Gut microbiota associated with the mitigation effect of synbiotics on adverse events of neoadjuvant chemotherapy in patients with esophageal cancer: A retrospective exploratory study

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 devel-oping 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.

Automated summary

The study aims to identify the gut microbiota involved in adverse events during neoadjuvant chemotherapy (NAC) and that affect the efficacy of LBG therapy. The results show that higher abundance of Anaerostipes hadrus and Bifidobacterium pseudocatenulatum is associated with lower incidence of febrile neutropenia and severe diarrhoea. Furthermore, LBG+EN therapy is positively correlated with intestinal concentrations of acetic acid and butyric acid.