The intestinal microbiome, weight and metabolic changes in women treated by adjuvant chemotherapy for breast and gynecological malignancies.

Adjuvant chemotherapy induces weight gain, glucose intolerance and hypertension in a fraction of women. The mechanisms underlying these events have not been defined. This study assessed the association between the microbiome and weight gain in patients treated with adjuvant chemotherapy for breast and gynecological cancers. Methods: patients were recruited before starting adjuvant therapy. Weight and height were measured before treatment and 4-6 weeks after treatment completion. Weight gain was defined as an increase of 3% or more in body weight. A stool sample was collected before treatment and 16S rRNA gene sequencing was performed. Data regarding oncological therapy, menopausal status and antibiotic use was prospectively collected. Patients were excluded if they were treated by antibiotics during the study. Results: thirty three patients were recruited, of them 9 gained 3.5 - 10.6 percent of baseline weight. The pretreatment microbiome of women who gained weight following treatment was significantly different in diversity and taxonomy from that of control women. Fecal microbiota transplantation from patients that gained weight induced metabolic changes in germ free mice compared to mice transplanted with feces from the control women. Conclusion: The microbiome is predictive of weight gain following adjuvant chemotherapy and induces adverse metabolic changes in germ free mice, suggesting it contributes to adverse metabolic changes seen in patients. Confirmation of these results in a larger patient cohort is warranted.