scholarly journals Comparison of the Gut Microbiota in Patients with Benign and Malignant Breast Tumors: A Pilot Study

2021 ◽  
Vol 17 ◽  
pp. 117693432110575
Author(s):  
Peidong Yang ◽  
Zhitang Wang ◽  
Qingqin Peng ◽  
Weibin Lian ◽  
Debo Chen

The microbiome plays diverse roles in many diseases and can potentially contribute to cancer development. Breast cancer is the most commonly diagnosed cancer in women worldwide. Thus, we investigated whether the gut microbiota differs between patients with breast carcinoma and those with benign tumors. The DNA of the fecal microbiota community was detected by Illumina sequencing and the taxonomy of 16S rRNA genes. The α-diversity and β-diversity analyses were used to determine richness and evenness of the gut microbiota. Gene function prediction of the microbiota in patients with benign and malignant carcinoma was performed using PICRUSt. There was no significant difference in the α-diversity between patients with benign and malignant tumors ( P = 3.15e−1 for the Chao index and P = 3.1e−1 for the ACE index). The microbiota composition was different between the 2 groups, although no statistical difference was observed in β-diversity. Of the 31 different genera compared between the 2 groups, level of only Citrobacter was significantly higher in the malignant tumor group than that in benign tumor group. The metabolic pathways of the gut microbiome in the malignant tumor group were significantly different from those in benign tumor group. Furthermore, the study establishes the distinct richness of the gut microbiome in patients with breast cancer with different clinicopathological factors, including ER, PR, Ki-67 level, Her2 status, and tumor grade. These findings suggest that the gut microbiome may be useful for the diagnosis and treatment of malignant breast carcinoma.

Author(s):  
Anna L. Beale ◽  
Joanne A. O’Donnell ◽  
Michael E. Nakai ◽  
Shane Nanayakkara ◽  
Donna Vizi ◽  
...  

Background Risk factors for heart failure with preserved ejection fraction (HFpEF) include hypertension, age, sex, and obesity. Emerging evidence suggests that the gut microbiota independently contributes to each one of these risk factors, potentially mediated via gut microbial‐derived metabolites such as short‐chain fatty acids. In this study, we determined whether the gut microbiota were associated with HFpEF and its risk factors. Methods and Results We recruited 26 patients with HFpEF and 67 control participants from 2 independent communities. Patients with HFpEF were diagnosed by exercise right heart catheterization. We assessed the gut microbiome by bacterial 16S rRNA sequencing and food intake by the food frequency questionnaire. There was a significant difference in α‐diversity (eg, number of microbes) and β‐diversity (eg, type and abundance of microbes) between both cohorts of controls and patients with HFpEF ( P =0.001). We did not find an association between β‐diversity and specific demographic or hemodynamic parameters or risk factors for HFpEF. The Firmicutes to Bacteroidetes ratio, a commonly used marker of gut dysbiosis, was lower, but not significantly so ( P =0.093), in the patients with HFpEF. Compared with controls, the gut microbiome of patients with HFpEF was depleted of bacteria that are short‐chain fatty acid producers. Consistent with this, participants with HFpEF consumed less dietary fiber (17.6±7.7 versus 23.2±8.8 g/day; P =0.016). Conclusions We demonstrate key changes in the gut microbiota in patients with HFpEF, including the depletion of bacteria that generate metabolites known to be important for cardiovascular homeostasis. Further studies are required to validate the role of these gut microbiota and metabolites in the pathophysiology of HFpEF.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 992-993
Author(s):  
Samaneh Farsijani ◽  
Jane Cauley ◽  
Shyamal Peddada ◽  
Lisa Langsetmo ◽  
James Shikany ◽  
...  

Abstract Despite growing evidence supporting the role of protein consumption in promoting muscle health, the possible mediation by gut microbiota remains unclear. Here, we determined the association between the quantity of dietary protein and gut microbiome composition in community-dwelling older adults. We performed a cross-sectional analysis on 775 older men from the Osteoporotic Fractures in Men (MrOS) study with available dietary information and stool samples at visit 4 (2014-16). Protein intake extracted from a brief Food Frequency Questionnaire and adjusted to total energy intake using the residual method. Gut microbial taxa were determined by 16S (v4) sequencing (Greengenes references). 11,534 Operational Taxonomic Units were identified and assigned to 21 phyla with dominance of Firmicutes (45%) and Bacteroidetes (43%). We performed distribution-based analysis (α-diversity), distance-based Permutation Multivariate Analysis of Variance (β-diversity), and taxa abundance (by ANCOM-BC R-package) to determine associations between protein intake and gut microbiome. Mean energy-adjusted protein intake was 62.0±10.8 g/d [0.8±0.3 g/kgBW/d]. Participants with higher protein intake had higher Shannon and Chao1 α-diversity indices (P<0.05). For β-diversity analysis, participants with higher protein intake had a different center in weighted and unweighted UniFrac PCoA vs. those with lower intake (P<0.05) adjusted for age, race, clinical center, energy intake, weight, height, and medications. Tenericutes phylum and several genus-level OTUs, including Klebsiella, Tyzzerella, Christensenellaceae, Ruminococcaceae, Blautia, and Veillonella were differentially abundant between quartiles of protein intake (FDR corrected P<0.05). Our data support an association between dietary protein and gut microbiota diversity, a relationship that could potentially influence physical function and sarcopenia development.


2020 ◽  
Vol 96 (8) ◽  
Author(s):  
Judith Mogouong ◽  
Philippe Constant ◽  
Robert Lavallée ◽  
Claude Guertin

ABSTRACT The gut microbial communities of beetles play crucial roles in their adaptive capacities. Environmental factors such as temperature or nutrition naturally affect the insect microbiome, but a shift in local conditions like the population density on a host tree could also lead to changes in the microbiota. The emerald ash borer (EAB), Agrilus planipennis Fairmaire, is an exotic wood borer that causes environmental and economic damage to ash trees in North America. This study aimed to describe the taxonomic structure of the EAB gut microbiome and explore its potential relationship with borer population size. The number of EAB adults collected per tree through a 75 km transect from an epicenter allowed the creation of distinct classes of population density. The Gammaproteobacteria and Ascomycota predominated in bacterial and fungal communities respectively, as determined by sequencing of the bacterial 16S rRNA gene and the fungal internal transcribed spacer ITS2. Species richness and diversity of the bacterial community showed significant dependence on population density. Moreover, α-diversity and β-diversity analysis revealed some indicator amplicon sequence variants suggesting that the plasticity of the gut microbiome could be related to the EAB population density in host trees.


Author(s):  
Ming-Feng Hou ◽  
Fu Ou-Yang ◽  
Chung-Liang Li ◽  
Fang-Ming Chen ◽  
Chieh-Han Chuang ◽  
...  

AbstractIn Western countries, breast cancer tends to occur in older postmenopausal women. However, in Asian countries, the proportion of younger premenopausal breast cancer patients is increasing. Increasing evidence suggests that the gut microbiota plays a critical role in breast cancer. However, studies on the gut microbiota in the context of breast cancer have mainly focused on postmenopausal breast cancer. Little is known about the gut microbiota in the context of premenopausal breast cancer. This study aimed to comprehensively explore the gut microbial profiles, diagnostic value, and functional pathways in premenopausal breast cancer patients. Here, we analyzed 267 breast cancer patients with different menopausal statuses and age-matched female controls. The α-diversity was significantly reduced in premenopausal breast cancer patients, and the β-diversity differed significantly between breast cancer patients and controls. By performing multiple analyses and classification, 14 microbial markers were identified in the different menopausal statuses of breast cancer. Bacteroides fragilis was specifically found in young women of premenopausal statuses and Klebsiella pneumoniae in older women of postmenopausal statuses. In addition, menopausal-specific microbial markers could exhibit excellent discriminatory ability in distinguishing breast cancer patients from controls. Finally, the functional pathways differed between breast cancer patients and controls. Our findings provide the first evidence that the gut microbiota in premenopausal breast cancer patients differs from that in postmenopausal breast cancer patients and shed light on menopausal-specific microbial markers for diagnosis and investigation, ultimately providing a noninvasive approach for breast cancer detection and a novel strategy for preventing premenopausal breast cancer.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21024-e21024
Author(s):  
Justin Chau ◽  
Meeta Yadav ◽  
Ben Liu ◽  
Muhammad Furqan ◽  
Qun Dai ◽  
...  

e21024 Background: Though the gut microbiome has been associated with immunotherapy (ICI) efficacy in certain cancers, similar correlations between microbiomes at other body sites with treatment response and immune related adverse events (irAEs) in lung cancer (LC) patients receiving ICIs have not been made. We designed a prospective cohort study conducted from 2018-2020 at a single-center academic institution to assess for correlations between the microbiome in various body sites with treatment response and development of irAEs in LC patients treated with ICIs. Methods: Patients with histopathologically confirmed, unresectable/advanced/metastatic LC planned to undergo ICI-based therapy were enrolled between September 2018 and June 2019. Patients must have had measurable disease, ECOG 0-2, and good organ function to be included. Data was collected for analysis from January 2019 to October 2020. Nasal, buccal and gut microbiome samples were obtained prior to ICI initiation, at development of irAEs, improvement of irAEs to grade 1 or less, and at disease progression. 16S rRNA sequenced data was mapped to the SILVA 13.2 database; operational taxonomic unit clusters were analyzed using MicrobiomeAnalyst and METAGENassist. Results: 37 patients were enrolled, and 34 patients were evaluable for this report. 32 healthy controls (HC) from the same geographic region were included to compare baseline gut microbiota. Compared to HC, LC gut microbiota exhibited significantly lower α-diversity. The gut microbiome of patients who did not suffer irAEs were found to have relative enrichment of Bifidobacterium ( p = 0.001) and Desulfovibrio ( p = 0.0002). Responders to combined chemoimmunotherapy exhibited increased Clostridiales ( p = 0.018) but reduced Rikenellaceae ( p = 0.016). In responders to chemoimmunotherapy we also observed enrichment of Finegoldia in nasal microbiome, and increased Megasphaera but reduced Actinobacillus in buccal samples. Longitudinal samples exhibited a trend of α-diversity and certain microbial changes during the development and resolution of irAEs. Conclusions: This pilot study identified significant differences in the gut microbiome between HC and LC patients, and correlates specific bacterial genera to ICI response and irAEs in LC. In addition, it suggests potential predictive utility in nasal and buccal microbiomes, warranting further validation with a larger cohort and mechanistic dissection using preclinical models. Clinical trial information: NCT03688347.


Author(s):  
Ting-Yun Lin ◽  
Szu-Chun Hung

Abstract Background Protein-energy wasting (PEW) is prevalent and associated with adverse outcomes in patients with chronic kidney disease (CKD). However, the pathogenesis of PEW in CKD patients has not been fully identified. The gut microbiota has been implicated in the regulation of host metabolism and energy balance. Therefore, we aimed to explore the association between nutritional status and the composition of the gut microbiota in hemodialysis patients. Methods Gut microbial diversity and taxonomy were examined in 88 hemodialysis patients with PEW (n = 22) and normal nutritional status (n = 66) who were matched 1:3 for age and sex. Nutritional status was assessed by using the 7-point subjective global assessment (SGA) score (1–3 = severe PEW; 4–5 = moderate PEW and 6–7 = normal nutrition). The gut microbiota was assessed by 16S ribosomal RNA gene sequencing. Results Patients with normal nutritional status had a significantly higher body mass index and physical activity and serum albumin levels, but significantly lower levels of inflammatory cytokines than patients with PEW. The most striking finding was that the α-diversity of the gut microbiota was significantly lower in patients with PEW. In a multivariate analysis, the SGA score was independently and positively associated with α-diversity (P = 0.049). Patients with or without PEW were different with respect to the principal coordinate analysis of β-diversity. Notably, the relative abundance of Faecalibacterium prausnitzii, a butyrate-producing bacteria, was markedly reduced in patients with PEW. Conclusion In hemodialysis patients, PEW assessed with the SGA was associated with gut dysbiosis.


Author(s):  
Wenqing Yang ◽  
Liang Tian ◽  
Jiao Luo ◽  
Jialin Yu

Objective The delivery mode is considered to be a significant influencing factor in the early gut microbiota composition, which is associated with the long-term health of the host. In this study, we tried to explore the effects of probiotics on the intestinal microbiota of C-section neonates. Study Design Twenty-six Chinese neonates were enrolled in this study. The neonates were divided into four groups: VD (natural delivery neonates, n = 3), CD (cesarean-born neonates, n = 9), CDL (cesarean-born neonates supplemented with probiotic at a lower dosage, n = 7), and CDH (cesarean-born neonates supplemented with probiotic at a higher dosage, n = 7). Fecal samples were collected on the 3rd, 7th, and 28th day since birth. The V3–V4 region of the 16S ribosomal ribonucleic acid gene was sequenced by next-generation sequencing technology. Results The α-diversity of the intestinal microbiota of cesarean delivery neonates was significantly lower than that of the naturally delivered neonates on the 28th day (p = 0.005). After supplementation with probiotics for 28 days, the α-diversity and the β-diversity of the gut flora in the cesarean-born infants (CDL28 and CDH28) was similar to that in the vaginally delivery infants. Meanwhile, the abundances of Lactobacillus and Bifidobacterium were significantly increased since the 3rd day of probiotic supplementation. Besides, the sustained supplementation of probiotics to neonates would help improve the abundance of the operational taxonomic units in several different Clusters of Orthologous Groups of proteins. Conclusion This study showed that probiotics supplementation to cesarean-born neonates since birth might impact the diversity and function of gut microbiota. Key Points


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Marianne Collard ◽  
Nataleigh Austin ◽  
Ann Tallant ◽  
Patricia Gallagher

Abstract Objectives The goal of this study was to determine if a proprietary muscadine grape seed and skin extract (MGE) inhibits triple negative breast cancer (TNBC) metastasis and alters the gut microbiota. Methods 4T1 TNBC cells were injected into the mammary fat pad of 6-week-old female Balb/c mice. After 2 weeks, tumors were surgically removed and mice were placed into a control group (n = 8) or a treatment group that received 0.1 mg/mL total phenolics MGE (Piedmont R&D) in the drinking water (n = 8). Mice were sacrificed after 4 weeks; tissues and fecal samples were collected for analysis. Immunohistochemistry (Ki67, α-SMA) and hemotoxylin and eosin staining were used to quantify metastases using the inForm© 2.2 software. Gut microbial composition was determined by 16S rRNA sequencing and short chain fatty acids were detected by gas chromatography (Microbiome Insights). Data are expressed as means ± SEM using student's t-test. Results MGE reduced Ki67 cell positivity in the lungs and livers of mice, indicating reduced metastatic proliferation (9.3 ± 0.9% vs 6.2 ± 0.7% and 5.0 ± 1.5% vs 0.77 ± 0.2% cells, respectively; P < 0.01), and decreased cancer associated fibroblasts in the lungs (5.3 ± 1.0% vs 3.0 ± 0.5% cells; P < 0.05), which are associated with metastasis. MGE significantly reduced the number (4.7 ± 0.7 vs 2.2 ± 0.4 tumors/field; P < 0.01) and size (1358 ± 48 vs 1121 ± 47 pixels; P < 0.01) of liver metastases, resulting in decreased metastatic tumor burden (6656 ± 1220 vs 3096 ± 644 total area in pixels; P < 0.01). Attenuated TNBC metastasis correlated with MGE-induced changes in gut microbiota. Alpha diversity (4.15 ± 0.10 vs 4.51 ± 0.13 Shannon index; P < 0.05) and the Firmicutes to Bacteroidetes ratio (0.37 ± 0.07 vs 0.76 ± 0.12; P < 0.05) were significantly increased in MGE-treated mice, indicating enhanced microbial richness and increased energy harvest by the gut microbiome. Butyrate-producing bacteria, such as Ruminococcus, Butyricicoccus and Lachnospiraceae, were increased with MGE (P < 0.05) as well as the anti-inflammatory compound butyrate relative to other short-chain fatty acids (25.0 ± 2.7% vs 75.3 ± 15.5%; P < 0.01). Conclusions These data show that MGE attenuates TNBC metastasis in association with alterations in the gut microbiome, suggesting that MGE may be an effective treatment against TNBC metastatic progression. Funding Sources Chronic Disease Research Fund.


2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Sabrina Ritz ◽  
Daniela Hahn ◽  
Haleluya T. Wami ◽  
Karin Tegelkamp ◽  
Ulrich Dobrindt ◽  
...  

Abstract Background Exocrine pancreatic insufficiency (EPI) is characterized by the loss of active pancreatic enzymes and a resulting severely reduced food digestion. EPI therapy requires orally applied pancreatic enzyme replacement. The gut microbiome is a known mediator of intestinal diseases and may influence the outcome of EPI and the effects of a pancreatic enzyme replacement therapy (PERT). Here, we analyzed the effects of EPI and PERT on the gut microbiome in the model of pancreatic duct ligated minipigs. Results The microbial community composition in pig feces was analyzed by next generation sequencing of 16S rRNA amplicons. The data were evaluated for α- and β-diversity changes and changes at the different Operational Taxonomic Unit (OTU) levels by Shannon–Wiener and inverse Simpson index calculation as well as by Principal Coordinates Analysis based on Bray–Curtis dissimilarity. Microbial α-diversity was reduced after EPI induction and reverted to nearly healthy state after PERT. Analysis of microbial composition and β-diversity showed distinctive clusters of the three study groups and a change towards a composition comparable to healthy animals upon PERT. The relative abundance of possible pathobionts like Escherichia/Shigella, Acinetobacter or Stenotrophomonas was reduced by PERT. Conclusion These data demonstrate that EPI-induced dysbiosis could be reverted by PERT to a nearly healthy state. Elevated α-diversity and the reduction of bacterial overgrowth after PERT promises benefits for EPI patients. Non-invasive microbiome studies may be useful for EPI therapy monitoring and as marker for response to PERT.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1591-1591
Author(s):  
Jirayu Tanprasertsuk ◽  
Justin Shmalberg ◽  
Aashish Jha ◽  
LeeAnn Perry ◽  
Ryan Honaker

Abstract Objectives Dogs share similar gut microbiome (GM) with humans, making them a great model for investigating the effects of probiotics (PR) on GM and health. This randomized control trial examined changes in MB and health outcomes in household dogs after PR supplementation. Methods All dogs recruited were fed human grade cooked food ≥ 1 mo, not fed any cultured food, PR, prebiotics, or on antibiotics ≥ 3 mo, and absent of major diseases. Dogs were randomized to receive a daily dose of PR (20 billion CFU of L. reuteri, P. acidilactici, E. faecium, L. acidophilus, B. animalis, L. fermentum, L. rhamnosus) or placebo (PL) for 4 weeks. Owners completed a health survey and collected stool samples at baseline and 4 weeks after the intervention in both groups. Additional stool samples were collected 2 weeks after stopping the PR in the PR group. GM profiling was performed with metagenomic sequencing. Results Twenty three dogs in the PR and 19 dogs in the PL group completed the trial (5.6 ± 3.0 y, 69% male). PR had no effect on α-diversity. As compared to baseline, changes in β-diversity at the species level in 4.3% of GM were significantly affected by PR at week 4 (P &lt; 0.001) but not at week 6. A significant increase (adj P &lt; 0.01) for ≥ 2-fold in abundance was observed at week 4 as compared to baseline for 41 bacterial taxa, 29 (71%) of which belong in the Lactobacillus genus. The abundance of E. coli also decreased at week 4 in the PR group (2.8 folds, adj P &lt; 0.01). The abundance of these taxa returned to baseline at week 6. Such changes in diversity or abundance were not observed with PL. Dogs fed PR tended to be at a lower risk of diarrhea during the trial (0% vs 16%, P = 0.08). No change in other health outcomes was observed. Conclusions Oral PR supplementation has a small but significant effect on GM in healthy dogs. Findings warrant further investigation with longer duration in populations at a higher risk of gastrointestinal diseases. Funding Sources NomNomNow Inc.


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