Probiotics for the Treatment of Docetaxel-Related Weight Gain of Breast Cancer Patients—A Single-Center, Randomized, Double-Blind, and Placebo-Controlled Trial

Abstract

Background: Docetaxel is an important chemotherapy-agent for breast cancer treatment. One of its side-effects is weight gain, which increases the all-cause mortality rate. Considering gut microbiota is one important factor for weight regulation, we hypothesized that probiotics could be potentially used to reduce the docetaxel-related weight gain in breast cancer patients.Methods: From 10/8/2018 to 10/17/2019, 100 breast cancer (Stage I-III) patients underwent four cycles of docetaxel-based chemotherapy were enrolled and randomly assigned to receive probiotics (Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis) or placebo (supplementary material of the probiotics capsule) treatment for 84 days with three capsules per time, twice/day. The primary outcome: the changes in body weight and body-fat percentage of the patients were measured by a designated physician using a fat analyzer, and the secondary outcomes: the fasting insulin, plasma glucose, and lipids were directly obtained from the Hospital Information System (HIS); The metabolites were measured using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS); The fecal microbiome was analyzed using bacterial 16S ribosomal RNA (rRNA) gene sequence. All indicators were measured 1 day before the first cycle of docetaxel-based chemotherapy and 21 days after the last cycle of docetaxel-based chemotherapy.Results: Compared with the placebo group, the probiotic group showed significantly smaller changes in body weight (Mean [SD] 0.77 [2.58] vs. 2.70 [3.08], P = 0.03), body-fat percentage (Mean [SD] 0.04 [1.14] vs. 3.86 [11.09], P = 0.02), and low density lipoprotein (LDL) (Mean [SD]−0.05[0.68] vs. 0.39 [0.58], P = 0.002). Moreover, five of the 340 detected plasma metabolites showed significant differences between the two groups. The change of biliverdin dihydrochloride (B = −0.724, P = 0.02) was inverse correlated with weight gain. One strain of the phylum and three strains of the genus were detected to be significantly different between the two groups. Also, the changes of Bacteroides (B = −0.917, P < 0.001) and Anaerostipes (B = −0.894, P < 0.001) were inverse correlated with the change of LDL.Conclusions: Probiotics supplement during docetaxel-based chemotherapy for breast cancer treatment may help to reduce the increase in body weight, body-fat percentage, plasma LDL, and minimize the metabolic changes and gut dysbacteriosis.Clinical Trial Registration:http://www.chictr.org.cn/showproj.aspx?proj=24294, ChiCTR-INQ-17014181.

Bifidobacterium longum Subsp. infantis Promotes IgA Level of Growing Mice in a Strain-Specific and Intestinal Niche-Dependent Manner

“…However, B6MNI was the sole treatment that enhanced IgA in the colon of female mice, while having no effect on IgA synthesis in the jejunum or ileum. This finding may be explained by strain variations and intestinal niches [ 47 ]. Furthermore, B6MNI was isolated from human breastmilk, whereas the remaining seven strains were obtained from the feces of infants.…”

The gut microbiota in breast cancer development and treatment: The good, the bad, and the useful!

“…In addition, probiotic supplementation leads to stabilized body fat, reduced metabolic changes and attenuated gut dysbacteriosis during docetaxel-based chemotherapy of breast cancer patients 111 . More recently, breast cancer patients who have undergone chemotherapy were subjected to a 12-week exercise regime.…”

Gastrointestinal Microbiota and Breast Cancer Chemotherapy Interactions: A Systematic Review

“…Both studies reported no difference in microbial diversity between the two groups. The first study revealed that probiotic administration during docetaxel-based chemotherapy was associated with stable weight, body fat, glucose, total cholesterol, and low-density lipoprotein (LDL) [22].…”

“…Juan et al conducted two randomized controlled trials which aimed to determine differences in fecal microbiota and incidence of side effects between patients who received a probiotic supplement or placebo during chemotherapy [ 21 , 22 ]. Both studies reported no difference in microbial diversity between the two groups.…”

“…Both studies reported no difference in microbial diversity between the two groups. The first study revealed that probiotic administration during docetaxel-based chemotherapy was associated with stable weight, body fat, glucose, total cholesterol, and low-density lipoprotein (LDL) [ 22 ]. The probiotics group had a lower incidence of constipation as well as a higher abundance of Tenericutes and Eubacterium coprostanoligenes .…”