scholarly journals Novel Insights Into the Interactions Between the Gut Microbiome, Inflammasomes, and Gasdermins During Colorectal Cancer

2022 ◽  
Vol 11 ◽  
Author(s):  
Giuseppe Privitera ◽  
Nitish Rana ◽  
Franco Scaldaferri ◽  
Alessandro Armuzzi ◽  
Theresa T. Pizarro
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiome ◽  
Active Role ◽  
Current Evidence ◽  
Microbiome Composition ◽  
Downstream Effectors ◽  
Intestinal Dysbiosis ◽  
Causative Relationship ◽  
Colonic Carcinogenesis ◽  
And Function

Colorectal cancer (CRC) is one of the most prevalent and deadly forms of cancer in Western countries. Inflammation is a well-known driver of colonic carcinogenesis; however, its role in CRC extends beyond colitis-associated cancer. Over the last decades, numerous associations between intestinal dysbiosis and CRC have been identified, with more recent studies providing mechanistic evidence of a causative relationship. Nonetheless, much remains to be discovered regarding the precise implications of microbiome alterations in the pathogenesis of CRC. Research confirms the importance of a bidirectional crosstalk between the gut microbiome and the mucosal immune system in which inflammasomes, multiprotein complexes that can sense “danger signals,” serve as conduits by detecting microbial signals and activating innate immune responses, including the induction of microbicidal activities that can alter microbiome composition. Current evidence strongly supports an active role for this “inflammasome–microbiome axis” in the initiation and development of CRC. Furthermore, the gasdermin (GSDM) family of proteins, which are downstream effectors of the inflammasome that are primarily known for their role in pyroptosis, have been recently linked to CRC pathogenesis. These findings, however, do not come without controversy, as pyroptosis is reported to exert both anti- and protumorigenic functions. Furthermore, the multi-faceted interactions between GSDMs and the gut microbiome, as well as their importance in CRC, have only been superficially investigated. In this review, we summarize the existing literature supporting the importance of the inflammasome–microbiota axis, as well as the activation and function of GSDMs, to gain a better mechanistic understanding of CRC pathogenesis.

scholarly journals Interaction between Host MicroRNAs and the Gut Microbiota in Colorectal Cancer

mSystems ◽  
2018 ◽  
Vol 3 (3) ◽  
Author(s):  
Ce Yuan ◽  
Michael B. Burns ◽  
Subbaya Subramanian ◽  
Ran Blekhman
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Gut Microbiota ◽  
Mirna Expression ◽  
Gut Microbiome ◽  
Noncoding Rna ◽  
Microbial Community Composition ◽  
Host Cells ◽  
Microbiome Composition ◽  
Small Noncoding Rna

ABSTRACT Although variation in gut microbiome composition has been linked with colorectal cancer (CRC), the factors that mediate the interactions between CRC tumors and the microbiome are poorly understood. MicroRNAs (miRNAs) are known to regulate CRC progression and are associated with patient survival outcomes. In addition, recent studies suggested that host miRNAs can also regulate bacterial growth and influence the composition of the gut microbiome. Here, we investigated the association between miRNA expression and microbiome composition in human CRC tumor and normal tissues. We identified 76 miRNAs as differentially expressed (DE) in tissue from CRC tumors and normal tissue, including the known oncogenic miRNAs miR-182, miR-503, and mir-17~92 cluster. These DE miRNAs were correlated with the relative abundances of several bacterial taxa, including Firmicutes , Bacteroidetes , and Proteobacteria . Bacteria correlated with DE miRNAs were enriched with distinct predicted metabolic categories. Additionally, we found that miRNAs that correlated with CRC-associated bacteria are predicted to regulate targets that are relevant for host-microbiome interactions and highlight a possible role for miRNA-driven glycan production in the recruitment of pathogenic microbial taxa. Our work characterized a global relationship between microbial community composition and miRNA expression in human CRC tissues. IMPORTANCE Recent studies have found an association between colorectal cancer (CRC) and the gut microbiota. One potential mechanism by which the microbiota can influence host physiology is through affecting gene expression in host cells. MicroRNAs (miRNAs) are small noncoding RNA molecules that can regulate gene expression and have important roles in cancer development. Here, we investigated the link between the gut microbiota and the expression of miRNA in CRC. We found that dozens of miRNAs are differentially regulated in CRC tumors and adjacent normal colon and that these miRNAs are correlated with the abundance of microbes in the tumor microenvironment. Moreover, we found that microbes that have been previously associated with CRC are correlated with miRNAs that regulate genes related to interactions with microbes. Notably, these miRNAs likely regulate glycan production, which is important for the recruitment of pathogenic microbial taxa to the tumor. This work provides a first systems-level map of the association between microbes and host miRNAs in the context of CRC and provides targets for further experimental validation and potential interventions.

scholarly journals Dysbiosis of Gut Microbiota with Increased Trimethylamine N-oxide Level in Patients with Large Artery Atherosclerotic and Cardioembolic Strokes

2020 ◽  
Author(s):  
Dong-Juan Xu ◽  
Kai Cheng Wang ◽  
Lin-Bo Yuan ◽  
Qiong-Qiong Lin ◽  
Hong-Fei Li ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Control Group ◽  
Large Artery ◽  
Microbiome Composition ◽  
Plaque Area ◽  
Liquid Chromatography Tandem Mass ◽  
And Function ◽  
Dietary Choline ◽  
Asymptomatic Control

Abstract Background — With the establishment of the concept of the gut–brain axis, increasing evidence has shown that the gut microbiome plays an important role in the pathogenesis of cardiovascular diseases. Gut bacteria can transform dietary choline, L-carnitine, and trimethylamine N -oxide (TMAO) into trimethylamine, which can be oxidized into TMAO again in the liver and participate in atherogenesis. However, only few studies have described alterations in the gut microbiota composition and function in cardioembolic (CE) and large artery atherosclerotic (LAA) strokes. Methods and Results — A case–control study was performed on patients with LAA and CE strokes. TMAO was determined via liquid chromatography tandem mass spectrometry. Gut microbiome was profiled through Illumina sequencing of the 16S ribosomal RNA gene (V4–V5 regions). The TMAO levels in the plasma of patients with LAA and CE strokes were significantly increased (TMAO: LAA stroke, 2931±456.4 ng/mL vs. CE stroke, 4220±577.6 ng/mL vs. control, 1663±117.8 ng/mL; P < 0.05). The TMAO level in patients with LAA stroke was positively correlated with the carotid plaque area (rho = 0.333, 95% confidence interval = 0.08 to 0.55, and P = 0.0093). The composition and function of gut microbiomes in the LAA and CE stroke groups were significantly different from those of the asymptomatic control. In addition to the significantly increased α and β diversities, the gut microbiome composition and function showed that the LAA group had more microorganisms than the asymptomatic control group; such microorganisms convert dietary source choline, TMAO to TMA. Parabacteroides and Streptococcus exhibited the strongest association with LAA and CE strokes. Conclusions — This study established the compositional and functional alterations of gut microbiomes in patients with LAA and CE strokes and the relationship between plasma TMAO and gut microbiota. The findings suggest the potential of using gut microbiota as a biomarker for patients with LAA and CE strokes.

scholarly journals Distinct Colon Mucosa Microbiomes associated with Tubular Adenomas and Serrated Polyps

2021 ◽  
Author(s):  
Julio Avelar-Barragan ◽  
Lauren DeDecker ◽  
Zachary Lu ◽  
Bretton Coppedge ◽  
William Karnes ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiome ◽  
Microbial Community Composition ◽  
Tubular Adenoma ◽  
Colon Mucosa ◽  
Fecal Samples ◽  
Serrated Polyps ◽  
Microbiome Composition ◽  
Serrated Polyp ◽  
Mechanisms Of Carcinogenesis

Background: Colorectal cancer is the second most deadly and third most common cancer in the world. Its development is heterogenous, with multiple mechanisms of carcinogenesis. Two distinct mechanisms include the adenoma-carcinoma sequence and the serrated pathway. The gut microbiome has been identified as a key player in the adenoma-carcinoma sequence, but its role in serrated carcinogenesis is unclear. In this study, we characterized the gut microbiome of 140 polyp-free and polyp-bearing individuals using colon mucosa and fecal samples to determine if microbiome composition was associated with each of the two key pathways. Results: We discovered significant differences between colon mucosa and fecal samples, explaining 14% of the variation observed in the microbiome. Multiple mucosal samples were collected from each individual to investigate the gut microbiome for differences between polyp and healthy intestinal tissue, but no such differences were found. Colon mucosa sampling revealed that the microbiomes of individuals with tubular adenomas and serrated polyps were significantly different from each other and polyp-free individuals, explaining 2-10% of the variance in the microbiome. Further analysis revealed differential abundances of Eggerthella lenta, Clostridium scindens, and three microbial genes across tubular adenoma, serrated polyp, and polyp-free cases. Conclusion: By directly sampling the colon mucosa and distinguishing between the different developmental pathways of colorectal cancer, this study helps characterize potential mechanistic targets and diagnostic biomarkers for serrated carcinogenesis. This research also provides insight into multiple microbiome sampling strategies by assessing each methods practicality and effect on microbial community composition.

scholarly journals Metformin Affects Gut Microbiome Composition and Function and Circulating Short-Chain Fatty Acids: A Randomized Trial

Diabetes Care ◽  
2021 ◽  
pp. dc202257
Author(s):  
Noel T. Mueller ◽  
Moira K. Differding ◽  
Mingyu Zhang ◽  
Nisa M. Maruthur ◽  
Stephen P. Juraschek ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Randomized Trial ◽  
Gut Microbiome ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Microbiome Composition ◽  
And Function ◽  
Chain Fatty Acids

scholarly journals Seasonal variation in nutrient utilization shapes gut microbiome structure and function in wild giant pandas

2017 ◽  
Vol 284 (1862) ◽  
pp. 20170955 ◽  
Author(s):  
Qi Wu ◽  
Xiao Wang ◽  
Yun Ding ◽  
Yibo Hu ◽  
Yonggang Nie ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Cell Cycle Control ◽  
Nutrient Utilization ◽  
Giant Pandas ◽  
Microbiome Composition ◽  
Leaf Stage ◽  
Bamboo Shoots ◽  
And Function ◽  
Gut Microbial Community ◽  
Metagenomic Approach

Wild giant pandas use different parts of bamboo (shoots, leaves and stems) and different bamboo species at different times of the year. Their usage of bamboo can be classified temporally into a distinct leaf stage, shoot stage and transition stage. An association between this usage pattern and variation in the giant panda gut microbiome remains unknown. Here, we found associations using a gut metagenomic approach and nutritional analyses whereby diversity of the gut microbial community in the leaf and shoot stages was significantly different. Functional metagenomic analysis showed that in the leaf stage, bacteria species over-represented genes involved in raw fibre utilization and cell cycle control. Thus, raw fibre utilization by the gut microbiome was guaranteed during the nutrient-deficient leaf stage by reinforcing gut microbiome robustness. During the protein-abundant shoot stage, the functional capacity of the gut microbiome expanded to include prokaryotic secretion and signal transduction activity, suggesting active interactions between the gut microbiome and host. These results illustrate that seasonal nutrient variation in wild giant pandas substantially influences gut microbiome composition and function. Nutritional interactions between gut microbiomes and hosts appear to be complex and further work is needed.

scholarly journals Development of the Gut Microbiome in Children, and Lifetime Implications for Obesity and Cardiometabolic Disease

Children ◽  
2018 ◽  
Vol 5 (12) ◽  
pp. 160 ◽  
Author(s):  
Anica I. Mohammadkhah ◽  
Eoin B. Simpson ◽  
Stephanie G. Patterson ◽  
Jane F. Ferguson
Keyword(s):  
Metabolic Disease ◽  
Gut Microbiome ◽  
Cardiometabolic Risk ◽  
Microbial Colonization ◽  
Cardiometabolic Disease ◽  
Metabolic Dysfunction ◽  
Microbiome Composition ◽  
Infancy And Childhood ◽  
Potential Impact ◽  
And Function

Emerging evidence suggests that microbiome composition and function is associated with development of obesity and metabolic disease. Microbial colonization expands rapidly following birth, and microbiome composition is particularly variable during infancy. Factors that influence the formation of the gut microbiome during infancy and childhood may have a significant impact on development of obesity and metabolic dysfunction, with life-long consequences. In this review, we examine the determinants of gut microbiome composition during infancy and childhood, and evaluate the potential impact on obesity and cardiometabolic risk.

scholarly journals Iron Biofortified Carioca Bean (Phaseolus vulgaris L.)—Based Brazilian Diet Delivers More Absorbable Iron and Affects the Gut Microbiota In Vivo (Gallus gallus)

Nutrients ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 1970 ◽  
Author(s):  
Desirrê Dias ◽  
Nikolai Kolba ◽  
Dana Binyamin ◽  
Oren Ziv ◽  
Marilia Regini Nutti ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Gallus Gallus ◽  
Bacterial Populations ◽  
Microbiome Composition ◽  
Treatment Groups ◽  
Micronutrient Concentration ◽  
Total Body ◽  
And Function

Biofortification aims to improve the micronutrient concentration and bioavailability in staple food crops. Unlike other strategies utilized to alleviate Fe deficiency, studies of the gut microbiota in the context of Fe biofortification are scarce. In this study, we performed a 6-week feeding trial in Gallus gallus (n = 15), aimed to investigate the Fe status and the alterations in the gut microbiome following the administration of Fe-biofortified carioca bean based diet (BC) versus a Fe-standard carioca bean based diet (SC). The tested diets were designed based on the Brazilian food consumption survey. Two primary outcomes were observed: (1) a significant increase in total body Hb-Fe values in the group receiving the Fe-biofortified carioca bean based diet; and (2) changes in the gut microbiome composition and function were observed, specifically, significant changes in phylogenetic diversity between treatment groups, as there was increased abundance of bacteria linked to phenolic catabolism, and increased abundance of beneficial SCFA-producing bacteria in the BC group. The BC group also presented a higher intestinal villi height compared to the SC group. Our results demonstrate that the Fe-biofortified carioca bean variety was able to moderately improve Fe status and to positively affect the intestinal functionality and bacterial populations.

scholarly journals Supplementation of Geranylgeraniol and Tocotrienols to High-Fat Diet Shifts the Gut Microbiome Composition and Function in Type 2 Diabetic Mice

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 393-393
Author(s):  
Moamen Elmassry ◽  
Eunhee Chung ◽  
Abdul Hamood ◽  
Chwan-Li Shen
Keyword(s):  
Relative Abundance ◽  
Gut Microbiome ◽  
High Fat Diet ◽  
Alpha Diversity ◽  
Control Group ◽  
Rrna Gene ◽  
High Fat ◽  
Microbiome Composition ◽  
And Function

Abstract Objectives In recent years, characterization of gut microbiota composition and function were linked to the progression of type 2 diabetes mellitus. Recent evidence showed that Geranylgeraniol, an isoprenoid found in fruits, vegetables, and grains, improves glucose homeostasis. Similarly, Tocotrienols, a subfamily of vitamin E, also contains anti-diabetic properties. In this study, we examined the combined effect of geranylgeraniol and tocotrienols on the composition and function of gut microbiome in obese male mice. Methods Forty male C57BL/6J mice were assigned to 4 groups in a factorial design as follows: high-fat diet (HFD) (control group), HFD + geranylgeraniol [400 mg/kg diet] (GG group), HFD + tocotrienols [400 mg/kg diet] (TT group), and HFD + geranylgeraniol + tocotrienols (G + T group) for 14 weeks. 16S rRNA gene sequencing was done from cecal samples and microbiome and data analysis was performed with QIIME2 and PICRUSt2. Results Across all groups, the most abundant phyla were Verrucomicrobia, Firmicutes, Bacteroidetes, and Actinobacteria. There was no difference in alpha diversity among different groups. Different treatments influenced the relative abundance of certain bacteria. In the Bacteroidetes phylum, the relative abundance of family S24–7 increased in the TT group only. In the Firmicutes phylum, the relative abundance of family Lachnospiraceae was reduced upon the supplementation of geranylgeraniol or tocotrienols; individually or in combination. In Verrucomicrobia phylum, Akkermansia muciniphila relative abundance was reduced in the TT group but increased in the G + T group. The results of functional profiling of the gut microbiome revealed that geranylgeraniol supplementation caused an increase in the proportion of biosynthetic pathways related to purine, pyrimidine, and inosine-5’-phosphate and hexitol fermentation, and a decrease in the proportion of pathways involved in the biosynthesis of isoleucine, valine, histidine, arginine, and chorismate. The G + T group increased pathways related to thiamine diphosphate biosynthesis, and decreased others involved into sulfur oxidation and methylerythritol phosphate. Conclusions The influence of geranylgeraniol and tocotrienols supplementation on gut microbiome composition and function, suggests a prebiotic potential for the potential of geranylgeraniol and tocotrienols. Funding Sources American River Nutrition, LLC, Hadley, MA.

scholarly journals Gut microbiome composition and function in experimental colitis during active disease and treatment-induced remission

2014 ◽  
Vol 8 (7) ◽  
pp. 1403-1417 ◽  
Author(s):  
Michelle G Rooks ◽  
Patrick Veiga ◽  
Leslie H Wardwell-Scott ◽  
Timothy Tickle ◽  
Nicola Segata ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Experimental Colitis ◽  
Microbiome Composition ◽  
And Function ◽  
Active Disease

scholarly journals The Western Dietary Pattern Combined with Vancomycin-Mediated Changes to the Gut Microbiome Exacerbates Colitis Severity and Colon Tumorigenesis

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 881
Author(s):  
Niklas D. Aardema ◽  
Daphne M. Rodriguez ◽  
Arnaud J. Van Wettere ◽  
Abby D. Benninghoff ◽  
Korry J. Hintze
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiome ◽  
Tumor Development ◽  
Alpha Diversity ◽  
Basal Diet ◽  
Plain Water ◽  
Microbiome Composition ◽  
Colon Tumorigenesis ◽  
Induced Changes ◽  
The Impact

Previous work by our group using a mouse model of inflammation-associated colorectal cancer (CAC) showed that the total Western diet (TWD) promoted colon tumor development. Others have also shown that vancomycin-mediated changes to the gut microbiome increased colorectal cancer (CRC). Therefore, the objective of this study was to determine the impact of vancomycin on colon tumorigenesis in the context of a standard mouse diet or the TWD. A 2 × 2 factorial design was used, in which C57Bl/6J mice were fed either the standard AIN93G diet or TWD and with vancomycin in the drinking water or not. While both the TWD and vancomycin treatments independently increased parameters associated with gut inflammation and tumorigenesis compared to AIN93G and plain water controls, mice fed the TWD and treated with vancomycin had significantly increased tumor multiplicity and burden relative to all other treatments. Vancomycin treatment significantly decreased alpha diversity and changed the abundance of several taxa at the phylum, family, and genus levels. Conversely, basal diet had relatively minor effects on the gut microbiome composition. These results support our previous research that the TWD promotes colon tumorigenesis and suggest that vancomycin-induced changes to the gut microbiome are associated with higher tumor rates.

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