Abstract P4-13-03: Changes in the gut microbiome of post-menopausal women 2 weeks after initiating a structured weight loss intervention
Authors: CJ Fabian, BF Kimler, S Umar, I Ahmed, CA Befort, JL Nydegger, AL Kreutzjans, KR Powers, JR Klemp, KR Spaeth, DK Sullivan
Journal: Cancer Research (2017)

Abstract Background Change in the relative composition of the gut microbiome at the phyla level, particularly decreases in Bacteroidetes and increases in Firmicutes species, has been associated with both obesity and increased risk for breast cancer. It is unclear how rapidly the microbiome changes in response to a reduced calorie and fat diet during a weight loss intervention. As a planned sub-study of a clinical trial with a structured behavioral weight loss intervention with randomization to high dose omega-3 fatty acids or placebo (NCT02101970; clinical trials.gov), we evaluated changes in the gut microbiome after 2 weeks of dietary intervention. Methods 46 post-menopausal women at increased risk for breast cancer with a BMI &amp;gt; 27 kg/m2 had a baseline 3 day food record, DXA, and blood and breast tissue sampling for biomarkers. They were then started on a reduced fat and calorie diet (~1200 kcal/day from 2 portion-controlled entrees, 3 low calorie high protein shakes, and 5 servings of fruits/vegetables daily), recommendation to exercise 225 minutes per week, and a weekly behavioral intervention. Fecal samples were collected at baseline, after 2 weeks of diet but prior to study agent, and after 6 months of weight loss intervention. Stool samples were stored at -20°C until brought to the clinic, and then at -80°C until DNA extraction. Bacterial taxonomic classification was performed using real-time PCR and 16S pyrosequencing using specific 16S rRNA primers. Baseline Healthy Eating Index (HEI) was calculated from the 3 day food record; fruit and vegetable servings were obtained from weekly food logs. Results 42 women completed the 6 month weight loss intervention. At baseline, median BMI was 31.0 kg/m2 and HEI was 58 (range 28-90) with 12 and 23 servings of fruits and vegetables per week. Median relative weight loss at 6 months was -11.9 % (0 to -22.7 %). When dichotomized to relative losses of &amp;lt;10% vs &amp;gt;10% (which we have previously shown to be associated with significant improvement in blood and breast tissue risk biomarkers [Fabian Cancer Prev Res 2013]), women with 6 month &amp;gt;10% loss had favorable change in the two major stool phyla at 2 weeks with a median 10% increase for Bacteroidetes and 8% decrease for Firmicutes. Conversely, women with &amp;lt;10% loss showed a decrease (median -11%) in Bacteroidetes and an increase (median 16%) for Firmicutes. Fruit and vegetable consumption also differed between the weight loss groups. The &amp;gt;10% loss group had higher baseline consumption of vegetables and continued this after starting the diet. The more adherent a woman was to dietary recommendations in the first weeks of dietary intervention, the more likely she was to lose &amp;gt;10% weight by 6 months. Conclusions Favorable modulation of the gut microbiome early in a weight loss intervention is associated with subsequent substantial weight loss. Microbiome assessment after 6 months of weight loss intervention is in progress. Supported by a grant from the Breast Cancer Research Foundation and pilot funds from National Cancer Institute Cancer Center Support Grant P30 CA168524. Citation Format: Fabian CJ, Kimler BF, Umar S, Ahmed I, Befort CA, Nydegger JL, Kreutzjans AL, Powers KR, Klemp JR, Spaeth KR, Sullivan DK. Changes in the gut microbiome of post-menopausal women 2 weeks after initiating a structured weight loss intervention [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-13-03.