Gut Microbiota In Women Research Articles

Abstract 2830: Breast cancer and the human oral and gut microbiomes

Abstract The human body harbors ten times more bacterial cells than human cells - a stunning figure that suggests a likely dynamic between our bodies and the bacteria we carry, both in health and disease. In this study, we characterized and compared the gut and oral microbiota from women with invasive breast cancer, women with ductal carcinoma in situ (DCIS), and healthy women. Samples were collected prior to any systemic therapy to avoid therapy-associated effects on the microbiomes studied. Kits for collecting oral and stool swab samples were distributed to patients for self-collection. DNA was isolated from these samples and bacterial 16S rRNA was PCR amplified and sequenced. Based on the sequencing results, bacterial taxa present in the samples were enumerated. The gut microbiota of women with breast cancer demonstrated significantly lower alpha-diversity compared to the gut microbiomes of healthy women. In contrast, there was no difference in gut microbiota alpha-diversity of women with DCIS compared to healthy women. There were no differences in alpha-diversity of the oral microbiota between any of the cohorts. Discriminant analysis of principal components (DAPC) at the genus level of both the gut and oral microbiota demonstrated distinct clustering of the DCIS, breast cancer, and healthy cohorts. LEfSe analyses were performed to detect differences in relative abundance of bacterial taxa across the gut and oral samples. The genus Bacteroides was significantly enriched in breast cancer compared to healthy samples, as were the related taxa Bacteroidetes (phylum), Bacteroidia (class), Bacteroidales (order), and Bacteroidaceae (family). The genera Fusicatenibacter and Butyrivibrio, both from the phylum Firmicutes, class Clostridia, order Clostridiales, family Lachnospiraceae, were more abundant in the healthy cohort. Only 2 genera, Fusicatenibacter and Clostridium were differentially abundant between the DCIS and healthy gut samples, both being enriched in the healthy samples. Numerous taxa in the oral microbiota were found to be differentially abundant between cohorts. In particular, 7 genera (Bacteroides, Blautia, Faecalibacterium, Roseburia, Pseudobutyrivibrio, Anaerostipes, and Subdoligranulum) were all significantly enriched in the healthy oral samples compared to the DCIS and breast cancer oral samples. To determine whether the taxonomic differences we observed between the cohorts’ gut and oral microbiota corresponded to functional differences, we performed a predictive functional analysis using Piphillin which identified 35 KEGG pathways differentially present in the gut microbiota and 8 pathways differentially present in the oral samples. Understanding how gut and oral microbiomes relate to breast cancer may open up new opportunities for the development of novel markers for early detection (or markers of susceptibility) as well as new strategies for prevention and/or treatment. Citation Format: Michael J. Campbell, Emma McCune, Breanna Johnson, Tess O'Meara, Diane Heditsian, Susie Brain, Laura Esserman. Breast cancer and the human oral and gut microbiomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2830.

Early-Onset Preeclampsia Is Associated With Gut Microbial Alterations in Antepartum and Postpartum Women.

Background: Imbalances in gut microbiota composition are linked to hypertension, host metabolic abnormalities, systemic inflammation, and other conditions. In the present study, we examined the changes of gut microbiota in women with early-onset preeclampsia (PE) and in normotensive, uncomplicated pregnant women during late pregnancy and at 1 and 6 weeks postpartum.Methods: Gut microbiota profiles of women with PE and healthy pregnant women in the third trimester and at 1 and 6 weeks postpartum were assessed by 16S rRNA gene amplicon sequencing. Plasma levels of interleukin-6 (IL-6), intestinal fatty acid-binding protein (I-FABP), zonulin, and lipopolysaccharide (LPS) were measured in the third trimesters.Results: At the genus level, 8 bacterial genera were significantly enriched in the antepartum samples of PE patients compared to healthy controls, of which Blautia, Ruminococcus2, Bilophila, and Fusobacterium represented the major variances in PE microbiomes. Conversely, 5 genera, including Faecalibacterium, Gemmiger, Akkermansia, Dialister, and Methanobrevibacter, were significantly depleted in antepartum PE samples. Maternal blood pressure and liver enzyme levels were positively correlated to the PE-enriched genera such as Anaerococcus, Ruminococcus2, Oribacterium, and Bilophila, while the fetal features (e.g., Apgar score and newborn birth weight) were positively correlated with PE-depleted genera and negatively correlated with PE-enriched genera. Moreover, maternal blood IL-6 level was positively associated with gut Bilophila and Oribacterium, whereas LPS level was negatively associated with Akkermansia. In terms of postpartum women, both the gut microbial composition and the PE-associated microbial alterations were highly consistent with those of the antepartum women.Conclusion: PE diagnosed in the third trimester of pregnancy is associated with a disrupted gut microbiota composition compared with uncomplicated pregnant women, which are associated with maternal clinical features (blood pressure level and liver dysfunction) and newborn birth weight. Moreover, these antepartum alterations in gut microbiota persisted 6 weeks postpartum.

71. Altered composition of the gut microbiota in women who develop hypertensive disorders of pregnancy

Introduction Metabolites released by the gut microbiota affect host physiology. Hypertension is associated with altered composition of the gut microbiota. In early pregnancy, the abundance of bacteria producing the short-chain fatty acid butyrate, is negatively correlated with blood pressure in the mother. Butyrate may affect blood pressure through affecting GPR41 and 43 signalling. It is unclear if gut microbiota composition is altered in women who develop hypertensive disorders of pregnancy (HDP). Objective To compare the composition of the gut microbiota at 28 weeks gestation between women who do and do not develop HDP later in pregnancy. Methods Gut microbiota composition was assessed by 16S rRNA sequencing in faecal samples obtained from participants in the Study of Probiotics IN gestational diabetes (SPRING) RCT at 28 weeks gestation. In SPRING, women were randomised to a probiotics or placebo intervention from 16 weeks gestation. Gut microbiota composition was assessed using the QIIME and Calypso software suites. The composition was compared between women with future HDP (N = 32) and those who remained normotensive (N = 182). Results Rates of HDP and overall gut microbiota composition were similar between women randomised to probiotics (7.1%, N = 15) and placebo (8.0%, N = 17; P = 0.85) and the treatment groups were therefore pooled. At 28 weeks gestation, the women with future HDP already had significantly higher systolic and diastolic blood pressures than those who remained normotensive. Women with future HDP had higher abundance of Collinsella aerofasciens, Ruminococcus gnavus, Blautia producta and Bifidobacterium longum. They had lower abundance of Faecalibacterium prausnitzii, Coprococcus eutactus and Roseburia faecis, which are all known butyrate producers. Discussion The gut microbiota of women with future HDP has lower abundance of butyrate-producing bacteria at 28 weeks gestation prior to the development of overt hypertension. This may suggest that lower abundance of short-chain fatty acid producers predisposes to the development of HDP.

Gut microbiota, dietary intakes and intestinal permeability reflected by serum zonulin in women

PurposeIncreased gut permeability causes the trespass of antigens into the blood stream which leads to inflammation. Gut permeability reflected by serum zonulin and diversity of the gut microbiome were investigated in this cross-sectional study involving female study participants with different activity and BMI levels.Methods102 women were included (BMI range 13.24–46.89 kg m−2): Anorexia nervosa patients (n = 17), athletes (n = 20), normal weight (n = 25), overweight (n = 21) and obese women (n = 19). DNA was extracted from stool samples and subjected to 16S rRNA gene analysis (V1–V2). Quantitative Insights Into Microbial Ecology (QIIME) was used to analyze data. Zonulin was measured with ELISA. Nutrient intake was assessed by repeated 24-h dietary recalls. We used the median of serum zonulin concentration to divide our participants into a “high-zonulin” (> 53.64 ng/ml) and “low-zonulin” (< 53.64 ng/ml) group.ResultsThe alpha-diversity (Shannon Index, Simpson Index, equitability) and beta-diversity (unweighted and weighted UniFrac distances) of the gut microbiome were not significantly different between the groups. Zonulin concentrations correlated significantly with total calorie-, protein-, carbohydrate-, sodium- and vitamin B12 intake. Linear discriminant analysis effect size (LEfSe) identified Ruminococcaceae (LDA = 4.163, p = 0.003) and Faecalibacterium (LDA = 4.151, p = 0.0002) as significantly more abundant in the low zonulin group.ConclusionButyrate-producing gut bacteria such as Faecalibacteria could decrease gut permeability and lower inflammation. The diversity of the gut microbiota in women does not seem to be correlated with the serum zonulin concentration. Further interventional studies are needed to investigate gut mucosal permeability and the gut microbiome in the context of dietary factors.

Sex differences in NSAID-induced perturbation of human intestinal barrier function and microbiota.

Intestinal barrier function and microbiota are integrally related and play critical roles in maintenance of host physiology. Sex is a key biologic variable for several disorders. Our aim was to determine sex-based differences in response to perturbation and subsequent recovery of intestinal barrier function and microbiota in healthy humans. Twenty-three volunteers underwent duodenal biopsies, mucosal impedance, and in vivo permeability measurement. Permeability testing was repeated after administration of indomethacin, then 4 to 6 wk after its discontinuation. Duodenal and fecal microbiota composition was determined using 16S rRNA amplicon sequencing. Healthy women had lower intestinal permeability and higher duodenal and fecal microbial diversity than healthy men. Intestinal permeability increases after indomethacin administration in both sexes. However, only women demonstrated decreased fecal microbial diversity, including an increase in Prevotella abundance, after indomethacin administration. Duodenal microbiota composition did not show sex-specific changes. The increase in permeability and microbiota changes normalized after discontinuation of indomethacin. In summary, women have lower intestinal permeability and higher microbial diversity. Intestinal permeability is sensitive to perturbation but recovers to baseline. Gut microbiota in women is sensitive to perturbation but appears to be more stable in men. Sex-based differences in intestinal barrier function and microbiome should be considered in future studies.-Edogawa, S., Peters, S. A., Jenkins, G. D., Gurunathan, S. V., Sundt, W. J., Johnson, S., Lennon, R. J., Dyer, R. B., Camilleri, M., Kashyap, P. C., Farrugia, G., Chen, J., Singh, R. J., Grover, M. Sex differences in NSAID-induced perturbation of human intestinal barrier function and microbiota.

Distinct composition of gut microbiota during pregnancy in overweight and normal-weight women

Background: Results of experimental studies suggest that deviations in gut microbiota composition predispose to excessive energy storage and obesity. The mother influences the original inoculum and the development of infant microbiota, which in turn is associated with later weight gain.Objective: We characterized the gut microbiota in women according to their body mass index (BMI) and the effect of weight gain over pregnancy on the composition of microbiota before delivery.Design: Overweight women (n = 18) were selected according to their prepregnancy BMI from a prospective follow-up study. Normal-weight women (n = 36) were selected as controls in consecutive order of recruitment. Excessive weight gain during pregnancy was defined as >16.0 kg for normal-weight and >11.5 kg for overweight states according to Institute of Medicine recommendations. The composition of gut microbiota was analyzed by fluorescent in situ hybridization coupled with flow cytometry (FCM-FISH) and by quantitative real-time polymerase chain reaction (qPCR).Results:Bacteroides and Staphylococcus were significantly higher in the overweight state than in normal-weight women as assessed by FCM-FISH and qPCR. Mother's weight and BMI before pregnancy correlated with higher concentrations of Bacteroides, Clostridium, and Staphylococcus. Microbial counts increased from the first to third trimester of pregnancy. High Bacteroides concentrations were associated with excessive weight gain over pregnancy (P = 0.014).Conclusions: Gut microbiota composition and weight are linked, and mother's weight gain is affected by microbiota. Microbiota modification before and during pregnancy may offer new directions for preventive and therapeutic applications in reducing the risk of overweight and obesity.