scholarly journals Microbiome—Microbial Metabolome—Cancer Cell Interactions in Breast Cancer—Familiar, but Unexplored

Cells ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 293 ◽  
Author(s):  
Edit Mikó ◽  
Tünde Kovács ◽  
Éva Sebő ◽  
Judit Tóth ◽  
Tamás Csonka ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gut Microbiome ◽  
Bacterial Species ◽  
Short Chain Fatty Acids ◽  
Bioactive Metabolites ◽  
Molecular Events ◽  
Acid Metabolites ◽  
Sites Of Action ◽  
Secondary Bile Acids

Breast cancer is a leading cause of death among women worldwide. Dysbiosis, an aberrant composition of the microbiome, characterizes breast cancer. In this review we discuss the changes to the metabolism of breast cancer cells, as well as the composition of the breast and gut microbiome in breast cancer. The role of the breast microbiome in breast cancer is unresolved, nevertheless it seems that the gut microbiome does have a role in the pathology of the disease. The gut microbiome secretes bioactive metabolites (reactivated estrogens, short chain fatty acids, amino acid metabolites, or secondary bile acids) that modulate breast cancer. We highlight the bacterial species or taxonomical units that generate these metabolites, we show their mode of action, and discuss how the metabolites affect mitochondrial metabolism and other molecular events in breast cancer. These metabolites resemble human hormones, as they are produced in a “gland” (in this case, the microbiome) and they are subsequently transferred to distant sites of action through the circulation. These metabolites appear to be important constituents of the tumor microenvironment. Finally, we discuss how bacterial dysbiosis interferes with breast cancer treatment through interfering with chemotherapeutic drug metabolism and availability.

scholarly journals The Microbiome in Autoimmune Liver Diseases: Metagenomic and Metabolomic Changes

2021 ◽  
Vol 12 ◽  
Author(s):  
Yanping Zheng ◽  
Ying Ran ◽  
Hongxia Zhang ◽  
Bangmao Wang ◽  
Lu Zhou
Keyword(s):  
Gut Microbiome ◽  
Metabolic Pathways ◽  
Liver Diseases ◽  
Critical Role ◽  
Short Chain Fatty Acids ◽  
Primary Biliary Cholangitis ◽  
Mechanistic Studies ◽  
Autoimmune Liver Diseases ◽  
Acid Metabolites

Recent studies have identified the critical role of microbiota in the pathophysiology of autoimmune liver diseases (AILDs), including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). Metagenomic studies reveal significant decrease of gut bacterial diversity in AILDs. Although profiles of metagenomic vary widely, Veillonella is commonly enriched in AIH, PBC, and PSC. Apart from gut microbiome, the oral and bile microbiome seem to be associated with these diseases as well. The functional analysis of metagenomics suggests that metabolic pathways changed in the gut microbiome of the patients. Microbial metabolites, including short-chain fatty acids (SCFAs) and microbial bile acid metabolites, have been shown to modulate innate immunity, adaptive immunity, and inflammation. Taken together, the evidence of host–microbiome interactions and in-depth mechanistic studies needs further accumulation, which will offer more possibilities to clarify the mechanisms of AILDs and provide potential molecular targets for the prevention and treatment in the future.

scholarly journals Dietary Patterns Affect the Gut Microbiome—The Link to Risk of Cardiometabolic Diseases

2018 ◽  
Vol 148 (9) ◽  
pp. 1402-1407 ◽  
Author(s):  
Alyssa M Tindall ◽  
Kristina S Petersen ◽  
Penny M Kris-Etherton
Keyword(s):  
Dietary Patterns ◽  
Gut Microbiome ◽  
Disease Risk ◽  
Bacterial Species ◽  
Short Chain Fatty Acids ◽  
Cardiometabolic Disease ◽  
Metabolic Products ◽  
Vegetarian Diets ◽  
Secondary Bile Acids ◽  
Cardiometabolic Disease Risk

Abstract Clusters of bacterial species within the gut microenvironment, or gut enterotype, have been correlated with cardiometabolic disease risk. The metabolic products and metabolites that bacteria produce, such as short-chain fatty acids, secondary bile acids, and trimethylamine, may also affect the microbial community and disease risk. Diet has a direct impact on the gut microenvironment by providing substrates to and promoting the colonization of resident bacteria. To date, few dietary patterns have been evaluated for their effect on the gut microbiome, but the Mediterranean diet and Vegetarian diets have shown favorable effects for both the gut microbiome and cardiometabolic disease risk. This review examines the gut microbiome as a mediator between these dietary patterns and cardiometabolic disease risk.

scholarly journals Gut Microbiome: Profound Implications for Diet and Disease

Nutrients ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1613 ◽  
Author(s):  
Ronald Hills ◽  
Benjamin Pontefract ◽  
Hillary Mishcon ◽  
Cody Black ◽  
Steven Sutton ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Bacterial Species ◽  
Intestinal Bacteria ◽  
Short Chain Fatty Acids ◽  
E Coli ◽  
Beneficial Effects ◽  
Microbial Profile ◽  
Irritable Bowel ◽  
Prebiotic Fiber

The gut microbiome plays an important role in human health and influences the development of chronic diseases ranging from metabolic disease to gastrointestinal disorders and colorectal cancer. Of increasing prevalence in Western societies, these conditions carry a high burden of care. Dietary patterns and environmental factors have a profound effect on shaping gut microbiota in real time. Diverse populations of intestinal bacteria mediate their beneficial effects through the fermentation of dietary fiber to produce short-chain fatty acids, endogenous signals with important roles in lipid homeostasis and reducing inflammation. Recent progress shows that an individual’s starting microbial profile is a key determinant in predicting their response to intervention with live probiotics. The gut microbiota is complex and challenging to characterize. Enterotypes have been proposed using metrics such as alpha species diversity, the ratio of Firmicutes to Bacteroidetes phyla, and the relative abundance of beneficial genera (e.g., Bifidobacterium, Akkermansia) versus facultative anaerobes (E. coli), pro-inflammatory Ruminococcus, or nonbacterial microbes. Microbiota composition and relative populations of bacterial species are linked to physiologic health along different axes. We review the role of diet quality, carbohydrate intake, fermentable FODMAPs, and prebiotic fiber in maintaining healthy gut flora. The implications are discussed for various conditions including obesity, diabetes, irritable bowel syndrome, inflammatory bowel disease, depression, and cardiovascular disease.

scholarly journals Muscadine Grape Extract Reduces Lung and Liver Metastasis in Mice with Triple Negative Breast Cancer in Association with Changes in the Gut Microbiome (P05-017-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Marianne Collard ◽  
Nataleigh Austin ◽  
Ann Tallant ◽  
Patricia Gallagher
Keyword(s):  
Breast Cancer ◽  
Fatty Acids ◽  
Gut Microbiota ◽  
Triple Negative Breast Cancer ◽  
Gut Microbiome ◽  
Triple Negative ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Muscadine Grape ◽  
Chain Fatty Acids

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.

scholarly journals Association of Flavonifractor plautii, a Flavonoid-Degrading Bacterium, with the Gut Microbiome of Colorectal Cancer Patients in India

mSystems ◽  
2019 ◽  
Vol 4 (6) ◽  
Author(s):  
Ankit Gupta ◽  
Darshan B. Dhakan ◽  
Abhijit Maji ◽  
Rituja Saxena ◽  
Vishnu Prasoodanan P.K. ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Gut Microbiome ◽  
Association Studies ◽  
Bacterial Species ◽  
Developed Countries ◽  
Learning Approaches ◽  
Gene Markers ◽  
Degrading Bacterium

ABSTRACT Recently, dysbiosis in the human gut microbiome and shifts in the relative abundances of several bacterial species have been recognized as important factors in colorectal cancer (CRC). However, these studies have been carried out mainly in developed countries where CRC has a high incidence, and it is unclear whether the host-microbiome relationships deduced from these studies can be generalized to the global population. To test if the documented associations between the microbiome and CRC are conserved in a distinct context, we performed metagenomic and metabolomic association studies on fecal samples from 30 CRC patients and 30 healthy controls from two different locations in India, followed by a comparison of CRC data available from other populations. We confirmed the association of Bacteroides and other bacterial taxa with CRC that have been previously reported in other studies. However, the association of CRC with Flavonifractor plautii in Indian patients emerged as a novel finding. The plausible role of F. plautii appears to be linked with the degradation of beneficial anticarcinogenic flavonoids, which was also found to be significantly correlated with the enzymes and modules involved in flavonoid degradation within Indian CRC samples. Thus, we hypothesize that the degradation of beneficial flavonoids might be playing a role in cancer progression within this Indian cohort. We also identified 20 potential microbial taxonomic markers and 33 potential microbial gene markers that discriminate the Indian CRC from healthy microbiomes with high accuracy based on machine learning approaches. IMPORTANCE This study provides novel insights on the CRC-associated microbiome of a unique cohort in India, reveals the potential role of a new bacterium in CRC, and identifies cohort-specific biomarkers, which can potentially be used in noninvasive diagnosis of CRC. The study gains additional significance, as India is among the countries with a very low incidence of CRC, and the diet and lifestyle in India have been associated with a distinct gut microbiome in healthy Indians compared to other global populations. Thus, in this study, we hypothesize a unique relationship between CRC and the gut microbiome in an Indian population.

scholarly journals Interdisciplinary insights into the link between gut microbiome and gastric carcinogenesis—what is currently known?

2021 ◽  
Author(s):  
Karolina Kaźmierczak-Siedlecka ◽  
Agnieszka Daca ◽  
Giandomenico Roviello ◽  
Martina Catalano ◽  
Karol Połom
Keyword(s):  
Gastric Cancer ◽  
Gut Microbiome ◽  
Short Chain Fatty Acids ◽  
Gastric Carcinogenesis ◽  
Point Of View ◽  
Molecular Techniques ◽  
Nitroso Compounds ◽  
Gastric Microbiota ◽  
Development Of Gastric Cancer

AbstractCurrently, gastric cancer is one of the leading death-related cancer globally. The etiopathogenesis of gastric cancer is multifactorial and includes among others dysbiotic alterations of gastric microbiota. Molecular techniques revealed that stomach is not a sterile organ and it is resides with ecosystem of microbes. Due to the fact that the role of Helicobacter pylori infection in development of gastric cancer is established and well-studied, this paper is mainly focused on the role of other bacterial as well as viral and fungal gut microbiota imbalance in gastric carcinogenesis. Notably, not only the composition of gastric microbiota may play an important role in development of gastric cancer, but also its activity. Microbial metabolites, such as short-chain fatty acids, polyamines, N-nitroso compounds, and lactate, may significantly affect gastric carcinogenesis. Therefore, this paper discussed aforementioned aspects with the interdisciplinary insights (regarding also immunological point of view) into the association between gut microbiome and gastric carcinogenesis based on up-to-date studies.

scholarly journals Metagenome-wide association study of gut microbiome features for myositis

2021 ◽  
Author(s):  
Yimin Li ◽  
Jun Xu ◽  
Zijun Li ◽  
Yixue Guo ◽  
Xiaoyan Xing ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Gut Microbiome ◽  
Association Studies ◽  
Bacterial Species ◽  
Biological Pathways ◽  
Healthy Controls ◽  
E Coli

Objective: The clinical relevance and pathogenic role of gut microbiome in both myositis and its associated interstitial lung disease (ILD) are still unclear. The purpose of this study was to investigate the role of gut microbiome in myositis through comprehensive metagenomic-wide association studies (MWAS). Methods We conducted MWAS of the myositis gut microbiome in a Chinese cohort by using whole-genome shotgun sequencing of high depth, including 30 myositis patients and 31 healthy controls (HC). Among the myositis patients, 11 developed rapidly progressive interstitial lung disease (RP-ILD) and 10 had chronic ILD (C-ILD). Our MWAS consisted of both overall distribution level of the bacteria analysis and pathway analysis. Receiver operating characteristic curve (ROC) analysis was performed to identify novel gut bacterial species associated with myositis or myositis-associated RP-ILD, and to evaluate their diagnostic values. Results Apparent discrepancy in β diversities of metagenome was found in the comparison of myositis and HC, RP-ILD and C-ILD in myositis. Analysis for overall distribution level of the bacteria showed Alistipes onderdonkii, Parabacteroides distasonis and Escherichia coli were upregulated, Lachnospiraceae bacterium GAM79, Roseburia intestinalis, and Akkermansia muciniphila were downregulated in patients with myositis compared to HC. Bacteroides thetaiotaomicron, Parabacteroides distasonis and Escherichia coli were upregulated, Bacteroides A1C1 and Bacteroides xylanisolvens were downregulated in RP-ILD cases compared with C-ILD cases. A variety of biological pathways related to metabolism were enriched in the myositis and HC, RP-ILD and C-ILD comparison. And in the analyses for microbial contribution in metagenomic biological pathways, we have found that E. coli played an important role in the pathway expression in both myositis group and myositis-associated RP-ILD group. Anti-PL-12 antibody, anti-Ro-52 antibody, and anti-EJ antibody were found to have positive correlation with bacterial diversity (Shannon-wiener diversity index and Chao1, richness estimator) between myositis group and control groups. The combination of E. coli and R. intestinalis could distinguish myositis group from Healthy controls effectively. R. intestinalis can also be applied in the distinguishment of RP-ILD group vs. C-ILD group in myositis paitents. Conclusion Our MWAS study first revealed the link between gut microbiome and pathgenesis of myositis, which may help us understand the role of gut microbiome in the etiology of myositis and myositis-associated RP-ILD.

scholarly journals The Metabolomic Signatures of Weight Change

Metabolites ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 67 ◽  
Author(s):  
Amrita Vijay ◽  
Ana M Valdes
Keyword(s):  
Weight Change ◽  
Gut Microbiome ◽  
Short Chain Fatty Acids ◽  
Health Concern ◽  
Middle Income ◽  
Major Health ◽  
Middle Income Countries ◽  
Current Review ◽  
Considerable Body

Obesity represents a major health concern, not just in the West but increasingly in low and middle income countries. In order to develop successful strategies for losing weight, it is essential to understand the molecular pathogenesis of weight change. A number of pathways, implicating oxidative stress but also the fundamental regulatory of insulin, have been implicated in weight gain and in the regulation of energy expenditure. In addition, a considerable body of work has highlighted the role of metabolites generated by the gut microbiome, in particular short chain fatty acids, in both processes. The current review provides a brief understanding of the mechanisms underlying the associations of weight change with changes in lipid and amino acid metabolism, energy metabolism, dietary composition and insulin dynamics, as well as the influence of the gut microbiome. The changes in metabolomic profiles and the models outlined can be used as an accurate predictor for obesity and obesity related disorders.

scholarly journals The role of the gut microbiome in graft fibrosis after pediatric liver transplantation

2020 ◽  
Author(s):  
Tian Qin ◽  
Jingyuan Fu ◽  
Henkjan J. Verkade
Keyword(s):  
Liver Transplantation ◽  
Gut Microbiome ◽  
Current Knowledge ◽  
Solid Organ Transplantation ◽  
Short Chain Fatty Acids ◽  
Solid Organ ◽  
Microbial Composition ◽  
Term Survival ◽  
End Stage

Abstract Liver transplantation (LT) is a life-saving option for children with end-stage liver disease. However, about 50% of patients develop graft fibrosis in 1 year after LT, with normal liver function. Graft fibrosis may progress to cirrhosis, resulting in graft dysfunction and ultimately the need for re-transplantation. Previous studies have identified various risk factors for the post-LT fibrogenesis, however, to date, neither of the factors seems to fully explain the cause of graft fibrosis. Recently, evidence has accumulated on the important role of the gut microbiome in outcomes after solid organ transplantation. As an altered microbiome is present in pediatric patients with end-stage liver diseases, we hypothesize that the persisting alterations in microbial composition or function contribute to the development of graft fibrosis, for example by bacteria translocation due to increased intestinal permeability, imbalanced bile acids metabolism, and/or decreased production of short-chain fatty acids (SCFAs). Subsequently, an immune response can be activated in the graft, together with the stimulation of fibrogenesis. Here we review current knowledge about the potential mechanisms by which alterations in microbial composition or function may lead to graft fibrosis in pediatric LT and we provide prospective views on the efficacy of gut microbiome manipulation as a therapeutic target to alleviate the graft fibrosis and to improve long-term survival after LT.

Sign in / Sign up

Export Citation Format

Share Document