadrus and Bifidobacterium pseudocatenulatum in patients with no FN or only mild diarrhoea was significantly higher (P<0.05) compared to those with FN or severe diarrhoea. Moreover, subgroup analyses of patients receiving LBG+EN showed that the faecal A. hadrus count before NAC was significantly associated with a risk of developing FN (OR, 0.11; 95 % CI, 0.01-0.60, P=0.019). The faecal A. hadrus count after NAC was positively correlated with intestinal concentrations of acetic acid (P=0.0007) and butyric acid (P=0.00005).Conclusion. Anaerostipes hadrus and B. pseudocatenulatum may be involved in the ameliorating adverse events and can thus be used to identify beforehand patients that would benefit from LBG+EN during NAC. These results also suggest that LBG+EN would be useful in the development of measures to prevent adverse events during NAC.
摘要：
Introduction.我们的合生元（副干酪乳杆菌Shirota，短双歧杆菌菌株Yakult,和低聚半乳糖：LBG）有助于减轻接受新辅助化疗（NAC）的食道癌患者的严重不良事件，如发热性中性粒细胞减少（FN）和腹泻。不幸的是,LBG治疗并不能使所有患者受益。假设/差距声明。在化疗期间与不良事件有关的肠道微生物群物种的鉴定可以帮助预测不良事件的发生。影响LBG功效的肠道微生物群的鉴定也可以帮助建立诊断方法来鉴定在开始治疗之前对LBG有反应的患者。瞄准.确定NAC过程中与不良事件有关的肠道微生物群，并影响LBG治疗的疗效。方法论。这项研究是一项亲本随机对照试验的辅助研究，该试验招募了81名食道癌患者，并给予预防性抗生素或LBG联合肠内营养（LBGEN）。该研究包括81名患者中的73名，这些患者在NAC之前和之后都收集了粪便样本。使用16SrRNA基因扩增子测序分析肠道微生物群,并基于NAC相关不良事件的程度进行比较。此外，本研究还分析了确定的细菌计数和不良事件与LBG+EN缓解效果之间的关联.结果。无FN或仅轻度腹泻的患者的厌氧菌和假双歧杆菌的丰度明显高于FN或严重腹泻的患者（P<0.05）。此外，接受LBG+EN的患者的亚组分析表明，NAC之前的粪便A.hadrus计数与发生FN的风险显着相关（OR，0.11；95%CI，0.01-0.60，P=0.019）。NAC后粪便A.hadrus计数与肠道乙酸（P=0.0007）和丁酸（P=0.00005）的浓度呈正相关。结论。厌氧菌和假性芽孢杆菌可能参与改善不良事件，因此可用于事先识别NAC期间受益于LBGEN的患者。这些结果还表明LBG+EN可用于制定预防NAC期间不良事件的措施。
