Characterizing the breast cancer lipidome and its interaction with the tissue microbiota

Abstract

Breast cancer is the most diagnosed cancer amongst women worldwide. We have previously shown that there is a breast microbiota which differs between women who have breast cancer and those who are disease-free. To better understand the local biochemical perturbations occurring with disease and the potential contribution of the breast microbiome, lipid profiling was performed on non-tumor breast tissue collected from 19 healthy women and 42 with breast cancer. Here we identified unique lipid signatures between the two groups with greater amounts of lysophosphatidylcholines and oxidized cholesteryl esters in the tissue from women with breast cancer and lower amounts of ceramides, diacylglycerols, phosphatidylcholines, and phosphatidylethanolamines. By integrating these lipid signatures with the breast bacterial profiles, we observed that Gammaproteobacteria and those from the class Bacillus, were negatively correlated with ceramides, lipids with antiproliferative properties. In the healthy tissues, diacylglyerols were positively associated with Acinetobacter, Lactococcus, Corynebacterium, Prevotella and Streptococcus. These bacterial groups were found to possess the genetic potential to synthesize these lipids. The cause-effect relationships of these observations and their contribution to disease patho-mechanisms warrants further investigation for a disease afflicting millions of women around the world.

The breast tissue microbiome, stroma, immune cells and breast cancer

“…the antigens from Staphylococci) increase adiponectin secretion and decrease resistin secretion in vitro [29] . A recent study evaluated lipid signatures with chromatography and mass spectometry in association with the breast tissue microbiome in samples taken from clinically normal breast tissue from women with cancer or undergoing breast reduction [30] . The investigators found decreased ceramides, lipids with tumor suppressive antiproliferative effects, in tissues from women with breast cancer while in samples from the women without cancer there was increased relative abundance of bacteria genera with the capacity to synthesize these lipids including diacylglycerols, second messengers that drive activation, proliferation, migration, and effector function of both adaptive and innate immune cells.…”

Endometrial microbiota from endometrial cancer and paired pericancer tissues in postmenopausal women: differences and clinical relevance

“…[17][18][19] However, the relationship between endometrial bacteria and EC development is of greater concern than that between gut microbiota and EC development because tissue microbiota may directly affect tumor behavior. 20,21 About tissue microbiota, more enigmas wait to be urgently clarified.…”

The involvement of oncobiosis and bacterial metabolite signaling in metastasis formation in breast cancer

“…Multiple microbial compartments undergo oncobiotic transformation during breast cancer, including breast tissue [55,56], milk ducts [57], the inherent microbiome of the breast carcinoma [54,[58][59][60][61][62][63][64][65][66][67][68][69][70][71][72], the distal gut [51,52,[73][74][75][76][77][78][79][80][81][82][83][84][85][86][87][88][89], and the urinary microbiome [54,90]. However, no differences in the microbiome of the nipple [57,69] and the oral microbiome [54] between healthy individuals and breast cancer patients have been detected.…”

“…Furthermore, the intricate supportive metabolic circuit between cancer cells and non-cancerous stroma cells can facilitate tumor growth and lead to worse clinical outcomes [103][104][105]113]. Giallourou and colleagues [71] showed that breast bacteria interfere with the biosynthesis of ceramide, cholesterol, oxidized cholesteryl esters, diacylglycerol, lysophosphatidylcholine, phosphatidylethanolamines, and phosphatidylcholines to modulate the lipid composition of tumors. Of note, cholesterol and lipid homeostasis also play a role [4,[114][115][116].…”

“…Differences in ER + and ER- breast tumors [ 67 ] 21 female and 2 male BC patients 16S rRNA gene sequencing Compared to normal breast tissue, the abundance of Proteobacteria increased in tumor tissue [ 69 ] 95–105 FFPE samples for each BC subtype, 86 controls Pathochip Large set of viruses, parasites, and fungi were detected in FFPE sections of breast cancer. The least of these were detected in TNBC cases [ 70 ] 16 healthy controls, 32 breast cancer patients 16S rRNA gene sequencing The abundance of Corynebacterium, Prevotella, and Gammaproteobacteria (unclassified) decreased, while Acinetobacter increased in BC tissue [ 71 ] Changes to the gut microbiome 48 postmenopausal BC patients (most stages 0–I), vs. 48 control patients 16S rRNA gene sequencing Breast cancer patients had a higher abundance of Clostridium , Faecalibacterium , and Ruminococcus (all Clostridiales ) and a lower abundance of Dorea and Lachnospiraceae Lower number of observed species, Chao1 and PD whole tree indices in breast cancer patients [ 73 ] 30 BC and 36 control patients Classical bacterial culture Fecal bile acid levels were lower in breast cancer patients. Bacterial nuclear dehydrogenating activity increased in breast cancer patients suggesting increases in Clostridia abundance in feces [ 82 ] 18 premenopausal BC patients, 25 premenopausal controls, 44 postmenopausal BC patients, 46 postmenopausal healthy controls Comprehensive shotgun sequencing Species number, chao1, and JSD values were higher in postmenopausal cancer patients than in controls.…”