scholarly journals The Role of the Gut Microbiome in Colorectal Cancer Development and Therapy Response

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1406 ◽  
Author(s):  
Lidia Sánchez-Alcoholado ◽  
Bruno Ramos-Molina ◽  
Ana Otero ◽  
Aurora Laborda-Illanes ◽  
Rafael Ordóñez ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Fatty Acids ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Cancer Metabolism ◽  
Bacterial Species ◽  
Therapy Response ◽  
Short Chain Fatty Acids ◽  
Bacterial Populations ◽  
High Fiber

Colorectal cancer (CRC) is the third most common cancer worldwide and the leading cause of cancer-related deaths. Recently, several studies have demonstrated that gut microbiota can alter CRC susceptibility and progression by modulating mechanisms such as inflammation and DNA damage, and by producing metabolites involved in tumor progression or suppression. Dysbiosis of gut microbiota has been observed in patients with CRC, with a decrease in commensal bacterial species (butyrate-producing bacteria) and an enrichment of detrimental bacterial populations (pro-inflammatory opportunistic pathogens). CRC is characterized by altered production of bacterial metabolites directly involved in cancer metabolism including short-chain fatty acids and polyamines. Emerging evidence suggests that diet has an important impact on the risk of CRC development. The intake of high-fiber diets and the supplementation of diet with polyunsaturated fatty acids, polyphenols and probiotics, which are known to regulate gut microbiota, could be not only a potential mechanism for the reduction of CRC risk in a primary prevention setting, but may also be important to enhance the response to cancer therapy when used as adjuvant to conventional treatment for CRC. Therefore, a personalized modulation of the pattern of gut microbiome by diet may be a promising approach to prevent the development and progression of CRC and to improve the efficacy of antitumoral therapy.

scholarly journals Meta-analysis of the Parkinson’s disease gut microbiome suggests alterations linked to intestinal inflammation

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Stefano Romano ◽  
George M. Savva ◽  
Janis R. Bedarf ◽  
Ian G. Charles ◽  
Falk Hildebrand ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Fatty Acids ◽  
Parkinson's Disease ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Intestinal Inflammation ◽  
Meta Analysis ◽  
Gastrointestinal Symptoms ◽  
Short Chain Fatty Acids ◽  
Inflammatory Status

AbstractThe gut microbiota is emerging as an important modulator of neurodegenerative diseases, and accumulating evidence has linked gut microbes to Parkinson’s disease (PD) symptomatology and pathophysiology. PD is often preceded by gastrointestinal symptoms and alterations of the enteric nervous system accompany the disease. Several studies have analyzed the gut microbiome in PD, but a consensus on the features of the PD-specific microbiota is missing. Here, we conduct a meta-analysis re-analyzing the ten currently available 16S microbiome datasets to investigate whether common alterations in the gut microbiota of PD patients exist across cohorts. We found significant alterations in the PD-associated microbiome, which are robust to study-specific technical heterogeneities, although differences in microbiome structure between PD and controls are small. Enrichment of the genera Lactobacillus, Akkermansia, and Bifidobacterium and depletion of bacteria belonging to the Lachnospiraceae family and the Faecalibacterium genus, both important short-chain fatty acids producers, emerged as the most consistent PD gut microbiome alterations. This dysbiosis might result in a pro-inflammatory status which could be linked to the recurrent gastrointestinal symptoms affecting PD patients.

scholarly journals Microbiota-Associated Metabolites and Related Immunoregulation in Colorectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4054
Author(s):  
Yan Chen ◽  
Ying-Xuan Chen
Keyword(s):  
Colorectal Cancer ◽  
Fatty Acids ◽  
Gut Microbiota ◽  
Immune Responses ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Indole Derivatives ◽  
Human Gut ◽  
Growing Body ◽  
Specific Influence

A growing body of research has found close links between the human gut microbiota and colorectal cancer (CRC), associated with the direct actions of specific bacteria and the activities of microbiota-derived metabolites, which are implicated in complex immune responses, thus influencing carcinogenesis. Diet has a significant impact on the structure of the microbiota and also undergoes microbial metabolism. Some metabolites, such as short-chain fatty acids (SCFAs) and indole derivatives, act as protectors against cancer by regulating immune responses, while others may promote cancer. However, the specific influence of these metabolites on the host is conditional. We reviewed the recent insights on the relationships among diet, microbiota-derived metabolites, and CRC, focusing on their intricate immunomodulatory responses, which might influence the progression of colorectal cancer.

Abstract P485: Association of Hypertension With the Gut Microbiome and Serum Short-chain Fatty Acids

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Moira K Differding ◽  
Lawrence J Appel ◽  
Nisa Maruthur ◽  
Stephen Juraschek ◽  
Edgar R Miller ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Short Chain Fatty Acids ◽  
Self Report ◽  
Short Chain ◽  
Inverse Association ◽  
Negatively Associated ◽  
Adult Cancer Survivors ◽  
Chain Fatty Acids

Background: Murine models indicate that gut microbiota, and the short chain fatty acids (SCFAs) they produce from fermentation of fiber, play a role in blood pressure (BP) regulation. However, few human studies have examined how gut microbiota and serum SCFAs are associated with hypertension. Objective: We examined associations of gut microbiota composition and serum SCFAs with hypertension and BP, hypothesizing an inverse association with serum SCFAs. Methods: We performed a cross-sectional analysis of baseline data from a trial of overweight and obese adult cancer survivors. We measured 1 ) the gut microbiome by extracting microbial DNA from stool and sequencing the 16S rRNA V4 region and 2 ) serum SCFA using liquid chromatography mass spectrometry. Hypertension was defined as systolic BP ≥ 130, diastolic BP ≥ 80 mmHg, self-report, or use of hypertension medications. We used beta-binomial models to test differential abundance of microbial amplicon sequence variants by hypertension , and linear regression to examine log-transformed SCFAs with BP. We adjusted models for age, sex, race, fiber, BMI and medications (in BP models). Results: Of 111 participants with complete data, 73 had hypertension. Hypertensive participants differed by age (mean 62 vs. 56y) and sex (73% vs. 90% female), but not race (46% black) or BMI (mean 35 kg/m 2 ). Alpha and beta diversity were not associated with hypertension (Ps>0.05). Hypertensive participants had higher abundance of Bacteroides, Parabacteroides, Bifidobacterium and Escherichia , and lower Lachnospiraceae, Haemophilus and Faecalibacterium ( Figure) . Serum acetate was negatively associated with systolic BP (β=-3.3 mmHg difference per 1 SD increment acetate, 95% CI: -6.1, -0.6); other SCFAs were not associated (Ps>0.05). Conclusion: A Bacteroides dominated microbiota was positively associated with hypertension. Acetate, the most abundant circulating SCFA, was negatively associated with BP. Determining whether the associations are causal or not warrants further investigation.

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 The Role of the Gut Microbiome in Colorectal Cancer

2018 ◽  
Vol 31 (03) ◽  
pp. 192-198 ◽  
Author(s):  
Grace Chen
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Microbial Community ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Intestinal Health ◽  
Genotoxic Effects ◽  
Bacterial Populations ◽  
Health And Disease

AbstractThere is increasing evidence that the gut microbiome, which consists of trillions of microbes representing over 1,000 species of bacteria with over 3 million genes, significantly impacts intestinal health and disease. The gut microbiota not only is capable of promoting intestinal homeostasis and antitumor responses but can also contribute to chronic dysregulated inflammation as well as have genotoxic effects that lead to carcinogenesis. Whether the gut microbiota maintains health or promotes colon cancer may ultimately depend on the composition of the gut microbiome and the balance within the microbial community of protective and detrimental bacterial populations. Disturbances in the normal balanced state of a healthful microbiome, known as dysbiosis, have been observed in patients with colorectal cancer (CRC); however, whether these alterations precede and cause CRC remains to be determined. Nonetheless, studies in mice strongly suggest that the gut microbiota can modulate susceptibility to CRC, and therefore may serve as both biomarkers and therapeutic targets.

scholarly journals Microbiota-directed fibre activates both targeted and secondary metabolic shifts in the distal gut

2019 ◽  
Author(s):  
Leszek Michalak ◽  
John Christian Gaby ◽  
Leidy Lagos ◽  
Sabina Leanti La Rosa ◽  
Torgeir R. Hvidsten ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Gut Microbiome ◽  
Short Chain Fatty Acids ◽  
Structural Features ◽  
High Impact ◽  
Bacterial Populations ◽  
Target Populations ◽  
Societal Needs ◽  
Specific Polysaccharide ◽  
Polysaccharide Utilization Loci

ABSTRACTBeneficial modulation of the gut microbiome has high-impact implications not only in humans, but also in livestock that sustain our current societal needs. In this context, we have tailored an acetylated galactoglucomannan (AcGGM) fibre to match unique enzymatic capabilities of Roseburia and Faecalibacterium species, both renowned butyrate-producing gut commensals. The accuracy of AcGGM was tested within the complex endogenous gut microbiome of pigs, wherein we resolved 355 metagenome-assembled genomes together with quantitative metaproteomes. In AcGGM-fed pigs, both target populations differentially expressed AcGGM-specific polysaccharide utilization loci, including novel, mannan-specific esterases that are critical to its deconstruction. However, AcGGM-inclusion also manifested a “butterfly effect”, whereby numerous metabolic changes and interdependent cross-feeding pathways were detected in neighboring non-mannolytic populations that produce short-chain fatty acids. Our findings show that intricate structural features and acetylation patterns of dietary fibre can be customized to specific bacterial populations, with potential to create greater modulatory effects at large.

scholarly journals Antibiotic Exposure Has Sex-Dependent Effects on the Gut Microbiota and Metabolism of Short-Chain Fatty Acids and Amino Acids in Mice

mSystems ◽  
2019 ◽  
Vol 4 (4) ◽  
Author(s):  
Hongchang Gao ◽  
Qi Shu ◽  
Jiuxia Chen ◽  
Kai Fan ◽  
Pengtao Xu ◽  
...  
Keyword(s):  
Amino Acids ◽  
Fatty Acids ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Short Chain Fatty Acids ◽  
Antibiotic Exposure ◽  
Male Mice ◽  
Female Mice ◽  
Structural Composition ◽  
Host Metabolism

ABSTRACT The gut microbiota has the capability to regulate homeostasis of the host metabolism. Since antibiotic exposure can adversely affect the microbiome, we hypothesized that antibiotic effects on the gut microbiota and host metabolism are sex dependent. In this study, we examined the effects of antibiotic treatments, including vancomycin (Vanc) and ciprofloxacin-metronidazole (CiMe), on the gut microbiome and metabolome in colonic contents and tissues in both male and female mice. We found that the relative abundances and structural composition of Firmicutes were significantly reduced in female mice after both Vanc and CiMe treatments but in male mice only after treatment with Vanc. However, Vanc exposure considerably altered the relative abundances and structural composition of representatives of the Proteobacteria especially in male mice. The levels of short-chain fatty acids (SCFAs; acetate, butyrate, and propionate) in colonic contents and tissues were significantly decreased in female mice after both antibiotic treatments, while these reductions were detected in male mice only after Vanc treatment. However, another SCFA, formate, exhibited the opposite tendency in colonic tissues. Both antibiotic exposures significantly decreased the levels of alanine, branched-chain amino acids (BCAAs; leucine, isoleucine, and valine) and aromatic amino acids (AAAs; phenylalanine and tyrosine) in colonic contents of female mice but not in male mice. Additionally, female mice had much greater correlations between microbe and metabolite than male mice. These findings suggest that sex-dependent effects should be considered for antibiotic-induced modifications of the gut microbiota and host metabolism. IMPORTANCE Accumulating evidence shows that the gut microbiota regulates host metabolism by producing a series of metabolites, such as amino acids, bile acids, fatty acids, and others. These metabolites have a positive or negative effect on host health. Antibiotic exposure can disrupt the gut microbiota and thereby affect host metabolism and physiology. However, there are a limited number of studies addressing whether antibiotic effects on the gut microbiota and host metabolism are sex dependent. In this study, we uncovered a sex-dependent difference in antibiotic effects on the gut microbiota and metabolome in colonic contents and tissues in mice. These findings reveal that sex-dependent effects need to be considered for antibiotic use in scientific research or clinical practice. Moreover, this study will also give an important direction for future use of antibiotics to modify the gut microbiome and host metabolism in a sex-specific manner.

Sign in / Sign up

Export Citation Format

Share Document